Science.gov

Sample records for female fabry patients

  1. X-chromosome inactivation in female patients with Fabry disease.

    PubMed

    Echevarria, L; Benistan, K; Toussaint, A; Dubourg, O; Hagege, A A; Eladari, D; Jabbour, F; Beldjord, C; De Mazancourt, P; Germain, D P

    2016-01-01

    Fabry disease (FD) is an X-linked genetic disorder caused by the deficient activity of lysosomal α-galactosidase (α-Gal). While males are usually severely affected, clinical presentation in female patients may be more variable ranging from asymptomatic to, occasionally, as severely affected as male patients. The aim of this study was to evaluate the existence of skewed X-chromosome inactivation (XCI) in females with FD, its concordance between tissues, and its contribution to the phenotype. Fifty-six females with FD were enrolled. Clinical and biological work-up included two global scores [Mainz Severity Score Index (MSSI) and DS3], cardiac magnetic resonance imaging, measured glomerular filtration rate, and measurement of α-Gal activity. XCI was analyzed in four tissues using DNA methylation studies. Skewed XCI was found in 29% of the study population. A correlation was found in XCI patterns between blood and the other analyzed tissues although some punctual variability was detected. Significant differences in residual α-Gal levels, severity scores, progression of cardiomyopathy and deterioration of kidney function, depending on the direction and degree of skewing of XCI were evidenced. XCI significantly impacts the phenotype and natural history of FD in females.

  2. Histopathological evidence of Fabry disease in a female patient with left ventricular noncompaction.

    PubMed

    Martins, Elisabete; Pinho, Teresa; Carpenter, Stirling; Leite, Sérgio; Garcia, Raquel; Madureira, António; Oliveira, João Paulo

    2014-09-01

    Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the alpha-galactosidase gene. The most frequent cardiac presentation of Fabry disease is cardiomyopathy characterized by left ventricular (LV) hypertrophy, usually concentric. Heart disease in affected females tends to be clinically recognized later than in males and cardiac complications are the most frequently reported cause of death in females with Fabry disease. There are few data regarding the association between Fabry disease and LV noncompaction. We report a case of a 30-year-old asymptomatic woman, heterozygous for a nonsense alpha-galactosidase gene mutation (p.R220X), who presented LV noncompaction on cardiac magnetic resonance imaging, without LV wall hypertrophy. Histopathological examination of myocardial fragments showed marked deposition of glycosphingolipids in cardiomyocytes, confirming the diagnosis of Fabry cardiomyopathy. Based on this finding, the patient was proposed for enzyme replacement therapy. This case illustrates the role of endomyocardial biopsy in the clarification of doubtful or atypical findings related to cardiac Fabry disease, even in heterozygous women, and corroborates the contention that Fabry disease should be included in the differential diagnosis of LV hypertrabeculation/noncompaction.

  3. A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy

    PubMed Central

    Kistler, Andreas D.; Siwy, Justyna; Breunig, Frank; Jeevaratnam, Praveen; Scherl, Alexander; Mullen, William; Warnock, David G.; Wanner, Christoph; Hughes, Derralynn A.; Mischak, Harald; Wüthrich, Rudolf P.; Serra, Andreas L.

    2011-01-01

    Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naïve female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naïve Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy. PMID:21698285

  4. The ratio of alpha-galactosidase to beta-glucuronidase activities in dried blood for the identification of female Fabry disease patients.

    PubMed

    Lukacs, Z; Keil, A; Kohlschütter, A; Beck, M; Mengel, E

    2005-01-01

    Female heterozygous patients with Fabry disease are difficult to identify because of the relatively high residual activity of alpha-galactosidase. We systematically evaluated the activities of various lysosomal enzymes in dried blood samples from Fabry patients and found that the beta-glucuronidase activity was frequently elevated. The ratio of alpha-galactosidase to beta-glucuronidase proved to be a helpful tool for the diagnosis of female Fabry disease patients.

  5. Frequency of Fabry disease in male and female haemodialysis patients in Spain

    PubMed Central

    2010-01-01

    Background Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme α-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression. Methods A combined enzymatic and genetic strategy was used, measuring the activity of α-galactosidase A and genotyping the α-galactosidase A gene (GLA) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain. Results GLA alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with GLA causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients. Conclusions Excluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy. PMID:20122163

  6. [Females with Fabry's disease - an interdisciplinary diagnostic and therapeutic challenge].

    PubMed

    Weidemann, Frank; Niemann, Markus; Sommer, Claudia; Beer, Meinrad; Breunig, Frank; Wanner, Christoph

    2010-09-01

    Fabry's disease is a rare genetic storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of various organs. Being X-chromosomal-linked, most studies in the past focused on involvement in male patients. However, it has been elucidated recently that female patients can present typical organ involvement and, thus, have to be treated respectively. This synopsis wants to systematically review the typical organ involvement in female Fabry patients. Moreover, therapy recommendations especially for female patients are discussed.

  7. [Hearing loss in patients with Fabry disease].

    PubMed

    Limberger, A; Beck, M; Delgado-Sanchez, S; Keilmann, A

    2007-03-01

    Fabry disease is an X-linked lysosomal storage disease involving deficient activity of alpha-galactosidase A, which leads initially to pain, and later to renal insufficiency, cardiomyopathy and stroke. Until now few details are available on hearing impairment in patients with Fabry disease, and especially few relating to female patients. We examined 43 female and 29 male patients. In this study we looked into the question of whether and to what extent patients of both genders are affected by hearing impairment. Hearing loss is characteristic being more severe at high frequencies frequencies. Overall, 22 female and 15 male patients were found to have suffered a hearing loss. Patients with severe symptoms of Fabry disease usually demonstrate more prominent hearing losses. Both men and women with Fabry disease are affected by hearing impairment. It seems that the hearing loss is less marked in female than in male patients. Children with Fabry disease complain of tinnitus more frequently than other children and quite early in the course of the disease.

  8. Kidney transplantation in patients with Fabry disease.

    PubMed

    Cybulla, Markus; Walter, Kerstin Nanette; Schwarting, Andreas; Divito, Raffaelle; Feriozzi, Sandro; Sunder-Plassmann, Gere

    2009-04-01

    Little is known about the effects of enzyme replacement therapy (ERT) in kidney transplant recipients with Fabry disease. Clinical characteristics of transplant recipients in the Fabry Outcome Survey (FOS) were therefore examined in patients with Fabry disease with or without ERT. Of the 837 European patients in FOS (March 2006), 34 male patients and two female patients had received kidney transplants. Mean age at transplantation was 37.6 +/- 10.9 years, mean time since transplantation was 7.7 +/- 6.4 years, median estimated glomerular filtration rate (eGFR) was 44.4 ml/min/1.73 m(2), and median proteinuria was 296 mg/24 h. Of 27 patients with baseline data, 59% had hypertension, 74% had left ventricular hypertrophy, 22% had cardiac valve disease, 30% had arrhythmia, and 22% had transient ischaemic attacks and 15% stroke. Twenty patients (74%; two female patients, 18 male patients) were receiving ERT with agalsidase alfa. At enrollment or at the start of ERT, median eGFRs were 59 and 35 ml/min/1.73 m(2) (P = 0.05) and median proteinuria levels were 240 and 420 mg/24 h (not significant) in treated and untreated patients respectively. Renal function remained stable in patients receiving ERT. In conclusion, agalsidase alfa is well tolerated in patients with Fabry disease who have undergone renal transplantation.

  9. The severe clinical phenotype for a heterozygous Fabry female patient correlates to the methylation of non-mutated allele associated with chromosome 10q26 deletion syndrome.

    PubMed

    Hossain, Mohammad Arif; Yanagisawa, Hiroko; Miyajima, Takashi; Wu, Chen; Takamura, Ayumi; Akiyama, Keiko; Itagaki, Rina; Eto, Kaoru; Iwamoto, Takeo; Yokoi, Takayuki; Kurosawa, Kenji; Numabe, Hironao; Eto, Yoshikatsu

    2017-03-01

    Heterozygous Fabry females usually have an attenuated form of Fabry disease, causing them to be symptomatic; however, in rare cases, they can present with a severe phenotype. In this study, we report on a 37-year-old woman with acroparesthesia, a dysmorphic face, left ventricular hypertrophy, and intellectual disability. Her father had Fabry disease and died due to chronic renal and congestive cardiac failure. Her paternal uncle had chronic renal failure and intellectual disability, and her paternal aunt was affected with congestive cardiac failure. The patient has two sisters with no significant medical illness. However, her nephew has acroparesthesia, anhidrosis, and school phobia, and her niece shows mild phenotypes. The patient's enzyme analysis showed very low α-galactosidase A (α-gal A) activity in dried blood spot (DBS), lymphocytes, and skin fibroblasts with massive excretion of Gb3 and Gb2 in urine and lyso-Gb3 in DBS and plasma. Electron microscopic examination showed a large accumulation of sphingolipids in vascular endothelial cells and keratinocytes. Chromosomal analysis and comparative genomic hybridization microarray showed 10q26 terminal deletion. Molecular data showed a novel heterozygous stop codon mutation in exon 1 of the GLA gene in her sisters and niece, and a hemizygous state in her nephew. When we checked the methylation status, we found her non-mutated allele in the GLA gene was methylated. However, the non-mutated alleles of her sisters were non-methylated, and those of her niece were partially methylated. The chromosomal and methylation study may speculate the severity of her clinical phenotypes.

  10. [Cardiological follow-up in patients with Fabry disease].

    PubMed

    Pieruzzi, Federico; Pieroni, Maurizio; Chimenti, Cristina; Frustaci, Andrea; Sarais, Cristiano; Cecchi, Franco

    2010-01-01

    Fabry disease is a rare tesaurismosis due to a deficit of the lysosomal enzyme activity of alpha-galactosidase, needed for the normal catabolism of globotriaosylceramides (GL3). Fabry cardiac involvement has several clinical manifestations: concentric left ventricular hypertrophy without left ventricular dilation and severe loss of left ventricular systolic function, mitral and aortic valvulopathy, disorders of the atrioventricular conduction or repolarization, and compromised diastolic function. Differentiating Fabry disease from similar conditions is often quite straightforward, e.g., cardiac amyloidosis is often associated with low electrocardiographic voltages, and systemic symptoms are usually associated with hemochromatosis and sarcoidosis. However, sometimes second-level (genetic analysis, alpha-galactosidase levels) or invasive investigations are required, which can include endomyocardial biopsy. Diagnostic imaging techniques have been described, but they lack specificity. Echocardiographic imaging with tissue Doppler analysis and/or strain rate analysis can allow diagnosis of Fabry disease even before left ventricular hypertrophy becomes apparent. This review illustrates the techniques for staging cardiac involvement and damage in Fabry disease and for the long-term follow-up of Fabry patients with or without cardiac involvement. Careful cardiac monitoring is especially important in elderly female carriers, who often develop renal disorders and/or left ventricular hypertrophy as the only manifestations of their late Fabry disease. In some clinical series, Fabry disease was diagnosed in 12% of women with adult-onset hypertrophic cardiomyopathy. Cardiological problems and outcomes of enzyme replacement therapy, associated with or without other cardiological treatments, are also discussed.

  11. Fabry disease: experience of screening dialysis patients for Fabry disease.

    PubMed

    Kusano, Eiji; Saito, Osamu; Akimoto, Tetsu; Asano, Yasushi

    2014-04-01

    The prevalence rate for Fabry disease is conventionally considered to be 1 case in 40,000; however, due to increased screening accuracy, reports now suggest that prevalence is 1 case in 1,500 among male children, and it is likely that the clinical importance of the condition will increase in the future. In dialysis patients to date, prevalence rates are between 0.16 and 1.2 %. Globotriaosylsphingosine (Lyso-GL-3), which is a substrate of α-galactosidase A (α-Gal A), has surfaced as a new biomarker, and is also effective in the determination and monitoring of the effects of enzyme replacement therapy. In terms of genetic abnormalities, the E66Q mutation has recently become a topic of discussion, and although doubts have been expressed over whether or not it is the gene responsible for Fabry disease, there is still a strong possibility that it is a functional genetic polymorphism. At present, the standard treatment for Fabry disease is enzyme replacement therapy, and in order to overcome the problems involved with this, a method of producing recombinant human α-Gal A using methanol-assimilating yeast, and chemical or medicinal chaperone treatment are of current interest. Migalastat hydrochloride is known as a pharmacological chaperone, but is currently in Phase III global clinical trials. Adding saposin B to modified α-N-acetyl galactosaminidase is also under consideration as a treatment method.

  12. [Evaluation of patients with Fabry disease in Argentina].

    PubMed

    2010-01-01

    Fabry disease is an X- linked lysosomal disorder due to deficient activity of the enzyme alpha galactosidase A which leads to multisystemic storage of globotriaosylceramide with neurologic, gastrointestinal, cardiac, renal, skin and ophtalmological involvement. Recent studies indicate that heterozygous females develop symptoms similar to the males, but comparative information regarding the relative frequency of clinical manifestations, age of onset and severity of the disorder between males and females with Fabry disease is not available in Argentina. We identified 59 symptomatic adult patients with Fabry disease: 32 males (mean age 34.8 years) and 27 females (mean age 46.6 years). Diagnosis was made by enzymatic analysis in males and by genetic studies in females. We compared the frequency and severity of the clinical manifestations in females and males with this disease. The most frequent manifestations were: acroparesthesias, angiokeratomas, hypohydrosis (all them were significantly more frequent in males than in females, as well as the severity of symptoms), and cornea verticillata. Proteinuria and ventricular hypertrophy were frequent findings both in males and females. There was a delayed latency between age at onset and age at diagnosis in our group: 14 years for men and 30 years for females. Fabry disease is an underdiagnosed and potentially fatal disorder that affects both sexes. The availability of enzyme replacement therapy should stimulate the identification of signs and symptoms suggestive of this disorder, to allow earlier diagnosis and treatment.

  13. Identification of mutations in Colombian patients affected with Fabry disease.

    PubMed

    Uribe, Alfredo; Mateus, Heidi Eliana; Prieto, Juan Carlos; Palacios, Maria Fernanda; Ospina, Sandra Yaneth; Pasqualim, Gabriela; da Silveira Matte, Ursula; Giugliani, Roberto

    2015-12-15

    Fabry Disease (FD) is an X-linked inborn error of glycosphingolipid catabolism, caused by a deficiency of the lisosomal α-galactosidase A (AGAL). The disorder leads to a vascular disease secondary to the involvement of kidney, heart and the central nervous system. The mutation analysis is a valuable tool for diagnosis and genetic counseling. Although more than 600 mutations have been identified, most mutations are private. Our objective was to describe the analysis of nine Colombian patients with Fabry disease by automated sequencing of the seven exons of the GLA gene. Two novel mutations were identified in two patients affected with the classical subtype of FD, in addition to other 6 mutations previously reported. The present study confirms the heterogeneity of mutations in Fabry disease and the importance of molecular analysis for genetic counseling, female heterozygotes detection as well as therapeutic decisions. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Fabry disease in Argentina: an evaluation of patients enrolled in the Fabry Registry.

    PubMed

    Politei, J M; Cabrera, G; Amartino, H; Valdez, R; Masllorens, F; Ripeau, D; Antongiovanni, N; Soliani, A; Luna, P; Cedrolla, M; Fernandez, S; Fainboim, A

    2013-01-01

    Fabry disease (FD) is an X-linked inborn error of metabolism caused by alpha-galactosidase A deficiency. The Fabry Registry is an ongoing, global observational database that compiles clinical data from patients with FD. Demographic and baseline clinical characteristics of Fabry Registry patients enrolled in Argentina were analysed and compared with patients enrolled in the rest of the world (ROW). Baseline clinical parameters included chronic kidney disease (CKD) stage, urine protein-to-creatinine ratio and left ventricular posterior wall thickness. Only data from untreated patients were included. As of 1 October 2010, 3752 patients were enrolled in the Registry, 70 patients from Argentina and 3682 from the ROW. Argentinean male subjects were younger than Fabry Registry male subjects enrolled in ROW: mean current age 32.5 years vs. 39.0 years for men (p = 0.0257 by t-test). The current age (mean ± standard deviation) of female subjects enrolled in Argentina was not significantly different from that of female subjects enrolled in the ROW: 40.1 ± 17.28 vs. 43.2 ±17.95 years respectively (p = 0.2967). Overall, a smaller percentage of patients from Argentina received ERT compared with patients in the ROW (54% vs. 58% respectively). When evaluated by gender, more men and fewer women in Argentina received ERT compared with ROW (85% vs. 79% for men and 27% vs. 38% for women). A larger proportion of patients in ROW had severe CKD (stage 4 or 5) compared with Argentina (9.8% vs. 0%), most likely because of the older age of the ROW population. The enrolment of Argentinean patients into the Fabry Registry has steadily increased, as has the inclusion of female and paediatric patients with FD. The medical community in Argentina should be aware of FD in these populations, as awareness will facilitate prompt diagnosis and initiation of treatment, thus leading to improved outcomes. © 2012 Blackwell Publishing Ltd.

  15. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry.

    PubMed

    Wilcox, William R; Oliveira, João Paulo; Hopkin, Robert J; Ortiz, Alberto; Banikazemi, Maryam; Feldt-Rasmussen, Ulla; Sims, Katherine; Waldek, Stephen; Pastores, Gregory M; Lee, Philip; Eng, Christine M; Marodi, Laszlo; Stanford, Kevin E; Breunig, Frank; Wanner, Christoph; Warnock, David G; Lemay, Roberta M; Germain, Dominique P

    2008-02-01

    Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A deficiency. The Fabry Registry is a global clinical effort to collect longitudinal data on FD. In the past, most "carrier" females were usually thought to be clinically unaffected. A systematic effort has been made to enroll all FD females, regardless of symptomology. Of the 1077 enrolled females in the Registry, 69.4% had symptoms and signs of FD. The median age at symptom onset among females was 13 years, and even though 84.1% had a positive family history, the diagnosis was not made until a median age of 31 years. Twenty percent experienced major cerebrovascular, cardiac, or renal events, at a median age of 46 years. Among adult females with estimated glomerular filtration rate (eGFR) data (N=638), 62.5% had an eGFR <90 ml/min/1.73 m2 and 19.0% had eGFR <60 ml/min/1.73 m2. Proteinuria 300 mg/day was present in 39.0% of females, and 22.2% had >1 gram/day. Quality of life (QoL), as measured by the SF-36((R)) survey, was impaired at a later age than in males, but both genders experience significantly impaired QoL from the third decade of life onward. Thus, females with FD have a significant risk for major organ involvement and decreased QoL. Females should be regularly monitored for signs and symptoms of FD, and considered for enzyme replacement therapy.

  16. [Fabry disease: An overlooked diagnosis in adult cardiac patients].

    PubMed

    Kayıkçıoğlu, Meral; Şimşek, Evrim; Kalkan Uçar, Sema; Bayraktaroğlu, Selen; Onay, Hüseyin; Sözmen, Eser; Çoker, Mahmut

    2017-09-01

    Fabry disease is a rare, X-linked, lysosomal glycosphingolipid storage disorder. A deficiency of the enzyme alpha-galactosidase results in intracellular accumulation of globotriaosylceramide in multiple cell types, such as those of the nerves, kidneys, cardiac, and cutaneous tissues, leading to a multisystem disease. Male patients are more severely affected; however, heterozygous female patients may also be afflicted, though often the symptoms develop later. Cardiac involvement can include left ventricular hypertrophy, conduction abnormalities, arrhythmias, valvular abnormalities, and heart failure. A variant of the disease affects only cardiac tissue and mostly manifests as unexplained ventricular hypertrophy. Presently described are 2 cases of Fabry disease and the signs and symptoms of cardiac involvement, as well as the importance of early diagnosis to start enzyme replacement therapy before the development of irreversible tissue damage.

  17. Hormonal profile and fertility in patients with Anderson-Fabry disease.

    PubMed

    Hauser, A C; Gessl, A; Harm, F; Wiesholzer, M; Kleinert, J; Wallner, M; Voigtländer, T; Bieglmayer, C; Sunder-Plassmann, G

    2005-09-01

    Anderson-Fabry disease is a glycosphingolipid storage disorder with an X-linked recessive inheritance. The alpha-galactosidase A deficiency leads to a progressive accumulation of globotriaosylceramide in the endothelium and tissue cells of various organs. The kidney, heart and brain are predominantly affected. Reports on endocrine function and fertility rates in patients with Anderson-Fabry disease are sparse. In the present study, we assessed ovarian, testicular and adrenal function in a cohort of patients with Anderson-Fabry disease. Plasma follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, sex hormone-binding globulin, somatotropin, insulin-like growth factor-I and serum cortisol were measured in 13 patients (six female and seven male), currently observed in an outpatient clinic. The profile revealed an undisturbed hormonal function and a normal fertility rate in both male and female Anderson-Fabry patients when compared with the corresponding Austrian population.

  18. A comprehensive Fabry-related pain questionnaire for adult patients.

    PubMed

    Üçeyler, Nurcan; Magg, Barbara; Thomas, Phillip; Wiedmann, Silke; Heuschmann, Peter; Sommer, Claudia

    2014-11-01

    Pain may be the earliest symptom in Fabry disease and presents with a distinct phenotype including triggerable pain attacks, evoked pain, pain crises, and chronic pain. Current pain questionnaires do not reflect the special phenotype of Fabry disease-associated pain, which hampers its systematic evaluation as the basis of correct diagnosis and effective treatment. A questionnaire specifically designed to assess Fabry disease-associated pain is thus urgently needed. At the Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), Germany, we developed and validated the first face-to-face Fabry Pain Questionnaire (FPQ) for adult patients. The initial version of the FPQ was tested in a pilot study with 20 consecutive Fabry disease patients. The performance of the revised FPQ was assessed in a first (n=56) and second (n=20) validation phase in consecutive Fabry disease patients. For this, patients were interviewed at baseline and 2 weeks later. We determined the test-retest reliability and validity of the FPQ in comparison to data obtained with the Neuropathic Pain Symptom Inventory. The FPQ contains 15 questions on the 4 pain phenotypes of Fabry disease (pain attacks, pain crises, evoked pain, chronic pain) in childhood and adulthood, on pain development during life with and without enzyme replacement therapy, and on everyday life impairment due to pain. This first disease-specific questionnaire is a valuable tool for baseline and follow-up assessment of pain in Fabry disease patients and may guide treatment in this distinct pain phenotype.

  19. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

    PubMed Central

    Fall, Brent; Scott, C. Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A.; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value. PMID:27992580

  20. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy.

    PubMed

    Fall, Brent; Scott, C Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value.

  1. Cerebral hemodynamics and endothelial function in patients with Fabry disease.

    PubMed

    Segura, Tomás; Ayo-Martín, Oscar; Gómez-Fernandez, Isabel; Andrés, Carolina; Barba, Miguel A; Vivancos, José

    2013-11-11

    Cerebral vasculopathy have been described in Fabry disease, in which altered cerebral blood flow, vascular remodelling or impairment of endothelial function could be involved. Our study aims to evaluate these three possibilities in a group of Fabry patients, and compare it to healthy controls. Cerebral hemodynamics, vascular remodelling and systemic endothelial function were investigated in 10 Fabry patients and compared to data from 17 healthy controls. Transcranial Doppler was used to study blood flow velocity of intracranial arteries and cerebral vasomotor reactivity. For the study of vascular remodelling and endothelial function, intima-media thickness of common carotid arteries, flow-mediated dilation in brachial artery and serum levels of soluble VCAM-1, TNF-α, high-sensitive CRP and IL-6 were measured. Differences between groups were evaluated using appropriate tests. No relevant differences were observed in cerebral hemodynamic parameters, intima-media thickness or flow-mediated dilation. There was a trend for low serum levels of IL-6 and high serum levels of TNF-α and high-sensitive CRP in Fabry patients; plasma concentrations of soluble VCAM-1 were significantly higher in Fabry disease patients than in healthy volunteers (p = 0.02). In our sample, we did not find relevant alterations of cerebral hemodynamics in Fabry disease patients. Increased levels of plasmatic endothelial biomarkers seem to be the most important feature indicative of possible vascular dysfunction in Fabry disease patients.

  2. Cerebral hemodynamics and endothelial function in patients with Fabry disease

    PubMed Central

    2013-01-01

    Background Cerebral vasculopathy have been described in Fabry disease, in which altered cerebral blood flow, vascular remodelling or impairment of endothelial function could be involved. Our study aims to evaluate these three possibilities in a group of Fabry patients, and compare it to healthy controls. Methods Cerebral hemodynamics, vascular remodelling and systemic endothelial function were investigated in 10 Fabry patients and compared to data from 17 healthy controls. Transcranial Doppler was used to study blood flow velocity of intracranial arteries and cerebral vasomotor reactivity. For the study of vascular remodelling and endothelial function, intima-media thickness of common carotid arteries, flow-mediated dilation in brachial artery and serum levels of soluble VCAM-1, TNF-α, high-sensitive CRP and IL-6 were measured. Differences between groups were evaluated using appropriate tests. Results No relevant differences were observed in cerebral hemodynamic parameters, intima-media thickness or flow-mediated dilation. There was a trend for low serum levels of IL-6 and high serum levels of TNF-α and high-sensitive CRP in Fabry patients; plasma concentrations of soluble VCAM-1 were significantly higher in Fabry disease patients than in healthy volunteers (p = 0.02). Conclusions In our sample, we did not find relevant alterations of cerebral hemodynamics in Fabry disease patients. Increased levels of plasmatic endothelial biomarkers seem to be the most important feature indicative of possible vascular dysfunction in Fabry disease patients. PMID:24207059

  3. Prevalence of Fabry disease and GLA c.196G>C variant in Japanese stroke patients.

    PubMed

    Nagamatsu, Kiyoshiro; Sekijima, Yoshiki; Nakamura, Katsuya; Nakamura, Kimitoshi; Hattori, Kiyoko; Ota, Masao; Shimizu, Yusaku; Endo, Fumio; Ikeda, Shu-Ichi

    2017-03-09

    Fabry disease is an important underlying disease in young cryptogenic stroke patients. However, little is known regarding the frequency of Fabry disease in the general stroke population, especially in elderly patients. A total of 588 stroke patients (61.7% men; average age 74.1±12.5 years) were enrolled in this prospective study. Blood samples were obtained to produce blood spots to determine α-galactosidase A (α-GalA) activity and for GLA gene analysis. One 65-year-old female patient had a known GLA gene mutation, c.2T>C (p.M1T), causing Fabry disease. Five male patients and two female patients had GLA c.196G>C (p.E66Q) variant, which is not associated with the full clinical manifestations of Fabry disease. The allele frequency of GLA c.196G>C was significantly higher in male patients with small-vessel occlusion (odds ratio 3.95, P=0.048) and non-cardioembolism (odds ratio 4.08, P=0.012) than that in the general Japanese population. Fabry disease is rare in the general Japanese stroke population. However, screening identified one elderly female patient with Fabry disease. GLA c.196G>C variant is a genetic risk factor for cerebral small-vessel occlusion and non-cardioembolism in Japanese males but not in females.Journal of Human Genetics advance online publication, 9 March 2017; doi:10.1038/jhg.2017.31.

  4. Identification of Fabry Disease in a Tertiary Referral Cohort of Patients with Hypertrophic Cardiomyopathy.

    PubMed

    Maron, Martin S; Xin, Winnie; Sims, Katherine B; Butler, Rita; Haas, Tammy S; Rowin, Ethan J; Desnick, Robert J; Maron, Barry J

    2017-09-21

    Fabry Disease is a X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase A due to mutations in the GLA gene, which may be associated with increased left ventricular wall thickness, and mimic the morphologic features of hypertrophic cardiomyopathy. Management strategies for these two diseases diverge, with Fabry disease-specific treatment utilizing recombinant α-galactosidase A enzyme replacement therapy. We studied a prospectively assembled consecutive cohort of 585 patients (71% male) from two hypertrophic cardiomyopathy tertiary referral centers by screening for low α-galactosidase A activity in dried blood spots. Male patients with low α -Gal A activity levels and all females were tested for mutations in the GLA gene. In 585 patients previously diagnosed with hypertrophic cardiomyopathy, we identified two unrelated patients (0.34%), both with the GLA mutation encoding P.N215S the most common mutation causing later-onset Fabry disease phenotype. These patients were both asymptomatic, a male age 53 years and a female aged 69 yearsand demonstrated a mild cardiac phenotype with symmetric distribution of left ventricular hypertrophy..Following family screening, a total of 27 new Fabry disease patients ages 2-81 years were identified in the two families, including 12individuals who are now receiving enzyme replacement therapy. These observations support consideration for routine prospective screening for Fabry disease in all patients without a definitive etiology for left ventriclar hypertrophy. This strategy would likely result, through cascade family testing, in the earlier identification of new Fabry disease-affected males and female heterozygotes who may benefit from monitoring and/or enzyme replacement therapy. Copyright © 2017. Published by Elsevier Inc.

  5. Functional and structural nerve fiber findings in heterozygote patients with Fabry disease.

    PubMed

    Torvin Møller, Anette; Winther Bach, Flemming; Feldt-Rasmussen, Ulla; Rasmussen, Ase; Hasholt, Lis; Lan, He; Sommer, Claudia; Kølvraa, Steen; Ballegaard, Martin; Staehelin Jensen, Troels

    2009-09-01

    Fabry disease is an X-linked inherited lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system. Pain and somatosensory disturbances are prominent manifestations of this disease. Until recently disease manifestations in female carriers of Fabry disease have been questioned. To explore the frequency of symptoms and the functional and structural involvement of the nervous system in female patients we examined the presence of pain, manifestations of peripheral neuropathy and nerve density in skin biopsies in 19 female patients with Fabry disease and 19 sex- and age-matched controls. Diaries, quantitative sensory testing, neurophysiologic tests and skin biopsies were performed. Daily pain was present in 63% of patients, with a median VAS score of 4.0. Tactile detection threshold and pressure pain threshold were lower and cold detection thresholds increased in patients. Sensory nerve action potential amplitude and maximal sensory conduction velocity were not different, whereas there was a highly significant reduction in intraepidermal nerve fiber density. We found no correlation between pain VAS score, quantitative sensory testing and intraepidermal nerve fiber density. Our study demonstrates that careful evaluation of symptoms in female Fabry patients is important as small fiber disease manifestations are present, which in some cases is only detected by skin biopsy.

  6. Biomolecules damage and redox status abnormalities in Fabry patients before and during enzyme replacement therapy.

    PubMed

    Biancini, Giovana Brondani; Jacques, Carlos Eduardo; Hammerschmidt, Tatiane; de Souza, Heryk Motta; Donida, Bruna; Deon, Marion; Vairo, Filippo Pinto; Lourenço, Charles Marques; Giugliani, Roberto; Vargas, Carmen Regla

    2016-10-01

    Fabry disease (FD) is caused by deficient activity of the lysosomal enzyme α-galactosidase A. Its substrates, mainly globotriaosylceramide (Gb3), accumulate and seem to induce other pathophysiological findings of FD. Once enzyme replacement therapy (ERT) is not completely efficient on preventing disease progress in FD patients, elucidating the underlying mechanisms in FD pathophysiology is essential to the development of additional therapeutic strategies. We investigated 58 Fabry patients (23 male and 35 female) subdivided into two groups (at diagnosis and during long-term ERT) and compared them to healthy individuals. Fabry patients at diagnosis presented altered glutathione (GSH) metabolism (higher GSH levels, lower glutathione peroxidase - GPx - and normal glutathione reductase - GR - activities), higher lipid peroxidation levels (thiobarbituric acid reactive species - TBARS - and malondialdehyde - MDA), nitric oxide (NO(.)) equivalents and urinary Gb3. Fabry patients on ERT presented GSH metabolism similar to controls, although lipid peroxidation and urinary levels of NO(.) equivalents remained higher whereas Gb3 levels were lower than at diagnosis but still higher than controls. These data demonstrated that redox impairment occurs in Fabry patients before and after ERT, probably as a consequence of Gb3 accumulation, providing targets to future therapy approaches using antioxidants in combination with ERT in FD.

  7. A survey of the pain experienced by males and females with Fabry disease

    PubMed Central

    Gibas, Andrea L; Klatt, Regan; Johnson, Jack; Clarke, Joe TR; Katz, Joel

    2006-01-01

    BACKGROUND The clinical onset of Fabry disease, a rare, X-linked, multisystemic disorder, is marked by neuropathic pain. Males suffer extensively from this disease. Females, as genetic ‘carriers’, have traditionally been viewed as either asymptomatic or mildly afflicted with this disease. OBJECTIVES To describe Fabry-related pain and compare experiences between the sexes. Patients’ perceptions of physician pain assessments were also examined. METHODS A disease-specific questionnaire was accessible on-line (www.fabry.org) and mailed to 552 members of a Fabry disease support group. RESULTS The response rate was 14.3% for the support group-based mail questionnaire. Females (58.0%) were significantly older (mean ± SD 45.9±13.5 years) than males (mean ± SD 40.0±12.1; t [86]=−2.11, P<0.05). Females were diagnosed with Fabry disease later (31.1±14.0 years) than males (24.2±11.9 years; t [86]=−2.43, P<0.05). Females (mean score for pain disability rating 3.0±1.4) suffered more extensive disability from migraine pain (mean score 2.2±1.3; F [1, 74]=45.0, P<0.005), and, unlike males, did not exhibit a decline in pain intensity with disease duration. Satisfaction with physician pain assessments was moderate. CONCLUSIONS Contrary to the traditional view of females as carriers, females with Fabry disease experienced intense disease-related pain; pain produced comparable distress and impairment in both sexes. The diagnostic delay and absence of a decline in pain symptoms over time in females suggest additional disease burden. Females may be triply disadvantaged in the health care system due to disease rarity, devalued carrier status and sex. PMID:16960635

  8. High prevalence of subclinical hypothyroidism in patients with Anderson-Fabry disease.

    PubMed

    Hauser, A C; Gessl, A; Lorenz, M; Voigtländer, T; Födinger, M; Sunder-Plassmann, G

    2005-01-01

    Anderson-Fabry disease is a rare lysosomal storage disorder. It results from a deficiency of the lysosomal alpha-galactosidase A and leads to progressive accumulation of globotriaosylceramide in the endothelium and tissue cells of various organs. Some of the typical clinical findings such as tiredness, dry skin, myalgia and arthralgia as well as vague gastrointestinal complaints are also symptoms of hypothyroidism. Therefore, we studied the thyroid function in patients with Anderson-Fabry disease. Thyroid function was studied in 11 patients (6 female, 5 male) with Anderson-Fabry disease by measuring thyroid-stimulating hormone (TSH) and free thyroxine serum levels. Nine patients had chronic kidney disease with stage 1 and two with stage 5. Subclinical hypothyroidism (normal serum free thyroxine concentrations along with elevated serum TSH levels) was found in 4 of 11 patients (36.4%). Subclinical hypothyroidism was observed in both male and female patients as well as in patients with stage 1 and stage 5 kidney disease. Subclinical hypothyroidism is a common finding in patients with Anderson-Fabry disease, showing an excess prevalence as compared to the normal population. The high frequency seems to be relevant regarding the potential consequences of a hypothyroid state.

  9. A Novel Rapid MALDI-TOF-MS-Based Method for Measuring Urinary Globotriaosylceramide in Fabry Patients

    NASA Astrophysics Data System (ADS)

    Alharbi, Fahad J.; Geberhiwot, Tarekegn; Hughes, Derralynn A.; Ward, Douglas G.

    2016-04-01

    Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, resulting in the accumulation of glycosphingolipids in various organs. Globotriaosylceramide (Gb3) and its isoforms and analogues have been identified and quantified as biomarkers of disease severity and treatment efficacy. The current study aimed to establish rapid methods for urinary Gb3 extraction and quantitation. Urine samples from 15 Fabry patients and 21 healthy control subjects were processed to extract Gb3 by mixing equal volumes of urine, methanol containing an internal standard, and chloroform followed by sonication and centrifugation. Thereafter, the lower phase was analyzed by MALDI-TOF MS and the relative peak areas of the internal standard and four major species of Gb3 determined. The results showed high reproducibility with intra- and inter-assay coefficients variation of 9.9% and 13.7%, respectively. The limit of detection was 0.15 ng/μL and the limit of quantitation was 0.30 ng/μL. Total urinary Gb3 levels in both genders of classic Fabry patients were significantly higher than in healthy controls (p < 0.0001). Gb3 levels in Fabry males were higher than in Fabry females (p = 0.08). We have established a novel assay for urinary total Gb3 that takes less than 15 min from start to finish.

  10. A Novel Rapid MALDI-TOF-MS-Based Method for Measuring Urinary Globotriaosylceramide in Fabry Patients.

    PubMed

    Alharbi, Fahad J; Geberhiwot, Tarekegn; Hughes, Derralynn A; Ward, Douglas G

    2016-04-01

    Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, resulting in the accumulation of glycosphingolipids in various organs. Globotriaosylceramide (Gb3) and its isoforms and analogues have been identified and quantified as biomarkers of disease severity and treatment efficacy. The current study aimed to establish rapid methods for urinary Gb3 extraction and quantitation. Urine samples from 15 Fabry patients and 21 healthy control subjects were processed to extract Gb3 by mixing equal volumes of urine, methanol containing an internal standard, and chloroform followed by sonication and centrifugation. Thereafter, the lower phase was analyzed by MALDI-TOF MS and the relative peak areas of the internal standard and four major species of Gb3 determined. The results showed high reproducibility with intra- and inter-assay coefficients variation of 9.9% and 13.7%, respectively. The limit of detection was 0.15 ng/μL and the limit of quantitation was 0.30 ng/μL. Total urinary Gb3 levels in both genders of classic Fabry patients were significantly higher than in healthy controls (p < 0.0001). Gb3 levels in Fabry males were higher than in Fabry females (p = 0.08). We have established a novel assay for urinary total Gb3 that takes less than 15 min from start to finish. Graphical Abstract ᅟ.

  11. Screening Fabry's disease in chronic kidney disease patients not on dialysis: a multicenter study.

    PubMed

    Yeniçerioğlu, Yavuz; Akdam, Hakan; Dursun, Belda; Alp, Alper; Sağlam Eyiler, Funda; Akın, Davut; Gün, Yelda; Hüddam, Bülent; Batmazoğlu, Mehmet; Gibyeli Genek, Dilek; Pirinççi, Serhat; Ersoy, İsmail Rıfkı; Üzüm, Atilla; Soypaçacı, Zeki; Tanrısev, Mehmet; Çolak, Hülya; Demiral Sezer, Sibel; Bozkurt, Gökay; Akyıldız, Utku Oğan; Akyüz Ünsal, Ayşe İpek; Ünübol, Mustafa; Uslu, Meltem; Eryılmaz, Ufuk; Günel, Ceren; Meteoğlu, İbrahim; Yavaşoğlu, İrfan; Ünsal, Alparslan; Akar, Harun; Okyay, Pınar

    2017-11-01

    Fabry's disease is an X-linked inherited, rare, progressive, lysosomal storage disorder, affecting multiple organs due to the deficient activity of α-galactosidase A (α-Gal A) enzyme. The prevalence has been reported to be 0.15-1% in hemodialysis patients; however, the information on the prevalence in chronic kidney disease not on dialysis is lacking. This study aimed to determine the prevalence of Fabry's disease in chronic kidney disease. The patients older than 18 years, enclosing KDIGO 2012 chronic kidney disease definitions, not on dialysis, were enrolled. Dried blood spots on Guthrie papers were used to analyze α-Gal A enzyme and genetic analysis was performed in individuals with enzyme activity ≤1.2 μmol/L/h. A total of 1453 chronic kidney disease patients not on dialysis from seven clinics in Turkey were screened. The mean age of the study population was 59.3 ± 15.9 years. 45.6% of patients were female. The creatinine clearance of 77.3% of patients was below 60 mL/min/1.73 m(2), 8.4% had proteinuria, and 2.5% had isolated microscopic hematuria. The mean value of patients' α-Gal A enzyme was detected as 2.93 ± 1.92 μmol/L/h. 152 patients had low levels of α-Gal A enzyme activity (≤1.2 μmol/L/h). In mutation analysis, A143T and D313Y variants were disclosed in three male patients. The prevalence of Fabry's disease in chronic kidney disease not on dialysis was found to be 0.2% (0.4% in male, 0.0% in female). Fabry's disease should be considered in the differential diagnosis of chronic kidney disease with unknown etiology even in the absence of symptoms and signs suggestive of Fabry's disease.

  12. Acute cerebrovascular disease in the young: the Stroke in Young Fabry Patients study.

    PubMed

    Rolfs, Arndt; Fazekas, Franz; Grittner, Ulrike; Dichgans, Martin; Martus, Peter; Holzhausen, Martin; Böttcher, Tobias; Heuschmann, Peter U; Tatlisumak, Turgut; Tanislav, Christian; Jungehulsing, Gerhard J; Giese, Anne-Katrin; Putaala, Jukaa; Huber, Roman; Bodechtel, Ulf; Lichy, Christoph; Enzinger, Christian; Schmidt, Reinhold; Hennerici, Michael G; Kaps, Manfred; Kessler, Christof; Lackner, Karl; Paschke, Eduard; Meyer, Wolfgang; Mascher, Hermann; Riess, Olaf; Kolodny, Edwin; Norrving, Bo

    2013-02-01

    Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov.Unique identifier: NCT00414583.

  13. Genomic analysis of Brazilian patients with Fabry disease.

    PubMed

    Pereira, F S; Jardim, L B; Netto, C B; Burin, M G; Cecchin, C; Giugliani, R; Matte, U S

    2007-12-01

    Fabry disease is an X-linked lysosomal disorder due to a-galactosidase A deficiency that causes storage of globotriaosylceramide. The gene coding for this lysosomal enzyme is located on the long arm of the X chromosome, in region Xq21.33-Xq22. Disease progression leads to vascular disease secondary to involvement of kidney, heart and the central nervous system. Detection of female carriers based solely on enzyme assays is often inconclusive. Therefore, mutation analysis is a valuable tool for diagnosis and genetic counseling. Many mutations of the a-galactosidase A gene have been reported with high genetic heterogeneity, being most mutations private found in only one family. The disease is panethnic, and estimates of incidence range from about 1 in 40,000 to 60,000 males. Our objective was to describe the analysis of 6 male and 7 female individuals belonging to 4 different Fabry disease families by automated sequencing of the seven exons of the alpha-galactosidase gene. Sequencing was performed using PCR fragments for each exon amplified from DNA extracted from peripheral blood. Three known mutations and one previously described in another Brazilian family were detected. Of 7 female relatives studied, 4 were carriers. Although the present study confirms the heterogeneity of mutations in Fabry disease, the finding of the same mutation previously detected in another Fabry family from our region raises the possibility of some founder effect, or genetic drift. Finally, the present study highlights the importance of molecular analysis for carrier detection and genetic counseling.

  14. The neurocognitive impact of Fabry disease on pediatric patients.

    PubMed

    Bugescu, Nicolle; Alioto, Andrea; Segal, Summer; Cordova, Matthew; Packman, Wendy

    2015-04-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder that results in progressive multisystemic organ complications. Several studies have examined neurocognitive impairments in adults; however, there is a paucity of research examining neurocognitive functioning in children with FD. This is the first exploratory study to examine the neurocognitive functioning of pediatric patients with FD and to evaluate the effects of enzyme replacement therapy (ERT) on neurocognitive functioning within this population. Families attending a national conference with at least one child with FD and one parent affected by FD comprised the sample (n = 48; 24 pediatric patients, 24 parents). Pediatric participants (10 males, 14 females) between the ages of 6 and 18 years and their parent(s) were involved in the study. Data from a demographic questionnaire and two neurocognitive self-report and parent-report measures were analyzed. Parent reports of neurocognitive functioning were also compared to a sample of children with and without head injury and to a sample of children who had undergone liver transplant (LT). Children with FD had poorer cognitive and executive functioning than healthy peers, and were comparable to children with head injury and LT. In addition, children using ERT had higher scores on measures of overall cognitive functioning, as well as fewer problems with attention/working memory and executive functioning. Results of this study suggest that children with FD may exhibit poorer cognitive and executive functioning relative to healthy peers. The use of ERT may mitigate the negative impact of FD on neurocognitive functioning in pediatric patients. © 2015 Wiley Periodicals, Inc.

  15. Preliminary Screening Results of Fabry Disease in Kidney Transplantation Patients: A Single-Center Study.

    PubMed

    Yılmaz, M; Uçar, S K; Aşçı, G; Canda, E; Tan, F A; Hoşcoşkun, C; Çoker, M; Töz, H

    2017-04-01

    Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of alfa-galactosidase A (AGALA) and leads to progressive impairment of renal function in almost all male patients and in a significant proportion of female patients. FD is underdiagnosed or even misdiagnosed in patients undergoing kidney transplantation. We initiated a selective screening study for FD among kidney transplant patients in our center. In this study, 1095 male and female patients were included. Dried blood samples on Guthrie papers were used to analyze galactosidase A enzyme for male patients. Genetic analyses were performed in all female and male patients with low enzyme activity. In total, 648 female and 447 male patients with functioning grafts were evaluated. Among 1095 patients, 5 male patients had AGALA activity below threshold and 3 female patients had galactosidase alpha gene DNA variations. One male patient had a disease-causing mutation. The other 4 patients had polymorphisms causing low enzyme activity. All the 3 female patients had mutations that were associated with FD according to Human Gene Mutation Database (ID: CM025441). In contrast, these mutations were reported as unknown clinical significance in Clinvar (rs149391489). The patients with clinical findings suggesting FD were planned to be analyzed for Lyso Gb3. In our selective screening study, 8 variations were found among 1095 kidney transplantation patients, which needs further investigation to determine causes of FD. Clinical findings, physical examination, and family history are also necessary to evaluate the genetic changes as a mutation in this selected population.

  16. Identification of a novel GLA mutation (F69 L) in a Japanese patient with late-onset Fabry disease.

    PubMed

    Umeda, Toshiko; Hashimoto, Seiji; Noriyasu, Kazuyuki; Takamura, Ayumi; Fujisaki, Miwa; Eto, Yoshikatsu

    2015-01-01

    Fabry disease is an X-linked recessive inborn error of glycosphingolipid catabolism caused by a mutation in the GLA gene. We sequenced the α-galactosidase A gene (GLA) of a patient who had been clinically diagnosed with late-onset Fabry disease. Abundant globotriaosylceramide was present in his urine, which indicated typical Fabry disease. Here, we report a novel hemizygous mutation, c.207C>A (Phe69 Leu), which caused a mild/late-onset form of Fabry disease.

  17. A male Fabry disease patient treated with intravenous thrombolysis for acute ischemic stroke.

    PubMed

    Saarinen, Jukka T; Sillanpää, Niko; Kantola, Ilkka

    2015-02-01

    The use of intravenous thrombolytic therapy for acute ischemic stroke is associated with improved outcomes. Fabry disease is an X-linked glycosphingolipid storage disease with vascular endothelial deposits. Affected males with the classic phenotype develop renal, cardiac, and cerebrovascular disease and die prematurely. However, Fabry disease is rare in young men with first ischemic stroke of undetermined cause. We report a 38-year-old man with acute aphasia and a left M2 segment of the middle cerebral artery thrombus with no recanalization who was finally diagnosed with Fabry disease after left ventricular hypertrophy of undetermined cause had been identified. A gene test revealed a R227X mutation typical of Fabry disease with the classical phenotype. To our knowledge our patient is the first reported male Fabry patient who was given intravenous thrombolytic therapy and the first reported Fabry patient who received intravenous thrombolytic therapy between 3 and 4.5 hours of the symptom onset. Despite favorable prognostic indicators on admission imaging, our patient suffered a significant stroke and had an unfavorable clinical outcome. Fortunately, the episode was not complicated by intracranial hemorrhage. Further studies are needed to evaluate the efficacy and safety of intravenous thrombolytic therapy in treating patients with Fabry disease and acute ischemic stroke.

  18. Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease.

    PubMed

    Najafian, Behzad; Svarstad, Einar; Bostad, Leif; Gubler, Marie-Claire; Tøndel, Camilla; Whitley, Chester; Mauer, Michael

    2011-03-01

    Progressive renal failure often complicates Fabry disease, the pathogenesis of which is not well understood. To further explore this we applied unbiased stereological quantitative methods to electron microscopic changes of Fabry nephropathy and the relationship between parameters of glomerular structure and renal function in 14 young Fabry patients (median age 12 years). Renal biopsies were obtained shortly before enzyme replacement therapy from these patients and from nine normal living kidney donors as controls. Podocyte globotriaosylceramide (GL-3) inclusion volume density increased progressively with age; however, there were no significant relationships between age and endothelial or mesangial inclusion volume densities. Foot process width, greater in male Fabry patients, also progressively increased with age compared with the controls, and correlated directly with proteinuria. In comparison to the biopsies of the controls, endothelial fenestration was reduced in Fabry patients. Thus, our study found relationships between quantitative parameters of glomerular structure in Fabry nephropathy and age, as well as urinary protein excretion. Hence, podocyte injury may play a pivotal role in the development and progression of Fabry nephropathy.

  19. Fabry in the older patient: Clinical consequences and possibilities for treatment.

    PubMed

    Lidove, Olivier; Barbey, Frédéric; Niu, Dau-Ming; Brand, Eva; Nicholls, Kathleen; Bizjajeva, Svetlana; Hughes, Derralynn A

    2016-08-01

    Baseline demographic and phenotypic characteristics of patients aged ≥50years in the Fabry Outcome Survey (Shire; data extracted June 2014) were compared with younger adults to investigate potential factors influencing treatment decisions in later life. Age groups were defined using age at treatment initiation or at FOS entry for untreated patients: 18-49 (n=1344; 49.5% male; 64.6% received agalsidase alfa enzyme replacement therapy [ERT]); 50-64 (n=537; 35.4% male; 74.3% treated); 65-74 (n=137; 32.1% male; 68.6% treated); and ≥75years (n=26; 26.9% male; 50.0% treated). Successive age groups showed higher median age at first symptom and diagnosis. Median alpha-galactosidase A activity, measured as percentage activity of the midpoint of the normal range, was much greater in females than males of all groups except ≥75years (33.4% in females; 27.8% in males). Patients aged ≥75years showed greater values than patients aged 18-49years for median left ventricular mass indexed to height (62.7 vs 42.4g/m(2.7)), mean ventricular wall thickness (15.0 vs 10.0mm) and prevalence of hypertension (57.7% vs 21.8%), and lower median estimated glomerular filtration rate (Modification of Diet in Renal Disease: 65.6 vs 98.5mL/min/1.73m(2)). Larger proportions in the groups aged ≥50 exhibited cardiac and/or cerebrovascular manifestations compared with patients aged 18-49years. The smaller proportion of patients receiving ERT aged ≥75years compared with the younger groups might reflect relatively milder disease burden or physician/patient reluctance to initiate/continue ERT at this age. Further studies are needed to increase knowledge of Fabry disease and ERT in later life.

  20. Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry

    PubMed Central

    Ortiz, Alberto; Abiose, Ademola; Bichet, Daniel G; Cabrera, Gustavo; Charrow, Joel; Germain, Dominique P; Hopkin, Robert J; Jovanovic, Ana; Linhart, Aleš; Maruti, Sonia S; Mauer, Michael; Oliveira, João P; Patel, Manesh R; Politei, Juan; Waldek, Stephen; Wanner, Christoph; Yoo, Han-Wook; Warnock, David G

    2016-01-01

    Background Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a ‘lag time’ to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. Methods The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years. Results The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40–58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated. Conclusions Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks. Trial registration number NCT00196742. PMID:26993266

  1. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    PubMed

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P < 0.01), anxiety (P = 0.05), depression and anxiety (P = 0.03), antisocial personality (P < 0.001), attention-deficit/hyperactivity (AD/H; P < 0.01), hyperactivity-impulsivity (P < 0.01), and aggressive behavior (P = 0.03) were associated with poorer adaptive functioning. Decreased social-adaptive functioning in this study was not statistically significantly associated to disease severity, pain, or level of vitality. This study shows for the first time that FD patients, particularly women, are affected by decreased social-adaptive functioning. Comprehensive treatment plans for FD should consider assessments and interventions to evaluate and improve social, occupational, and psychological functioning. Attention to the behavioral aspects of FD could lead to improved treatment outcome and improved quality of life. Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety

  2. Cognitive and psychological functioning in Fabry disease.

    PubMed

    Sigmundsdottir, Linda; Tchan, Michel C; Knopman, Alex A; Menzies, Graham C; Batchelor, Jennifer; Sillence, David O

    2014-11-01

    Fabry disease is an X-linked lysosomal storage disorder which can result in renal, cardiac, and cerebrovascular disease. Patients are at increased risk of stroke and neuroimaging studies note cerebrovascular pathology. This study provides a cognitive profile of a cohort of individuals with Fabry disease and investigates the impact of pain, age, renal, cardiac, and cerebrovascular functioning on cognition and psychological functioning. Seventeen Fabry patients (12 males) with ages ranging 25 to 60 years (M = 46.6+11.8), and 15 age-matched healthy controls (M = 46.2+12.7) were administered a comprehensive neuropsychological battery. Fabry males demonstrated slower speed of information processing, reduced performance on measures of executive functions (verbal generation, reasoning, problem solving, perseveration), were more likely to show clinically significant reductions, and were more likely to report symptoms of anxiety and depression. Conversely, Fabry females performed at a similar level to controls. Correlational analyses indicated a link between cognitive and clinical measures of disease severity.

  3. Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients.

    PubMed

    Young-Gqamana, Brandy; Brignol, Nastry; Chang, Hui-Hwa; Khanna, Richie; Soska, Rebecca; Fuller, Maria; Sitaraman, Sheela A; Germain, Dominique P; Giugliani, Roberto; Hughes, Derralynn A; Mehta, Atul; Nicholls, Kathy; Boudes, Pol; Lockhart, David J; Valenzano, Kenneth J; Benjamin, Elfrida R

    2013-01-01

    Fabry disease (FD) results from mutations in the gene (GLA) that encodes the lysosomal enzyme α-galactosidase A (α-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb3). Migalastat hydrochloride (GR181413A) is a pharmacological chaperone that selectively binds, stabilizes, and increases cellular levels of α-Gal A. Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. A liquid chromatography-tandem mass spectrometry method was developed to measure lyso-Gb3 in mouse tissues and human plasma. Oral administration of migalastat HCl to transgenic mice reduced elevated lyso-Gb3 levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively, generally equal to or greater than observed for GL-3. Furthermore, baseline plasma lyso-Gb3 levels were markedly elevated in six male FD patients enrolled in Phase 2 studies. Oral administration of migalastat HCl (150 mg QOD) reduced urine GL-3 and plasma lyso-Gb3 in three subjects (range: 15% to 46% within 48 weeks of treatment). In contrast, three showed no reductions in either substrate. These results suggest that measurement of tissue and/or plasma lyso-Gb3 is feasible and may be warranted in future studies of migalastat HCl or other new potential therapies for FD.

  4. Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study

    PubMed Central

    2013-01-01

    Background Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP). Methods In this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function. Results All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients. Conclusion Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction. PMID:23705943

  5. DNA damage in Fabry patients: An investigation of oxidative damage and repair.

    PubMed

    Biancini, Giovana Brondani; Moura, Dinara Jaqueline; Manini, Paula Regina; Faverzani, Jéssica Lamberty; Netto, Cristina Brinckmann Oliveira; Deon, Marion; Giugliani, Roberto; Saffi, Jenifer; Vargas, Carmen Regla

    2015-06-01

    Fabry disease (FD) is a lysosomal storage disorder associated with loss of activity of the enzyme α-galactosidase A. In addition to accumulation of α-galactosidase A substrates, other mechanisms may be involved in FD pathophysiology, such as inflammation and oxidative stress. Higher levels of oxidative damage to proteins and lipids in Fabry patients were previously reported. However, DNA damage by oxidative species in FD has not yet been studied. We investigated basal DNA damage, oxidative DNA damage, DNA repair capacity, and reactive species generation in Fabry patients and controls. To measure oxidative damage to purines and pyrimidines, the alkaline version of the comet assay was used with two endonucleases, formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). To evaluate DNA repair, a challenge assay with hydrogen peroxide was performed. Patients presented significantly higher levels of basal DNA damage and oxidative damage to purines. Oxidative DNA damage was induced in both DNA bases by H2O2 in patients. Fabry patients presented efficient DNA repair in both assays (with and without endonucleases) as well as significantly higher levels of oxidative species (measured by dichlorofluorescein content). Even if DNA repair be induced in Fabry patients (as a consequence of continuous exposure to oxidative species), the repair is not sufficient to reduce DNA damage to control levels.

  6. Nailfold capillaroscopy: Specific features in Fabry disease.

    PubMed

    Wasik, Jan S; Simon, Roger W; Meier, Thomas; Steinmann, Beat; Amann-Vesti, Beatrice R

    2009-01-01

    Fabry disease is a rare X-linked disorder caused by deficiency of alpha-galactosidase A. The metabolic defect results in the progressive accumulation of globotriaosylceramide within vascular cells leading to renal, cardiac and cerebrovascular manifestations. The aim of this study was to evaluate nailfold capillaroscopy as a non-invasive diagnostic tool in Fabry disease and to characterize morphological and functional changes of the capillaries in vivo. Twenty-five consecutive patients with Fabry disease (17 males) without enzyme-replacement therapy had been studied by fluorescence nailfold capillaroscopy. Macrocirculation of digital arteries was tested by digital pulse volume recording and patients had been asked about the presence of Raynaud phenomenon. Significant more bushy capillaries and clusters were present in Fabry patients (72%) compared to healthy controls (10%). No avascular fields had been seen, and in only one patient atypical architecture and in another one a giant capillary was present. Enhanced natrium-fluorescein diffusion into the pericapillary area has been observed in three male patients. Six patients (one female) reported Raynaud phenomenon of all fingers. In Fabry disease morphological and functional microangiopathy of nailfold capillaries is present. Furthermore, these new findings might explain, at least in part, the unusual high frequency of Raynaud phenomenon in Fabry patients, which has not been described so far. Our data suggest that capillaroscopy might be used as an additional non-invasive diagnostic tool for Fabry disease.

  7. Results of a nationwide screening for Anderson-Fabry disease among dialysis patients.

    PubMed

    Kotanko, Peter; Kramar, Reinhard; Devrnja, Danijela; Paschke, Eduard; Voigtländer, Till; Auinger, Martin; Pagliardini, Severo; Spada, Marco; Demmelbauer, Klaus; Lorenz, Matthias; Hauser, Anna-Christine; Kofler, Hans-Jörg; Lhotta, Karl; Neyer, Ulrich; Pronai, Wolfgang; Wallner, Manfred; Wieser, Clemens; Wiesholzer, Martin; Zodl, Herbert; Födinger, Manuela; Sunder-Plassmann, Gere

    2004-05-01

    Anderson-Fabry disease is possibly underdiagnosed in patients with end-stage renal disease. Nationwide screening was therefore undertaken for Anderson-Fabry disease among dialysis patients in Austria. Screening for alpha-galactosidase A (AGAL) deficiency was performed by a blood spot test. In patients with a positive screening test, AGAL activity in leukocytes was determined. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene. Fifty (90.9%) of 55 Austrian hemodialysis centers participated in this study; 2480 dialysis patients (80.1% of the Austrian dialysis population) were screened. In 85 patients, the screening test was positive (85 of 2480, 3.42%; women, 3.32%; men, 3.50%). Among these 85 patients, 4 men (in 3 of whom Anderson-Fabry disease was already known before screening) had a severely decreased and 11 subjects had a borderline low AGAL activity. Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. A nationwide screening of dialysis patients permitted detection of a hitherto unknown man with Anderson-Fabry disease. The overall prevalence among dialysis patients was at least ten times higher as compared with recent registry data. Screening programs among patients with end-stage renal disease, especially men, should be put in place to identify families with Anderson-Fabry disease who probably may benefit from specific clinical care, and perhaps from enzyme replacement therapy. In dialysis patients, however, there is no evidence to support enzyme replacement therapy at present.

  8. Fabry disease.

    PubMed

    Schiffmann, Raphael

    2015-01-01

    Fabry disease, an X-linked disorder of glycosphingolipids that is caused by mutations of the GLA gene that codes for α-galactosidase A, leads to dysfunction of many cell types and includes a systemic vasculopathy. As a result, patients have a markedly increased risk of developing ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction and chronic kidney disease. Virtually all complications of Fabry disease are non-specific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Recent studies suggested a much higher incidence of mutations of the GLA gene, suggesting that this disorder is under-diagnosed. However, some of the gene variants may be benign. Although the etiology of Fabry disease has been known for many years, the mechanism by which the accumulating α-D-galactosyl moieties cause this multi organ disorder has only recently been studied and is yet to be completely elucidated. Specific therapy for Fabry disease has been developed in the last few years but its role in the management of the disorder is still being investigated. Fortunately, standard 'non-specific' medical and surgical therapy is effective in slowing deterioration or compensating for organ failure in patients with Fabry disease.

  9. Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A)

    PubMed Central

    Lin, Hsiang-Yu; Liu, Hao-Chuan; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Hsu, Ting-Rong; Shen, Chia-I; Li, Shao-Tzu; Li, Cheng-Fang; Lee, Li-Hong; Lee, Pi-Chang; Huang, Chun-Kai; Chiang, Chuan-Chi; Lin, Ching-Yuang; Lin, Shuan-Pei; Niu, Dau-Ming

    2013-01-01

    Objective Current studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A). Design Retrospective cohort study. Setting Tertiary medical centre. Participants 21 patients with cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with classic Fabry disease (4 men and 11 women) treated with biweekly intravenous infusions of agalsidase β (1 mg/kg) or agalsidase α (0.2 mg/kg) for at least 6 months. Outcome measures These data were collected at the time before enzyme replacement therapy (ERT) began and followed up after ERT for at least 6 months, including patient demographics, medical history, parameter changes of cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3) and Mainz Severity Score Index. Results After 6–39 months of ERT, plasma lyso-Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with cardiac-type and classic Fabry disease, respectively, which indicated an improvement of disease severity. For patients with cardiac-type Fabry disease, echocardiography revealed the reduction or stabilisation of left ventricular mass index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively, as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type. Most patients showed stable renal function after ERT. There were statistically significant improvements (p<0.05) between the data at baseline and those after ERT for values of plasma lyso-Gb3, LVMI, IVS, LPW and Mainz Severity Score Index. No severe clinical events were reported during the treatment. Conclusions ERT is beneficial and appears to be safe for Taiwanese patients with cardiac-type Fabry disease, as well as for those with the classic type. PMID:23864212

  10. Endomyocardial biopsies in patients with left ventricular hypertrophy and a common Chinese later-onset fabry mutation (IVS4 + 919G > A)

    PubMed Central

    2014-01-01

    Background In Taiwan, DNA-based newborn screening showed a surprisingly high incidence of a cardiac Fabry mutation (IVS4 + 919G > A). The prevalence of this mutation is too high to be believed that it is a real pathogenic mutation. The purpose of this study is to identify the cardiac pathologic characteristics in patients with left ventricular hypertrophy and this mutation Methods and results Endomyocardial biopsies were obtained in 22 patients (Median age: 61, males: 17; females: 5) with left ventricular hypertrophy and the IVS4 + 919G > A mutation; five patients had not received enzyme replacement therapy (ERT) before biopsy, while the other 17 patients had received ERT from 8 months to 51 months. Except for three patients who had received ERT for more than 3 years, all other patients showed significant pathological change and globotriaosylceramide (Gb3) accumulation in their cardiomyocytes. In contrast to classical Fabry patients, no Gb3 accumulation was found in the capillary endothelial cells of any of our patients. Fourteen patients (63.6%) were found to have myofibrillolysis. Conclusions All of the untreated and most of the treated IVS4 + 919G > A patients showed typical pathological changes of Fabry disease in their cardiomyocytes. No endothelial accumulation of Gb3 was found, which is similar to the findings of several previous reports regarding later-onset Fabry disease. This result highly suggests that the IVS4 + 919G > A is a real pathogenic later-onset Fabry mutation. PMID:24980630

  11. Switch from agalsidase beta to agalsidase alfa in the enzyme replacement therapy of patients with Fabry disease in Latin America.

    PubMed

    Ripeau, Diego; Amartino, Hernán; Cedrolla, Martín; Urtiaga, Luis; Urdaneta, Bella; Cano, Marilis; Valdez, Rita; Antongiovanni, Norberto; Masllorens, Francisca

    2017-01-01

    There are currently two available enzyme replacement therapies for Fabry disease and little information regarding efficacy and safety of switching therapies. Between 2009 and 2012 there was a worldwide shortage of agalsidase beta and patients on that enzyme were switched to agalsidase alfa. This retrospective observational study assessed a 2-year period of efficacy and safety in a population of Fabry patients, in Argentina (30 patients) and Venezuela (3 patients), who switched therapies from algasidase beta to agalsidase alfa. Thirty-three patients completed 24-months follow-up after the switch (age 32.4 ± 2.0, range 10.0-55.9 years; male: female 23:10). Measures of renal function such as estimated glomerular filtration rate remained almost unchanged in 31 patients without end stage renal disease over the 2 years after switching and urine protein excretion continued stable. Cardiac functional parameters: left ventricular mass index, interventricular septum, left ventricular posterior wall showed no significant change from baseline in the 33 patients. Quality of life, pain and disease severity scores were mostly unchanged after 24-months and agalsidase alfa was generally well tolerated. Our findings showed there is no significant change in the efficacy measured through the renal or cardiac function, quality of life, pain, disease severity scoring and safety for at least 2 years after switching from agalsidase beta to agalsidase alfa.

  12. Screening for Fabry's disease in young patients with ischemic stroke in a Chinese population.

    PubMed

    Song, Xiaowei; Xue, Sufang; Zhao, Jingyan; Wu, Jian

    2017-04-01

    Fabry disease is an X-linked lysosomal storage disorder frequently associated with cerebrovascular disease. Data regarding Fabry disease and ischemic stroke has been lacking in China. In this study, we investigated the prevalence of Fabry disease and the distribution of the alpha-galactosidase A (α-GalA) gene - GLA mutations in young stroke patients in the Chinese population and its association with stroke subtypes. A total of 357 ischemic stroke patients admitted to Xuanwu Hospital of Capital Medical University, aged 18-55 years old, including 293 patients with cerebral infarction and 64 patients with transient ischemic attack, were enrolled in this study. Mutations in the GLA gene were screened by Sanger sequencing. Enzyme levels were measured to further confirm the disease in patients with the gene mutation. The mutation frequency was compared among different stroke subtypes and further compared with the control group individually. No pathogenic mutations in the coding regions of the GLA gene were identified in this group of patients and thus no Fabry disease was found in our study. However, the frequency of an intronic polymorphism c.-10C>T was significantly different among different Trial of Org 10172 in Acute Stroke Treatment subtypes (p < 0.01). The frequency of the c.-10C>T polymorphism in patients with stroke due to other causes and undetermined causes was much higher than that in the control group (OR = 3.18, 95% CI: 1.29-7.83, p < 0.01). Fabry disease is a rare disease, and it will not benefit to screen all stroke patients. In addition, our results suggested that the c.-10C>T polymorphism may be a risk factor for ischemic stroke of other and undetermined causes. Further study is required to confirm our findings.

  13. Inner ear function in children with Fabry disease.

    PubMed

    Keilmann, A

    2003-12-01

    The prevalence of hearing loss in patients with Fabry disease is still uncertain. This paper examines hearing loss in a group of young patients with Fabry disease. A clinical ear nose and throat examination, pure-tone air and bone conduction audiometry, speech audiometry and middle ear testing (tympanometry and acoustic reflex testing) were carried out in four girls and two boys with Fabry disease (age, 7-17 years), receiving enzyme replacement therapy (ERT). None of the patients complained of a hearing disorder or suffered from hearing loss. Three female patients reported tinnitus; however, this was not reported as being a problem. One boy reported tinnitus for the first time during 6 months of ERT. Based on this small sample of patients, it appears that the hearing disorders associated with Fabry disease develop mainly in adulthood. Tinnitus may be an earlier symptom than previously thought in Fabry disease.

  14. Increased oxidative stress contributes to cardiomyocyte dysfunction and death in patients with Fabry disease cardiomyopathy.

    PubMed

    Chimenti, Cristina; Scopelliti, Fernanda; Vulpis, Elisabetta; Tafani, Marco; Villanova, Lidia; Verardo, Romina; De Paulis, Ruggero; Russo, Matteo A; Frustaci, Andrea

    2015-11-01

    Cardiac dysfunction of Fabry disease (FD) has been associated with myofilament damage and cell death as result of α-galactosidase A deficiency and globotriaosylceramide accumulation. We sought to evaluate the role of oxidative stress in FD cardiomyocyte dysfunction. Myocardial tissue from 18 patients with FD was investigated for the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine by immunohistochemistry. Western blot analysis for nitrotyrosine was also performed. Oxidative damage to DNA was investigated by immunostaining for 8-hydroxydeoxyguanosine (8-OHdG), whereas apoptosis was evaluated by in situ ligation with hairpin probes. iNOS and nitrotyrosine expression was increased in FD hearts compared with hypertrophic cardiomyopathy and normal controls. Remarkably, immunostaining was homogeneously expressed in FD male cardiomyocytes, whereas it was only detected in the affected cardiomyocytes of FD females. Western blot analysis confirmed an increase in FD cardiomyocyte protein nitration compared with controls. 8-OHdG was expressed in 25% of cardiomyocyte nuclei from FD patients, whereas it was absent in controls. The intensity of immunostaining for iNOS/nitrotyrosine correlated with 8-OHdG expression in cardiomyocyte nuclei. Apoptosis of FD cardiomyocytes was 187-fold higher than in controls, and apoptotic nuclei were positive for 8-OHdG. Cardiac dysfunction of FD reflects increased myocardial nitric oxide production with oxidative damage of cardiomyocyte myofilaments and DNA, causing cell dysfunction and death.

  15. Fabry disease.

    PubMed

    Toyooka, Keiko

    2013-01-01

    Fabry disease results from deficient activity of the enzyme α-galactosidase A and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. The main neurological presentations of Fabry disease patients are painful neuropathy, hypohidrosis, and stroke. Fabry neuropathy is characterized as a length-dependent peripheral neuropathy affecting mainly the small myelinated (Aδ) fibers and unmyelinated (C) fibers. Enzyme replacement therapy (ERT) has been shown to have some positive effects on the reduction of neuropathic pain, the improvement of detection threshold for thermal sensation, and sweat function. On the contrary, the effect of ERT on the central nervous system has not been established. Early initiation of ERT before irreversible organ failure is extremely important, and alternative therapeutic approaches are currently being explored. Heterozygotes suffer from peripheral neuropathy at a higher rate than previously shown, significant multisystemic disease, and severely decreased quality of life. As well as being carriers, heterozygotes also display symptoms of Fabry disease, and should be carefully monitored and given adequate therapy.

  16. Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch.

    PubMed

    Weidemann, Frank; Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; Guerrero González, Hans; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

    2014-04-01

    Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3-0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m(2) (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0-606) mg/g to 216 (0-2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.

  17. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease

    PubMed Central

    Germain, Dominique P; Charrow, Joel; Desnick, Robert J; Guffon, Nathalie; Kempf, Judy; Lachmann, Robin H; Lemay, Roberta; Linthorst, Gabor E; Packman, Seymour; Scott, C Ronald; Waldek, Stephen; Warnock, David G; Weinreb, Neal J; Wilcox, William R

    2015-01-01

    Background Fabry disease results from deficient α-galactosidase A activity and globotriaosylceramide accumulation causing renal insufficiency, strokes, hypertrophic cardiomyopathy and early demise. We assessed the 10-year outcome of recombinant α-galactosidase A therapy. Methods The outcomes (severe clinical events, renal function, cardiac structure) of 52/58 patients with classic Fabry disease from the phase 3 clinical trial and extension study, and the Fabry Registry were evaluated. Disease progression rates for patients with low renal involvement (LRI, n=32) or high renal involvement (HRI, n=20) at baseline were assessed. Results 81% of patients (42/52) did not experience any severe clinical event during the treatment interval and 94% (49/52) were alive at the end of the study period. Ten patients reported a total of 16 events. Patients classified as LRI started therapy 13 years younger than HRI (mean 25 years vs 38 years). Mean slopes for estimated glomerular filtration rate for LRI and HRI were −1.89 mL/min/1.73 m2/year and −6.82 mL/min/1.73 m2/year, respectively. Overall, the mean left ventricular posterior wall thickness and interventricular septum thickness remained unchanged and normal. Patients who initiated treatment at age ≥40 years exhibited significant increase in left ventricular posterior wall thickness and interventricular septum thickness. Mean plasma globotriaosylceramide normalised within 6 months. Conclusions This 10-year study documents the effectiveness of agalsidase beta (1 mg/kg/2 weeks) in patients with Fabry disease. Most patients remained alive and event-free. Patients who initiated treatment at a younger age and with less kidney involvement benefited the most from therapy. Patients who initiated treatment at older ages and/or had advanced renal disease experienced disease progression. PMID:25795794

  18. [Fabry disease].

    PubMed

    Stephan, F; Haber, R

    2017-02-01

    Fabry disease, also known as Anderson-Fabry disease or angiokeratoma corporis diffusum universale, is an X-linked recessive form of sphingolipidosis caused by total or partial deficiency of the lysosomal hydrolase, alpha-galactosidase A. From the youngest age, it results in a gradual ubiquitous build-up of glycosphingolipids that are not degraded by the missing enzyme. Cutaneous, neurological, nephrologic, cardiac, gastrointestinal, ophthalmological, respiratory, cochleovestibular and haematological involvement are responsible for increased mortality and significant impairment of quality of life in subjects affected by the disease. Angiokeratomas are the most common cutaneous sign of this disease, although they are not specific to it and must be distinguished from angiokeratomas either occurring in isolation or associated with systemic diseases. Other cutaneous signs encountered in this disease include hyperhidrosis, oral lesions, lower limb oedemas, etc. The diagnosis is mainly clinical and should be considered in the presence of a personal and/or familial history; it is confirmed by assay of enzyme activity within leucocytes or by molecular studies. Management is multidisciplinary and involves symptomatic treatment as well as specific treatment, resulting in improved survival and enhanced quality of life for patients presenting the disease. Enzyme replacement therapy with alpha-galactosidase A forms the cornerstone of specific treatment and may be associated with other types of treatments such as galactose and molecular chaperones. Gene therapy is now also used extensively. At present, these marked therapeutic advances, which closely involve dermatologists, could help transform the prognosis for patients presenting Fabry disease.

  19. Fabry disease in children: a federal screening programme in Russia.

    PubMed

    Namazova-Baranova, Leyla Seymurovna; Baranov, Alexander Alexandrovich; Pushkov, Aleksander Alekseevich; Savostyanov, Kirill Victorovich

    2017-09-04

    Our objective was to examine the prevalence of Fabry disease in Russian children with chronic pain in the distal limbs. This non-interventional, multi-centre study included children 2-18 years of age with chronic recurrent unilateral or bilateral pain, burning, or acroparesthesia in the hands or feet. The presence of Fabry disease was defined by abnormal alpha-galactosidase A activity in males or alpha-galactosidase gene (GLA) mutation in females. Among 214 patients (110 males), 84.1% had bilateral limb pain and 31.8% had unilateral limb pain recorded at some time point; 61 (28.5%) patients had a positive family history possibly associated with Fabry disease. Alpha-galactosidase A activity was within the normal range in all 109 of the male patients tested. One female patient had a GLA mutation (C937G > T) and alpha-galactosidase A activity within the normal range. We did not find definitive evidence of Fabry disease in these children with a history of chronic recurrent unilateral or bilateral limb pain or acroparesthesia. The presence of chronic limb pain does not appear to be highly predictive of a diagnosis of Fabry disease in Russian children and adolescents, suggesting that key early signs and symptoms of Fabry disease are not specific to the disease. What is Known: • Signs and symptoms of Fabry disease are seen in children < 10 years of age; pain in the distal limbs is a common early symptom. What is New: • Fabry disease was not diagnosed in this population of Russian children with a history of chronic limb pain. • The presence of acroparesthesia or chronic limb pain does not appear to be highly predictive of a diagnosis of Fabry disease in Russian children and adolescents, suggesting that these early symptoms of Fabry disease are not specific to the disease.

  20. Identification of a Novel GLA Mutation (L206 P) in a Patient with Fabry Disease.

    PubMed

    Kim, Ji-Hoon; Kim, Gee-Hee; Park, Hoon-Suk; Choi, Jin-A; Bae, Jung-Min; Cho, Uiju

    2017-03-01

    We report a new α-Galactosidase A (αGal-A) mutation in a 39-year-old Korean born, male Fabry disease patient. Fabry disease is a devastating, progressive inborn error of metabolism caused by X-linked genetic mutations. In this case, the first clinical symptom to occur was in childhood consisting of a burning pain originating in the extremities then radiating inwards to the limbs. This patient also stated to have ringing in his ears, angiokeratomas on his trunk, and cornea verticillata. He visited an outpatient cardiologist due to intermittent and atypical chest discomfort at the age of 39. Electrocardiographic and echocardiographic examination showed left ventricular hypertrophy. A physical examination revealed proteinuria without hematuria. The patient's plasma αGal-A activity was markedly lower than the mean value of the controls. After genetic counseling and obtaining written informed consent, we identified one hemizygous mutation in exon 4 of galactosidase alpha, c.617T>C (p.Leu206 Pro). He was eventually diagnosed as having Fabry disease.

  1. Identification of a Novel GLA Mutation (L206 P) in a Patient with Fabry Disease

    PubMed Central

    Kim, Ji-Hoon; Park, Hoon-Suk; Choi, Jin-A; Bae, Jung-Min; Cho, Uiju

    2017-01-01

    We report a new α-Galactosidase A (αGal-A) mutation in a 39-year-old Korean born, male Fabry disease patient. Fabry disease is a devastating, progressive inborn error of metabolism caused by X-linked genetic mutations. In this case, the first clinical symptom to occur was in childhood consisting of a burning pain originating in the extremities then radiating inwards to the limbs. This patient also stated to have ringing in his ears, angiokeratomas on his trunk, and cornea verticillata. He visited an outpatient cardiologist due to intermittent and atypical chest discomfort at the age of 39. Electrocardiographic and echocardiographic examination showed left ventricular hypertrophy. A physical examination revealed proteinuria without hematuria. The patient's plasma αGal-A activity was markedly lower than the mean value of the controls. After genetic counseling and obtaining written informed consent, we identified one hemizygous mutation in exon 4 of galactosidase alpha, c.617T>C (p.Leu206 Pro). He was eventually diagnosed as having Fabry disease. PMID:28382085

  2. Fabry disease: a review of current management strategies.

    PubMed

    Mehta, A; Beck, M; Eyskens, F; Feliciani, C; Kantola, I; Ramaswami, U; Rolfs, A; Rivera, A; Waldek, S; Germain, D P

    2010-09-01

    Fabry disease is an X-linked inherited condition due to the absence or reduction of alpha-galactosidase activity in lysosomes, that results in accumulation of globotriaosylceramide (Gb3) and related neutral glycosphingolipids. Manifestations of Fabry disease include serious and progressive impairment of renal and cardiac function. In addition, patients experience pain, gastrointestinal disturbance, transient ischaemic attacks and strokes. Additional effects on the skin, eyes, ears, lungs and bones are often seen. The first symptoms of classic Fabry disease usually appear in childhood. Despite being X-linked, females can suffer the same severity of symptoms as males, and life expectancy is reduced in both females and males. Enzyme replacement therapy (ERT) can stabilize the progression of the disease. The rarity of the classic form of Fabry disease, however, means that there is a need to improve the knowledge and understanding that the majority of physicians have concerning Fabry disease, in order to avoid misdiagnosis and/or delayed diagnosis. This review aims to raise awareness of the signs and symptoms of Fabry disease; to provide a general diagnostic algorithm and to give an overview of the effects of ERT and concomitant treatments. We highlight a need to develop comprehensive international guidelines to optimize ERT and adjunctive therapy in patients with Fabry disease, including females and children.

  3. Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients.

    PubMed

    Gonçalves, Maria J; Mourão, Ana F; Martinho, António; Simões, Olívia; Melo-Gomes, José; Salgado, Manuel; Estanqueiro, Paula; Ribeiro, Célia; Brito, Iva; Fonseca, João E; Canhão, Helena

    2017-01-01

    Fabry's disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No "classic" pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292).

  4. Fabry disease

    PubMed Central

    2010-01-01

    Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs

  5. Age at First Cardiac Symptoms in Fabry Disease: Association with a Chinese Hotspot Fabry Mutation (IVS4+919G>A), Classical Fabry Mutations, and Sex in a Taiwanese Population from the Fabry Outcome Survey (FOS).

    PubMed

    Liu, Hao-Chuan; Perrin, Amandine; Hsu, Ting-Rong; Yang, Chia-Feng; Lin, Hsiang-Yu; Yu, Wen-Chung; Niu, Dau-Ming

    2015-01-01

    This is a descriptive analysis of a cohort of 59 Taiwanese patients with Fabry disease and either classical Fabry or cardiac variant IVS4+919G>A (IVS4) mutations from a disease registry, the Fabry Outcome Survey (FOS; sponsored by Shire). Most of our classical Fabry patients were symptomatic and were identified upon seeking medical advice at our clinics, whereas most of our IVS4 patients attended our clinics after newborn screening identified this mutation in their grandsons. The objective was to determine differences in cardiac manifestations between patients with classical Fabry or IVS4 mutations by comparing age at onset of selected cardiac symptoms. Data were extracted in August 2013 and analyzed retrospectively. Fifty-nine Taiwanese patients (median age at extract 60.7 years [range 15.0-86.9]; n = 36 [61%] male) with proven IVS4 (n = 41 [69%]) or classical Fabry mutations (n = 18 [31%]) had available data on cardiac symptoms. Of 55 (93%) patients with reported left ventricular hypertrophy (LVH), mean [SD] age (years) at first symptom was lower in classical Fabry males (30.0 [15.1]; n = 4) than classical Fabry females (49.6 [8.9]; n = 11; p < 0.05), but not in IVS4 females (57.4 [13.7]; n = 10) compared with IVS4 males (55.9 [11.3]; n = 30). Mean age at first LVH diagnosis was significantly lower in classical Fabry males versus IVS4 males (p < 0.05). No significant difference in age at onset of arrhythmia or conductive abnormality, chest pain, or palpitations or cardiac syncope was found between the groups. The most noteworthy finding of this study is the lack of a significant gender sex difference in age at onset of cardiac symptoms in IVS4 patients.

  6. Electroneuromyographic Features in Fabry Disease: A Retrospective Review

    PubMed Central

    AKPINAR, Çetin Kürşad; TÜRKER, Hande; BAYRAK, Oytun; CENGİZ, Nilgün

    2015-01-01

    Introduction Fabry disease (FD) is an X-linked recessive inherited disorder characterized by lysosomal alpha-galactosidase deficiency. The purpose of our study was to assess and compare the electroneuromyographic (ENMG) findings of 15 patients with Fabry disease and the electroneurographic (ENG) findings of 15 healthy controls. We have not encountered any similar study in the medical literature of our country. Therefore, we believe that our study will contribute to national literature. Methods Fifteen patients with Fabry disease, 13 females and 2 males and 15 healthy controls, 13 females and 2 males, were included in the study. The definite diagnosis of patients with Fabry disease was made based on the enzyme level and genetic mutation. The patients with Fabry disease were examined with ENMG, while the healthy control group was examined with ENG. In the patients with a normal ENMG examination, neuropathic pain was attributed to the small fiber involvement. Results Patients with Fabry disease had neuropathic pain (LANSS score≥12). While neurological examination was normal in eight patients, glove- and stocking-type hypoesthesia and decreased deep tendon reflexes were observed in five and two patients, respectively. Axonal polyneuropathy was detected in one patient. The ENMG examinations of the other patients were normal. Enzyme replacement therapy could not be initiated in one patient because of pregnancy. The neurological examination of the healthy control group was normal. There was no statistically significant difference between the ENMG features of both groups (p>.05). As in other studies, a routine ENMG examination was normal in our patients with early-stage Fabry disease. Neuropathic pain, seen in patients with Fabry disease in literature, is thought to be due to small fiber involvement. Conclusion Fabry disease should be considered in the differential diagnosis of patients with neuropathic pain at young ages. It should be kept in mind that ENMG examination

  7. Pedigree analysis of Mexican families with Fabry disease as a powerful tool for identification of heterozygous females.

    PubMed

    Gutiérrez-Amavizca, B E; Orozco-Castellanos, R; R Padilla-Gutiérrez, J; Valle, Y; Figuera, L E

    2014-08-28

    Fabry disease (FD) is an X-linked lysosomal storage disease caused by α-galactosidase A deficiency; in contrast to other X-linked diseases, heterozygous females can be as affected as men. The construction and analysis of a family pedigree is a powerful tool to aid clinicians in diagnosis, establishment of inheritance pattern, and early detection of potentially affected relatives. The present study highlights the importance of pedigree analysis in families with FD for identifying other possibly affected relatives and investigating the clinical manifestations. This clinical report included 12 Mexican index cases with confirmed FD diagnosis. We constructed and analyzed their pedigree, and diagnosed FD in 24 affected relatives. Clinical features were similar to those reported for other populations. Pedigree analysis further identified an additional 30 women as possible carriers. We conclude that pedigree construction and analysis is a useful tool to help physicians detect and diagnose relatives at risk for FD, particularly heterozygous females, so that they can receive genetic counseling and early treatment. Mexican families with FD were similar to other populations reported in the literature, and our findings confirmed that heterozygous females can have signs and symptoms ranging from subtle manifestations to the classical severe presentation described in males.

  8. Interleukin-18 deteriorates Fabry cardiomyopathy and contributes to the development of left ventricular hypertrophy in Fabry patients with GLA IVS4+919 G>A mutation.

    PubMed

    Chien, Yueh; Chien, Chian-Shiu; Chiang, Huai-Chih; Huang, Wei-Lin; Chou, Shih-Jie; Chang, Wei-Chao; Chang, Yuh-Lih; Leu, Hsin-Bang; Chen, Kuan-Hsuan; Wang, Kang-Ling; Lai, Ying-Hsiu; Liu, Yung-Yang; Lu, Kai-Hsi; Li, Hsin-Yang; Sung, Yen-Jen; Jong, Yuh-Jyh; Chen, Yann-Jang; Chen, Chung-Hsuan; Yu, Wen-Chung

    2016-12-27

    A high incidence of GLA IVS4+919 G>A mutation in patients with Fabry disease of the later-onset cardiac phenotype, has been reported in Taiwan. However, suitable biomarkers or potential therapeutic surrogates for Fabry cardiomyopathy (FC) in such patients under enzyme replacement treatment (ERT) remain unknown. Using FC patients carrying IVS4+919 G>A mutation, we constructed an induced pluripotent stem cell (iPSC)-based disease model to investigate the pathogenetic biomarkers and potential therapeutic targets in ERT-treated FC. The iPSC-differentiated cardiomyocytes derived from FC-patients (FC-iPSC-CMs) carried IVS4+919 G>A mutation recapitulating FC characteristics, including low α-galactosidase A enzyme activity, cellular hypertrophy, and massive globotriaosylceramide accumulation. Microarray analysis revealed that interleukin-18 (IL-18), a pleiotropic cytokine involved in various myocardial diseases, was the most highly upregulated marker in FC-iPSC-CMs. Meanwhile, IL-18 levels were found to be significantly elevated in the culture media of FC-iPSC-CMs and patients' sera. Notably, the serum IL-18 levels were highly paralleled with the progression of left ventricular hypertrophy in Fabry patients receiving ERT. Finally, using FC-iPSC-CMs as in vitro FC model, neutralization of IL-18 with specific antibodies combined with ERT synergistically reduced the secretion of IL-18 and the progression of cardiomyocyte hypertrophy in FC-iPSC-CMs. Our data demonstrated that cardiac IL-18 and circulating IL-18 are involved in the pathogenesis of FC and LVH. IL-18 may be a novel marker for evaluating ERT efficacy, and targeting IL-18 might be a potential adjunctive therapy combined with ERT for the treatment of advanced cardiomyopathy in FC patients with IVS4+919 G>A mutation.

  9. Interleukin-18 deteriorates Fabry cardiomyopathy and contributes to the development of left ventricular hypertrophy in Fabry patients with GLA IVS4+919 G>A mutation

    PubMed Central

    Huang, Wei-Lin; Chou, Shih-Jie; Chang, Wei-Chao; Chang, Yuh-Lih; Leu, Hsin-Bang; Chen, Kuan-Hsuan; Wang, Kang-Ling; Lai, Ying-Hsiu; Liu, Yung-Yang; Lu, Kai-Hsi; Li, Hsin-Yang; Sung, Yen-Jen; Jong, Yuh-Jyh; Chen, Yann-Jang; Chen, Chung-Hsuan; Yu, Wen-Chung

    2016-01-01

    Rationale A high incidence of GLA IVS4+919 G>A mutation in patients with Fabry disease of the later-onset cardiac phenotype, has been reported in Taiwan. However, suitable biomarkers or potential therapeutic surrogates for Fabry cardiomyopathy (FC) in such patients under enzyme replacement treatment (ERT) remain unknown. Objective Using FC patients carrying IVS4+919 G>A mutation, we constructed an induced pluripotent stem cell (iPSC)-based disease model to investigate the pathogenetic biomarkers and potential therapeutic targets in ERT-treated FC. Results and methods The iPSC-differentiated cardiomyocytes derived from FC-patients (FC-iPSC-CMs) carried IVS4+919 G>A mutation recapitulating FC characteristics, including low α-galactosidase A enzyme activity, cellular hypertrophy, and massive globotriaosylceramide accumulation. Microarray analysis revealed that interleukin-18 (IL-18), a pleiotropic cytokine involved in various myocardial diseases, was the most highly upregulated marker in FC-iPSC-CMs. Meanwhile, IL-18 levels were found to be significantly elevated in the culture media of FC-iPSC-CMs and patients’ sera. Notably, the serum IL-18 levels were highly paralleled with the progression of left ventricular hypertrophy in Fabry patients receiving ERT. Finally, using FC-iPSC-CMs as in vitro FC model, neutralization of IL-18 with specific antibodies combined with ERT synergistically reduced the secretion of IL-18 and the progression of cardiomyocyte hypertrophy in FC-iPSC-CMs. Conclusion Our data demonstrated that cardiac IL-18 and circulating IL-18 are involved in the pathogenesis of FC and LVH. IL-18 may be a novel marker for evaluating ERT efficacy, and targeting IL-18 might be a potential adjunctive therapy combined with ERT for the treatment of advanced cardiomyopathy in FC patients with IVS4+919 G>A mutation. PMID:27888626

  10. Fabry Disease

    MedlinePlus

    ... Page You are here Home » Disorders » All Disorders Fabry Disease Information Page Fabry Disease Information Page What research is being done? The ... treat and prevent lipid storage diseases such as Fabry disease. Researchers hope to identify biomarkers -- signs that may ...

  11. Anderson-Fabry disease: a multiorgan disease.

    PubMed

    Tuttolomondo, Antonino; Pecoraro, Rosaria; Simonetta, Irene; Miceli, Salvatore; Pinto, Antonio; Licata, Giuseppe

    2013-01-01

    Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A. FD causes glycolipids, such as globotriaosylceramide (Gb3), to accumulate in the vascular endothelium of several organs (Fig. 2), including the skin, kidneys, nervous system, and heart, thereby triggering inflammation and fibrosis. These processes generally result in organ dysfunction, which is usually the first clinical evidence of FD. Patients with classic FD have various symptoms, eg, acroparesthesias, hypohidrosis, angiokeratomas, corneal opacities, cerebrovascular lesions, cardiac disorders, andrenal dysfunction.However, evolving knowledge about the natural course of disease suggests that it is more appropriate to describe FD as a disease with a wide spectrum of heterogeneously progressive clinical phenotypes. Indeed, most female heterozygotes develop symptoms due to yet undetermined mechanisms and a high percentage of females develops vital organ involvement including the kidneys, heart and/or brain about a decade later than males. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. The principal clinical manifestations in Fabry disease consist of artery associated complications (such as cerebral disease and nephropathy), but the pathophysiology of this specific vasculopathy is unclear. Several studies

  12. [Fabry disease].

    PubMed

    Boggio, Paula; Luna, Paula Carolina; Abad, María Eugenia; Larralde, Margarita

    2009-01-01

    Fabry disease is an uncommon, X-linked lysosomal storage disorder, caused by partial or complete deficiency of the enzyme a-galactosidase A. The defect leads to accumulation of uncleaved globotriaosylceramide on the vascular endothelium and visceral tissues, being the skin, heart, kidneys and central nervous system the most affected organs. We performed review of the literature related to the disease and emphasized that early recognition of angiokeratomas and hypohidrosis are key diagnostic signs of this serious disease. We also addressed the need of multidisciplinary assessment of these patients.

  13. Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

    PubMed

    Politei, J; Schenone, A B; Cabrera, G; Heguilen, R; Szlago, M

    2016-01-01

    We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta.

  14. Fabry disease presenting as apical left ventricular hypertrophy in a patient carrying the missense mutation R118C.

    PubMed

    Caetano, Francisca; Botelho, Ana; Mota, Paula; Silva, Joana; Leitão Marques, António

    2014-03-01

    Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by abnormalities of the GLA gene, which encodes the enzyme α-galactosidase A. A deficiency of this enzyme leads to the lysosomal accumulation of glycosphingolipids, which may cause left ventricular hypertrophy that is typically concentric and symmetric. We present the case of a 60-year-old woman with symptoms of dyspnea, atypical chest pain and palpitations, in whom a transthoracic echocardiogram revealed an apical variant of hypertrophic cardiomyopathy. Analysis of specific sarcomeric genetic mutations was negative. The patient underwent a screening protocol for Anderson-Fabry disease, using a dried blood spot test, which was standard at our institution for patients with left ventricular hypertrophy. The enzymatic activity assay revealed reduced α-galactosidase A enzymatic activity. Molecular analysis identified a missense point mutation in the GLA gene (p.R118C). This case report shows that Anderson-Fabry disease may cause an apical form of left ventricular hypertrophy. The diagnosis was only achieved because of systematic screening, which highlights the importance of screening for Anderson-Fabry disease in patients with unexplained left ventricular hypertrophy, including those presenting with more unusual patterns, such as apical variants of left ventricular hypertrophy. This case also supports the idea that the missense mutation R118C is indeed a true pathogenic mutation of Anderson-Fabry disease.

  15. Cognitive and Psychological Functioning in Fabry Disease

    PubMed Central

    Sigmundsdottir, Linda; Tchan, Michel C.; Knopman, Alex A.; Menzies, Graham C.; Batchelor, Jennifer; Sillence, David O.

    2014-01-01

    Fabry disease is an X-linked lysosomal storage disorder which can result in renal, cardiac, and cerebrovascular disease. Patients are at increased risk of stroke and neuroimaging studies note cerebrovascular pathology. This study provides a cognitive profile of a cohort of individuals with Fabry disease and investigates the impact of pain, age, renal, cardiac, and cerebrovascular functioning on cognition and psychological functioning. Seventeen Fabry patients (12 males) with ages ranging 25 to 60 years (M = 46.6+11.8), and 15 age-matched healthy controls (M = 46.2+12.7) were administered a comprehensive neuropsychological battery. Fabry males demonstrated slower speed of information processing, reduced performance on measures of executive functions (verbal generation, reasoning, problem solving, perseveration), were more likely to show clinically significant reductions, and were more likely to report symptoms of anxiety and depression. Conversely, Fabry females performed at a similar level to controls. Correlational analyses indicated a link between cognitive and clinical measures of disease severity. PMID:25319043

  16. Novel α-galactosidase A mutation in patients with severe cardiac manifestations of Fabry disease.

    PubMed

    Duro, Giovanni; Musumeci, M Beatrice; Colomba, Paolo; Zizzo, Carmela; Albeggiani, Giuseppe; Mastromarino, Vittoria; Volpe, Massimo; Autore, Camillo

    2014-02-10

    Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of α-galactosidase A (α-gal A), a lysosomal hydrolase. This inactivation is responsible for the accumulation of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. Fabry is considered a rare disease, with an incidence of 1:40,000; however, there are good reasons to believe that it is often seen but rarely diagnosed. To date, more than 600 mutations have been identified in human GLA gene that are responsible for FD. We describe the case of a 54-year-old male patient, who presented with left ventricular hypertrophy, chronic renal failure and acroparaesthesias, which are considered to be specific features of FD. Clinical and instrumental investigations showed several cardiovascular manifestations. The molecular analysis of GLA gene revealed a novel mutation in the fifth exon, called N249K, and the enzymatic analysis showed no α-galactosidase A activity. Family screening detected the same mutation in some relatives and also the enzymatic analysis confirmed the diagnosis of FD. In conclusion, these data suggest that the N249K mutation may be associated with cardiac manifestations of FD combined with other classical features of the disease.

  17. Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN)

    PubMed Central

    Fogo, Agnes B.; Bostad, Leif; Svarstad, Einar; Cook, William J.; Moll, Solange; Barbey, Federic; Geldenhuys, Laurette; West, Michael; Ferluga, Dusan; Vujkovac, Bojan; Howie, Alexander J.; Burns, Áine; Reeve, Roy; Waldek, Stephen; Noël, Laure-Hélène; Grünfeld, Jean-Pierre; Valbuena, Carmen; Oliveira, João Paulo; Müller, Justus; Breunig, Frank; Zhang, Xiao; Warnock, David G.

    2010-01-01

    Background. In Fabry nephropathy, alpha-galactosidase deficiency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria and progressive loss of kidney function. Methods. An international working group of nephrologists from 11 Fabry centres identified adult Fabry patients, and pathologists scored histologic changes on renal biopsies. A standardized scoring system was developed with a modified Delphi technique assessing 59 Fabry nephropathy cases. Each case was scored independently of clinical information by at least three pathologists with an average final score reported. Results. We assessed 35 males (mean age 36.4 years) and 24 females (43.9 years) who mostly had clinically mild Fabry nephropathy. The average serum creatinine was 1.3 mg/dl (114.9 μmol/l); estimated glomerular filtration rate was 81.7 ml/min/1.73 m2 and urine protein to creatinine ratio was 1.08 g/g (122.0 mg/mmol). Males had greater podocyte vacuolization on light microscopy (mean score) and glycosphingolipid inclusions on semi-thin sections than females. Males also had significantly more proximal tubule, peritubular capillary and vascular intimal inclusions. Arteriolar hyalinosis was similar, but females had significantly more arterial hyalinosis. Chronic kidney disease stage correlated with arterial and glomerular sclerosis scores. Significant changes, including segmental and global sclerosis, and interstitial fibrosis were seen even in patients with stage 1–2 chronic kidney disease with minimal proteinuria. Conclusions. The development of a standardized scoring system of both disease-specific lesions, i.e. lipid deposition related, and general lesions of progression, i.e. fibrosis and sclerosis, showed a spectrum of histologic appearances even in early clinical stage of Fabry nephropathy. These findings support the role of kidney biopsy in the baseline evaluation of Fabry nephropathy, even with mild clinical disease. The scoring system will be useful for

  18. Fabry lens.

    NASA Technical Reports Server (NTRS)

    Michlovic, J.

    1972-01-01

    Discussion of the properties, operation, and applications of the Fabry lens. As used in stellar photometry, a Fabry lens is nothing more than a simple converging lens inserted into the optical train of a photometer to construct an image of the objective on the photomultiplier cathode. The thereby derived advantages are reviewed, and some techniques designed to maximize these advantages are outlined.

  19. Severe hypertrophic cardiomyopathy in a patient with atypical Anderson-Fabry disease.

    PubMed

    Masarone, Daniele; Duro, Giovanni; Dellegrottaglie, Santo; Colomba, Paolo; Rubino, Marta; Cirillo, Annapaola; Pisani, Antonio; Caiazza, Martina; Elliott, Perry Mark; Calabrò, Paolo; Pacileo, Giuseppe; Limongelli, Giuseppe

    2017-09-22

    Anderson-Fabry disease (AFD) is a hereditary disorder caused by a deficiency in the lysosomal enzyme α-galactosidase A which causes dysfunctions in multiple organ systems. Cardiac manifestation includes left ventricular hypertrophy, thickening of the valves, conduction disturbances and in the late phase, extensive areas of myocardial fibrosis with increased risk of sudden cardiac death. Case example: A case of AFD with exclusive cardiac involvement is described. During follow-up, due to the high risk of life-threatening arrhythmic events, implantation of an implantable cardioverter defibrillator is performed. AFD patients with advanced cardiac disease might represent a subgroup of patients who may require an implantable cardioverter defibrillator for primary prevention of sudden cardiac death.

  20. Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter-paper test: the FOCUS study.

    PubMed

    Hagège, Albert A; Caudron, Eric; Damy, Thibaud; Roudaut, Raymond; Millaire, Alain; Etchecopar-Chevreuil, Caroline; Tran, Thi-Chien; Jabbour, Firas; Boucly, Catherine; Prognon, Patrice; Charron, Philippe; Germain, Dominique P

    2011-01-01

    Patients with Fabry disease (FD) show left ventricular hypertrophy (LVH) mimicking hypertrophic cardiomyopathy (HCM) of sarcomeric origin and might benefit, if detected early, from specific enzyme replacement therapy. The prevalence of FD in patients with LVH of 13 mm or greater, screened using the leucocyte alpha-galactosidase A (α-gal A) activity test, a technique that is difficult to apply routinely, ranged from 0% to 6%. To screen systematically for FD in patients with a diagnosis of HCM (LVH ≥15 mm) in primary cardiology practice, a validated, physician-friendly α-gal A assay was used on dried blood spots using a filter paper test. A cohort of 392 adults (278 men) followed for HCM were screened for FD. A standard blood test was used for confirmation in nine men in whom the α-gal A result was 40% or less. Four men (1.5%; 1.8% of men ≥40 years vs 0% <40 years; all with α-gal A <30%), but no women, were diagnosed with FD. Index cases presented with diffuse but asymmetric LVH, with severe obstruction in one case and frequent high-grade atrioventricular conduction block necessitating a pacemaker in three cases. Family screening identified eight additional cases. Genotyping was performed successfully on DNA extracted from the filter papers. In male patients diagnosed as having HCM, pure FD cardiac variants are not exceptional and can be specifically identified using a simple filter-paper test. The sensitivity of this test is low in female patients.

  1. Evaluation of oxidative stress markers and cardiovascular risk factors in Fabry Disease patients

    PubMed Central

    Müller, Karen B.; Galdieri, Luciano C.; Pereira, Vanessa G.; Martins, Ana M.; D’Almeida, Vânia

    2012-01-01

    Fabry Disease, an X-linked inborn error of metabolism, is characterized by progressive renal insufficiency, with cardio and cerebrovascular involvement. Homocysteine (Hcy) is considered a risk factor for vascular diseases, but the mechanisms by which it produces cardiovascular damage are still poorly understood. Regarding the vascular involvement in FD patients, the analysis of factors related to thromboembolic events could be useful to improving our understanding of the disease. The aim of this study was to evaluate plasma Hcy and other parameters involved in the methionine cycle, as well as oxidative stress markers. The sample consisted of a group of 10 male FD patients and a control group of 8 healthy individuals, paired by age. Venous blood was collected for Hcy determination, molecular analysis, identification of thiobarbituric acid reactive substances, total glutathione and antioxidant enzymes activity, as well as vitamins quantification. Comparative analysis of FD patients versus the control group indicated hyperhomocysteinemia in 8 of the 10 FD patients, as well as a significant increase in overall glutathione levels and catalase activity. It is inferred that FD patients, apart from activation of the antioxidant system, present increased levels of plasma Hcy, although this is probably unrelated to common alterations in the methionine cycle. PMID:22888289

  2. Increased arterial diameters in the posterior cerebral circulation in men with Fabry disease.

    PubMed

    Uçeyler, Nurcan; Homola, György A; Guerrero González, Hans; Kramer, Daniela; Wanner, Christoph; Weidemann, Frank; Solymosi, László; Sommer, Claudia

    2014-01-01

    A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males-females; normal-impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity.

  3. Increased Arterial Diameters in the Posterior Cerebral Circulation in Men with Fabry Disease

    PubMed Central

    Üçeyler, Nurcan; Homola, György A.; Guerrero González, Hans; Kramer, Daniela; Wanner, Christoph; Weidemann, Frank; Solymosi, László; Sommer, Claudia

    2014-01-01

    A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males – females; normal – impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity. PMID:24475221

  4. Patent Foramen Ovale and Cryptogenic Strokes in the Stroke in Young Fabry Patients Study.

    PubMed

    Huber, Roman; Grittner, Ulrike; Weidemann, Frank; Thijs, Vincent; Tanislav, Christian; Enzinger, Christian; Fazekas, Franz; Wolf, Markus; Hennerici, Michael G; McCabe, Dominick J H; Putaala, Jukaa; Tatlisumak, Turgut; Kessler, Christoph; von Sarnowski, Bettina; Martus, Peter; Kolodny, Edwin; Norrving, Bo; Rolfs, Arndt

    2017-01-01

    A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO. We investigated the PFO prevalence in 3497 transient ischemic attack and ischemic stroke patients aged 18 to 55 years in the prospective multicenter SIFAP1 study (Stroke in Young Fabry Patients 1) using the ASCO classification. Patients without an obvious cause for transient ischemic attack/stroke (ASCO 0) were divided into subgroups with and without vascular risk factors (ASCO 0+ and 0-). In addition, we looked for PFO-related magnetic resonance imaging lesion patterns. PFO was identified in 25% of patients. Twenty percent of patients with a definite or probable cause of transient ischemic attack/stroke (≥1 grade 1 or 2 ASCO criterion; n=1769) had a PFO compared with 29% of cryptogenic stroke patients (ASCO 0 and 3; n=1728; P<0,001); subdivision of cryptogenic strokes revealed a PFO in 24% of 978 ASCO 3 patients (n.s. versus ASCO 1 and 2) and a higher prevalence of 36% in 750 ASCO 0 cases (P<0.001 versus ASCO 3 and versus ASCO 1 and 2). PFO was more commonly observed in ASCO 0- (n=271) than in ASCO 0+ patients (n=479; 48 versus 29%; P<0.001). There was no PFO-associated magnetic resonance imaging lesion pattern. Cryptogenic stroke patients demonstrate a heterogeneous PFO prevalence. Even in case of less conclusive diseases like nonstenotic arteriosclerosis, patients should preferentially be considered to have a non-PFO-mediated stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2016 American Heart Association, Inc.

  5. Ocular signs correlate well with disease severity and genotype in Fabry disease.

    PubMed

    Pitz, Susanne; Kalkum, Gisela; Arash, Laila; Karabul, Nesrin; Sodi, Andrea; Larroque, Sylvain; Beck, Michael; Gal, Andreas

    2015-01-01

    Ocular signs in Fabry disease have generally been regarded to be primarily of diagnostic value. We explored whether ocular findings, alone or in particular in combination with the α-galactosidase A gene mutation, have predictive value for disease severity. Data from the Fabry Outcome Survey (FOS), a large, global database sponsored by Shire, were selected for adult patients who had undergone ophthalmological examination. Three ocular signs were assessed: cornea verticillata, tortuous conjunctival and/or retinal vessels, and cataract. Fabry disease severity was measured using FOS Mainz Severity Score Index and modifications thereof. Ophthalmological data were available for 1203 (699 female, 504 male) adult patients with eye findings characteristic of Fabry disease in 55.1%. Cornea verticillata had a similar distribution in women (51.1%) and men (50.8%), whereas tortuous vessels and Fabry cataract were somewhat more frequent in men than in women. Patients with cornea verticillata, selected as the principal ocular sign for this study, had more severe disease (median score, 20.0) versus those without ocular signs (11.0; P<0.001). This finding could be confirmed by applying age adjusted severity scores. Moreover, the prevalence of cornea verticillata was significantly higher in patients with null (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01). Our analyses show a correlation between the prevalence of ocular changes in Fabry disease and disease severity. Consequently, information on ocular findings and α-galactosidase A gene mutation may help assess the risk for more severe Fabry disease. These observed findings are of notable clinical importance, as Fabry disease is characterized by high clinical course variability and only weak genotype-phenotype correlation at the individual patient level. Further confirmatory studies

  6. Impact of immunosuppressive therapy on therapy-neutralizing antibodies in transplanted patients with Fabry disease.

    PubMed

    Lenders, M; Oder, D; Nowak, A; Canaan-Kühl, S; Arash-Kaps, L; Drechsler, C; Schmitz, B; Nordbeck, P; Hennermann, J B; Kampmann, C; Reuter, S; Brand, S-M; Wanner, C; Brand, E

    2017-09-01

    Inhibitory antibodies towards enzyme replacement therapy (ERT) are associated with disease progression and poor outcome in affected male patients with lysosomal disorders such as Fabry disease (FD). However, little is known about the impact of immunosuppressive therapy on ERT inhibition in these patients with FD. In this retrospective study, we investigated the effect of long-term immunosuppression on ERT inhibition in male patients with FD (n = 26) receiving immunosuppressive therapy due to kidney (n = 24) or heart (n = 2) transplantation. No ERT-naïve transplanted patient (n = 8) developed antibodies within follow-up (80 ±72 months) after ERT initiation. Seven (26.9%) patients were tested ERT inhibition positive prior to transplantation. No de novo ERT inhibition was observed after transplantation (n = 18). In patients treated with high dosages of immunosuppressive medication such as prednisolone, tacrolimus and mycophenolate-mofetil/mycophenolate acid, ERT inhibition decreased after transplantation (n = 12; P = 0.0160). Tapering of immunosuppression (especially prednisolone) seemed to re-increase ERT inhibition (n = 4, median [range]: 16.6 [6.9; 36.9] %; P = 0.0972) over time. One ERT inhibition-positive patient required interventions with steroid therapy and increased doses of tacrolimus, which also lowered ERT inhibition. We conclude that the immunosuppressive maintenance therapy after transplantations seems to be sufficient to prevent de novo ERT inhibition in ERT-naïve patients. Intensified high dosages of immunosuppressive drugs are associated with decreased antibody titres and decreased ERT inhibition in affected patients, but did not result in long-term protection. Future studies are needed to establish ERT inhibition-specific immunosuppressive protocols with long-term modulating properties to warrant an improved disease course in ERT inhibition-positive males. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  7. Prevalence of chronic kidney disease in fabry disease patients: Multicenter cross sectional study in Argentina.

    PubMed

    Jaurretche, Sebastián; Antogiovanni, Norberto; Perreta, Fernando

    2017-09-01

    Nephropathy is one of the major complications of Fabry Disease (FD) and mainly includes reduced glomerular filtration rate (GFR) and proteinuria. Despite the frequency, scarce information exists regarding the frequency of CKD as well as other related complications in FD patients in Argentina. The aim of the study was to measure the prevalence of CKD at diagnosis of FD as well as to describe other related conditions in a large cohort of patients with FD. Methods: a cross-sectional study performed in three FD centers of Argentina during January 2014 and January 2016. Information at diagnosis regarding patient demographics, disease characteristics, key laboratory values, and renal, cardiac, cerebrovascular diseases and other related complications were collected. Results: A total of 60 patients were included. The mean age at diagnosis was 25.5 ± 16 years. 42% of included patients presented CKD in which the disease was mild (GFR ≥ 60 and < 90) in 60% (n = 15), moderate (GFR ≥ 30 and < 60) in 16% (n = 4), severe (GFR ≥ 15 and < 30) in 4% (n = 1) and failure (GFR < 15) in 20% (n = 5). Arrhythmias were reported for 13.3% of patients. In 33.3% the echocardiographic evaluation demonstrated left ventricular hypertrophy and peripheral neuropathy in 63.3%. Conclusion: This study presents information regarding the prevalence of CKD in a large cohort of FD patients at the moment of diagnosis in Argentina. Future studies will help us to confirm these initial findings.

  8. Fabry disease and cardiovascular involvement.

    PubMed

    Anastasakis, Aris; Papatheodorou, Efstathios; Steriotis, Alexandros Klavdios

    2013-01-01

    Fabry disease (FD, OMIM 301500) is a rare X-linked lysosomal storage disorder of the glycosphigolipid metabolism caused by total or partial deficiency of the lysosomal enzyme alpha-galactosidase A (α-gal A). Progressive intralysosomal accumulation of neutral glycosphingolipids in a variety of cell types triggers a cascade of pathophysiological events including cellular death, compromised energy metabolism, small vessel injury, K(Ca)3.1 channel dysfunction in endothelial cells, oxidative stress, impaired autophagosome maturation, tissue ischemia and, importantly, development of irreversible cardiac and renal tissue fibrosis, leading to major multisystemic manifestations. Cardiovascular complications of the disease are very frequent and contribute substantially to disease-related morbidity and mortality in men. Cardiovascular involvement is the leading cause of premature death in heterozygous female patients with FD. Left ventricular hypertrophy is the most prominent cardiac manifestation followed by conduction system disease, valve dysfunction, arrhythmias, vessel disease and coronary microvascular dysfunction. The diagnosis of subclinical forms of the disease, before the development of cardiac hypertrophy, using newer techniques (tissue doppler imaging, strain rate and cardiac magnetic resonance) is crucial to the early initation of the treatment. Greatest benefit of the enzyme replacement treatment is achieved when started at an early stage of the disease before extensive fibrosis or other irreversible tissue damage takes place. Fabry disease should be included in the differential diagnosis algorithm of idiopathic hypertrophy. Determination of Alpha-Gal A activity on plasma and peripheral leukocytes in males and genetic testing in females are the diagnostic gold-standards.

  9. Correlations between Endomyocardial Biopsies and Cardiac Manifestations in Taiwanese Patients with the Chinese Hotspot IVS4+919G>A Mutation: Data from the Fabry Outcome Survey.

    PubMed

    Hsu, Ting-Rong; Chang, Fu-Pang; Chu, Tzu-Hung; Sung, Shih-Hsien; Bizjajeva, Svetlana; Yu, Wen-Chung; Niu, Dau-Ming

    2017-01-09

    We retrospectively evaluated correlations between cardiac manifestations and globotriaosylceramide (Gb3) accumulation in cardiomyocytes from Taiwanese patients with Fabry disease and the IVS4+919G>A (IVS4) mutation who underwent endomyocardial biopsy (Shire; Fabry Outcome Survey data; extracted January 2015). Of 24 males and six females (median age [Q1; Q3] at biopsy 60.4 [57.4; 64.1] and 61.3 [60.4; 65.1] years, respectively), 13 males (54.2%) and five females (83.3%) received agalsidase alfa enzyme replacement therapy (ERT) before biopsy. Median left ventricular mass indexed to height (LVMI) within ±6 months of biopsy was 65.3 (52.7; 93.1) in males and 53.2 (42.0; 55.0) g/m(2.7) in females. A moderate, positive, statistically significant correlation was found between the percentage area Gb3 accumulation in cardiomyocytes and LVMI (Spearman's ρ, 0.45; p = 0.014); a smaller, positive, non-statistically significant correlation was observed between cardiomyocyte diameter and LVMI (Spearman's ρ 0.16, p = 0.394). Moderate, statistically significant, negative correlations were found between Gb3 accumulation and ERT duration (Spearman's ρ, -0.49, p = 0.007) and between cardiomyocyte size and ERT duration (Spearman's ρ, -0.37, p = 0.048). Longer ERT duration was associated with smaller amounts of Gb3 accumulation and smaller cardiomyocyte size. Further follow-up is recommended to confirm these trends in a larger sample size.

  10. Correlations between Endomyocardial Biopsies and Cardiac Manifestations in Taiwanese Patients with the Chinese Hotspot IVS4+919G>A Mutation: Data from the Fabry Outcome Survey

    PubMed Central

    Hsu, Ting-Rong; Chang, Fu-Pang; Chu, Tzu-Hung; Sung, Shih-Hsien; Bizjajeva, Svetlana; Yu, Wen-Chung; Niu, Dau-Ming

    2017-01-01

    We retrospectively evaluated correlations between cardiac manifestations and globotriaosylceramide (Gb3) accumulation in cardiomyocytes from Taiwanese patients with Fabry disease and the IVS4+919G>A (IVS4) mutation who underwent endomyocardial biopsy (Shire; Fabry Outcome Survey data; extracted January 2015). Of 24 males and six females (median age [Q1; Q3] at biopsy 60.4 [57.4; 64.1] and 61.3 [60.4; 65.1] years, respectively), 13 males (54.2%) and five females (83.3%) received agalsidase alfa enzyme replacement therapy (ERT) before biopsy. Median left ventricular mass indexed to height (LVMI) within ±6 months of biopsy was 65.3 (52.7; 93.1) in males and 53.2 (42.0; 55.0) g/m2.7 in females. A moderate, positive, statistically significant correlation was found between the percentage area Gb3 accumulation in cardiomyocytes and LVMI (Spearman’s ρ, 0.45; p = 0.014); a smaller, positive, non-statistically significant correlation was observed between cardiomyocyte diameter and LVMI (Spearman’s ρ 0.16, p = 0.394). Moderate, statistically significant, negative correlations were found between Gb3 accumulation and ERT duration (Spearman’s ρ, −0.49, p = 0.007) and between cardiomyocyte size and ERT duration (Spearman’s ρ, −0.37, p = 0.048). Longer ERT duration was associated with smaller amounts of Gb3 accumulation and smaller cardiomyocyte size. Further follow-up is recommended to confirm these trends in a larger sample size. PMID:28075357

  11. Amelioration of serum 8-OHdG level by enzyme replacement therapy in patients with Fabry cardiomyopathy.

    PubMed

    Chen, Kuan-Hsuan; Chou, Yueh-Ching; Hsiao, Chen-Yuan; Chien, Yueh; Wang, Kang-Ling; Lai, Ying-Hsiu; Chang, Yuh-Lih; Niu, Dau-Ming; Yu, Wen-Chung

    2017-04-29

    The level of 8-hydroxy-2-deoxyguanosise (8-OHdG) is a marker of oxidative stress. The objective of this study was to evaluate the effect of enzyme replacement therapy (ERT) on the level of 8-OHdG in patients with Fabry cardiomyopathy and the clinical evolution of Fabry cardiomyopathy. We measured the serum levels of 8-OHdG in 20 healthy control and 22 patients with Fabry cardiomyopathy before and after ERT. The mean lysoGb3 and 8-OHdG levels was significantly increased in patients with Fabry cardiomyopathy compared with that of control subjects (lysoGb3, 3.6 ± 1.1 nM vs. 0.4 ± 0.1 nM, p < 0.01; 8-OHdG, 4.5 ± 0.5 ng/mL vs. 3.4 ± 0.4 ng/mL, P < 0.05). The mean lysoGb3 and 8-OHdG levels was significantly reduced after ERT for 14.2 months (lysoGb3, 3.6 ± 1.1 nM vs. 2.9 ± 1.1 nM, P < 0.05; 8-OHdG, 4.5 ± 0.5 ng/mL to 4 ± 0.4 ng/mL, P < 0.05). These changes were accompanied by decreases in LVM and LVMI. We demonstrated that the serum 8-OHdG levels is increased in patients with Fabry cardiomyopathy (FC) and that successful management of FC with ERT is associated with a decrease in this oxidative stress marker. Serum 8-OHdG levels can be used not only as a noninvasive biomarker of oxidative stress in patients with FC but also an objective and quantitative parameter in the follow-up of patients during ERT. Copyright © 2017. Published by Elsevier Inc.

  12. Fabry disease: thirty-five mutations in the alpha-galactosidase A gene in patients with classic and variant phenotypes.

    PubMed Central

    Eng, C. M.; Ashley, G. A.; Burgert, T. S.; Enriquez, A. L.; D'Souza, M.; Desnick, R. J.

    1997-01-01

    BACKGROUND: Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A (alpha-Gal A) gene located at Xq22.1. To determine the nature and frequency of the molecular lesions causing the classical and milder variant Fabry phenotypes and for precise carrier detection, the alpha-Gal A lesions in 42 unrelated Fabry hemizygotes were determined. MATERIALS AND METHODS: Genomic DNA was isolated from affected probands and their family members. The seven alpha-galactosidase A exons and flanking intronic sequences were PCR amplified and the nucleotide sequence was determined by solid-phase direct sequencing. RESULTS: Two patients with the mild cardiac phenotype had missense mutations, I9IT and F113L, respectively. In 38 classically affected patients, 33 new mutations were identified including 20 missense (MIT, A31V, H46R, Y86C, L89P, D92Y, C94Y, A97V, R100T, Y134S, G138R, A143T, S148R, G163V, D170V, C202Y, Y216D, N263S, W287C, and N298S), two nonsense (Q386X, W399X), one splice site mutation (IVS4 + 2T-->C), and eight small exonic insertions or deletions (304del1, 613del9, 777del1, 1057del2, 1074del2, 1077del1, 1212del3, and 1094ins1), which identified exon 7 as a region prone to gene rearrangements. In addition, two unique complex rearrangements consisting of contiguous small insertions and deletions were found in exons 1 and 2 causing L45R/H46S and L120X, respectively. CONCLUSIONS: These studies further define the heterogeneity of mutations causing Fabry disease, permit precise carrier identification and prenatal diagnosis in these families, and facilitate the identification of candidates for enzyme replacement therapy. Images FIG. 2 PMID:9100224

  13. Intraoperative Diagnosis of Anderson-Fabry Disease in Patients With Obstructive Hypertrophic Cardiomyopathy Undergoing Surgical Myectomy.

    PubMed

    Cecchi, Franco; Iascone, Maria; Maurizi, Niccolò; Pezzoli, Laura; Binaco, Irene; Biagini, Elena; Fibbi, Maria Laura; Olivotto, Iacopo; Pieruzzi, Federico; Fruntelata, Ana; Dorobantu, Lucian; Rapezzi, Claudio; Ferrazzi, Paolo

    2017-08-09

    Diagnostic screening for Anderson-Fabry cardiomyopathy (AFC) is performed in the presence of specific clinical red flags in patients with hypertrophic cardiomyopathy (HCM) older than 25 years. However, left ventricular outflow tract obstruction (LVOTO) has been traditionally considered an exclusion criteria for AFC. To examine a series of patients diagnosed with HCM and severe basal LVOTO undergoing myectomy in whom the diagnosis of AFC was suspected by the cardiac surgeon intraoperatively and confirmed by histological and genetic examinations. This retrospective analysis of patients undergoing surgical septal reduction strategies was conducted in 3 European tertiary referral centers for HCM from July 2013 to December 2016. Patients with a clinical diagnosis of obstructive HCM referred for surgical management of LVOTO were observed for at least 18 months after the procedure (mean [SD] follow-up, 33 [14] months). Etiology of patients with HCM who underwent surgical myectomy. From 2013, 235 consecutive patients with a clinical diagnosis of HCM underwent septal myectomy. The cardiac surgeon suspected a storage disease in 3 patients (1.3%) while inspecting their heart samples extracted from myectomy. The mean (SD) age at diagnosis for these 3 patients was 42 (4) years; all were male. None of the 3 patients presented with extracardiac features suggestive of AFC. All patients showed asymmetrical left ventricular hypertrophy, with maximal left ventricular thickness in the basal septum (19-31 mm), severe basal LVOTO (70-120 mm Hg), and left atrial dilatation (44-57 mm). Only 1 patient presented with late gadolinium enhancement on cardiovascular magnetic resonance at the right ventricle insertion site. The mean (SD) age at surgical procedure was 63 (5) years. On tactile sensation, the surgeon felt a spongy consistency of the surgical samples, different from the usual stony-elastic consistency typical of classic HCM, and this prompted histological examinations. Histology

  14. Screening, diagnosis, and management of patients with Fabry disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

    PubMed

    Schiffmann, Raphael; Hughes, Derralynn A; Linthorst, Gabor E; Ortiz, Alberto; Svarstad, Einar; Warnock, David G; West, Michael L; Wanner, Christoph

    2017-02-01

    Patients with Fabry disease (FD) are at a high risk for developing chronic kidney disease and cardiovascular disease. The availability of specific but costly therapy has elevated the profile of this rare condition. This KDIGO conference addressed controversial areas in the diagnosis, screening, and management of FD, and included enzyme replacement therapy and nonspecific standard-of-care therapy for the various manifestations of FD. Despite marked advances in patient care and improved overall outlook, there is a need to better understand the pathogenesis of this glycosphingolipidosis and to determine the appropriate age to initiate therapy in all types of patients. The need to develop more effective specific therapies was also emphasized.

  15. Clinical Features, Diagnosis, and Management of Patients With Anderson-Fabry Cardiomyopathy.

    PubMed

    Yogasundaram, Haran; Kim, Daniel; Oudit, Omar; Thompson, Richard B; Weidemann, Frank; Oudit, Gavin Y

    2017-07-01

    Anderson-Fabry disease (AFD) is an X-linked recessive, multisystem disease of lysosomal storage. A mutation in the gene encoding the hydrolase enzyme α-galactosidase A results in its deficiency, or complete absence of activity. Subsequent progressive intracellular accumulation of glycosphingolipids, predominantly globotriaosylceramide, in various tissues, results in progressive organ dysfunction and failure, most commonly affecting the kidneys, nervous system, skin, eyes, vascular endothelium, and the heart. Cardiac involvement in AFD represents a leading cause of morbidity and mortality. Globotriaosylceramide accumulation affects cardiomyocytes, smooth muscle cells, vascular endothelial cells, and fibroblasts leading to various pathologies including valvular regurgitation, conduction disease and arrhythmias, coronary microvascular dysfunction, and right and left ventricular hypertrophy (LVH) leading to early diastolic dysfunction and late-stage systolic impairment. Diagnosis is on the basis of decreased plasma α-galactosidase activity in men and positive genetic testing in women. Contemporary large-scale screening studies have revealed a prevalence of 1%-5% in patients with unexplained LVH in multiple cohorts. Cardiac magnetic resonance imaging, with its unique tissue characterization capabilities, is the most important imaging modality to assess for cardiomyopathy in patients with AFD. Enzyme replacement therapy is indicated in AFD patients with significant organ involvement, and has been shown to clear sphingolipids from endothelial cells in other organs, as well as to reduce left ventricular mass as early as 6 months after starting treatment. There is increasing evidence that enzyme replacement therapy might be more effective if given at earlier stages of disease, before the development of LVH and myocardial fibrosis. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  16. Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease.

    PubMed

    Rombach, S M; Dekker, N; Bouwman, M G; Linthorst, G E; Zwinderman, A H; Wijburg, F A; Kuiper, S; Vd Bergh Weerman, M A; Groener, J E M; Poorthuis, B J; Hollak, C E M; Aerts, J M F G

    2010-09-01

    Fabry disease is an X-linked lysosomal storage disorder due to deficiency of alpha-Galactosidase A, causing accumulation of globotriaosylceramide and elevated plasma globotriaosylsphingosine (lysoGb3). The diagnostic value and clinical relevance of plasma lysoGb3 concentration was investigated. All male and adult female patients with classical Fabry disease could be discerned by an elevated plasma lysoGb3. In young pre-symptomatic Fabry heterozygotes, lysoGb3 levels can be normal. Individuals carrying the R112H and P60L mutations, without classical Fabry symptoms, showed no elevated plasma lysoGb3. Multiple regression analysis showed that there is no correlation of plasma lysoGb3 concentration with total disease severity score in Fabry males. However, plasma lysoGb3 concentration did correlate with white matter lesions (odds ratio: 6.1 per 100 nM lysoGb3 increase (95% CI: 1.4-25.9, p=0.015). In females, plasma lysoGb3 concentration correlated with overall disease severity. Furthermore, plasma lysoGb3 level was related to left ventricular mass (19.5+/-5.5 g increase per 10 nM lysoGb3 increase; p=0.001). In addition, it was assessed whether lifetime exposure to lysoGb3 correlates with disease manifestations. Male Fabry patients with a high lysoGb3 exposure (>10,000 U), were moderately or severely affected, only one mildly. Female patients with a low exposure (<1000 U) were asymptomatic or mildly affected. A large proportion of the females with an exposure >1000 U showed disease complications. Plasma lysoGb3 is useful for the diagnosis of Fabry disease. LysoGb3 is an independent risk factor for development of cerebrovascular white matter lesions in male patients and left ventricular hypertrophy in females. Disease severity correlates with exposure to plasma lysoGb3.

  17. Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors.

    PubMed

    Bennett, Robin L; Hart, Kimberly A; O'Rourke, Erin; Barranger, John A; Johnson, Jack; MacDermot, Kay D; Pastores, Gregory M; Steiner, Robert D; Thadhani, Ravi

    2002-04-01

    The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing and interpretation of results, psychosocial considerations, and references for professional and patient resources. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a healthcare provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.

  18. Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

    PubMed

    Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank; Brand, Eva

    2016-03-01

    Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used.

  19. Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-Up

    PubMed Central

    Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank

    2016-01-01

    Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3–0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C–based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. PMID:26185201

  20. Brain magnetic resonance imaging findings fail to suspect Fabry disease in young patients with an acute cerebrovascular event.

    PubMed

    Fazekas, Franz; Enzinger, Christian; Schmidt, Reinhold; Grittner, Ulrike; Giese, Anne-Katrin; Hennerici, Michael G; Huber, Roman; Jungehulsing, Gerhard J; Kaps, Manfred; Kessler, Christof; Martus, Peter; Putaala, Jukka; Ropele, Stefan; Tanislav, Christian; Tatlisumak, Turgut; Thijs, Vincent; von Sarnowski, Bettina; Norrving, Bo; Rolfs, Arndt

    2015-06-01

    Fabry disease (FD) may cause stroke and is reportedly associated with typical brain findings on magnetic resonance imaging (MRI). In a large group of young patients with an acute cerebrovascular event, we wanted to test whether brain MRI findings can serve to suggest the presence of FD. The Stroke in Young Fabry Patients (SIFAP 1) study prospectively collected clinical, laboratory, and radiological data of 5023 patients (18-55 years) with an acute cerebrovascular event. Their MRI was interpreted centrally and blinded to all other information. Biochemical findings and genetic testing served to diagnose FD in 45 (0.9%) patients. We compared the imaging findings between FD and non-FD patients in patients with at least a T2-weighted MRI of good quality. A total of 3203 (63.8%) patients had the required MRI data set. Among those were 34 patients with a diagnosis of FD (1.1%), which was definite in 21 and probable in 13 cases. The median age of patients with FD was slightly lower (45 versus 46 years) and women prevailed (70.6% versus 40.7%; P<0.001). Presence or extent of white matter hyperintensities, infarct localization, vertebrobasilar artery dilatation, T1-signal hyperintensity of the pulvinar thalami, or any other MRI finding did not distinguish patients with FD from non-FD cerebrovascular event patients. Pulvinar hyperintensity was not present in a single patient with FD but seen in 6 non-FD patients. Brain MRI findings cannot serve to suspect FD in young patients presenting with an acute cerebrovascular event. This deserves consideration in the search for possible causes of young patients with stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2015 American Heart Association, Inc.

  1. Ventricular Tachycardia in Fabry Disease Detected in a 50-Year-Old Woman during 14-Day Continuous Cardiac Monitoring

    PubMed Central

    Silva-Gburek, Jaime; Rochford, Laura; Hopkin, Robert

    2016-01-01

    Fabry disease is an X-linked lysosomal storage disorder. Female carriers were long thought to be asymptomatic; however, research has revealed the opposite. Cardiac conditions are the chief causes of death in women with Fabry disease. Although ventricular tachycardia has been reported in male patients with Fabry disease, it is not thought to be a frequent finding in females. We describe the case of a 50-year-old woman in whom we used 14-day continuous electrocardiographic monitoring to identify nonsustained ventricular tachycardia, after electrocardiograms and 24-hour Holter monitoring failed to detect the arrhythmia. A permanent implantable cardioverter-defibrillator relieved the patient's symptoms. We discuss why this case supports the need for more extensive electrophysiologic evaluation in women who have Fabry disease. PMID:28100976

  2. Early markers of Fabry disease revealed by proteomics.

    PubMed

    Matafora, V; Cuccurullo, M; Beneduci, A; Petrazzuolo, O; Simeone, A; Anastasio, P; Mignani, R; Feriozzi, S; Pisani, A; Comotti, C; Bachi, A; Capasso, G

    2015-06-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase α-galactosidase A (α-GalA) that leads to the intra-lysosomal accumulation of globotriaosylceramide (Gb3) in various organ systems. As a consequence, a multisystems disorder develops, culminating in stroke, progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though the monitoring of treatment is hindered by a lack of surrogate markers of response. Remarkably, due to the high heterogeneity of the Fabry phenotype, both diagnostic testing and treatment decisions are more challenging in females than in males; thus, reliable biomarkers for Fabry disease are needed, particularly for female patients. Here, we use a proteomic approach for the identification of disease-associated markers that can be used for the early diagnosis of FD as well as for monitoring the effectiveness of ERT. Our data show that the urinary proteome of Fabry naïve patients is different from that of normal subjects. In addition, biological pathways mainly affected by FD are related to immune response, inflammation, and energetic metabolism. In particular, the up-regulation of uromodulin, prostaglandin H2 d-isomerase and prosaposin in the urine of FD patients was demonstrated; these proteins might be involved in kidney damage at the tubular level, inflammation and immune response. Furthermore, comparing the expression of these proteins in Fabry patients before and after ERT treatment, a decrease of their concentration was observed, thus demonstrating the correlation between the identified markers and the effectiveness of the pharmacological treatment.

  3. Auditing the frequency and the clinical and economic impact of testing for Fabry disease in patients under the age of 70 with a stroke admitted to Saint Vincent's University Hospital over a 6-month period.

    PubMed

    Lambe, J; Noone, I; Lonergan, R; Tubridy, N

    2017-05-03

    Fabry disease is an X-linked recessive lysosomal storage disorder that provokes multi-organ morbidity, including early-onset stroke. Worldwide prevalence may be greater than previously estimated, with many experiencing first stroke prior to diagnosis of Fabry disease. The aim of this study is to screen a cohort of stroke patients under 70 years of age, evaluating the clinical and economic efficacy of such a broad screening programme for Fabry disease. All stroke patients under 70 years of age who were entered into the Saint Vincent's University Hospital stroke database over a 6-month period underwent enzyme analysis and/or genetic testing as appropriate for Fabry disease. Patients' past medical histories were analysed for clinical signs suggestive of Fabry disease. Cost-effectiveness analysis of testing was performed and compared to overall economic impact of young stroke in Ireland. Of 22 patients tested for Fabry disease, no new cases were detected. Few clinical indicators of Fabry disease were identified at the time of testing. Broad screening programmes for Fabry disease are highly unlikely to offset the cost of testing. The efficacy of future screening programmes will depend on careful selection of an appropriate patient cohort of young stroke patients with multi-organ morbidity and a positive family history.

  4. Urinary total globotriaosylceramide and isoforms to identify women with Fabry disease: a diagnostic test study.

    PubMed

    Paschke, Eduard; Fauler, Guenter; Winkler, Heimo; Schlagenhauf, Axel; Plecko, Barbara; Erwa, Wolfgang; Breunig, Frank; Urban, Wolfgang; Vujkovac, Bojan; Sunder-Plassmann, Gere; Kotanko, Peter

    2011-05-01

    Fabry disease is a treatable X-linked lysosomal storage disorder caused by alterations in the structural gene (GLA) of α-galactosidase A (AGAL), manifesting with cardiovascular and/or kidney disease and decreased life span. Although males as well as females can be affected, females cannot be identified using AGAL activity. We evaluated urinary total globotriaosylceramide (Gb3) and single N-acyl isoforms for the detection of Fabry disease in female patients with and without chronic kidney disease (CKD). Diagnostic accuracy study. 28 untreated women with Fabry disease and 335 female outpatients without Fabry disease with (n = 213) and without CKD (n = 122). Assessment of urinary Gb3 using electrospray ionization tandem mass spectrometry, including 6 N-acyl isoforms, total Gb3 related to urinary creatinine, and ratios of Gb3-24 to Gb3-18 and Gb3-24 to urinary AGAL. Fabry disease, diagnosed by identification of known pathogenic GLA mutations in patients or their male relatives. 6 parameters (ratio of Gb3-24 to urinary AGAL activity; Gb3-24; ratio of Gb3-24 to Gb3-18; Gb3-22; Gb3-16; and total Gb3) were highly informative for the diagnosis of Fabry disease independent of the presence or absence of CKD (area under the receiver operating characteristic curve, 0.876-0.927; all P < 0.001). Because of low signal-to-noise ratios, 15.8% of samples had to be excluded. Total urinary Gb3 and Gb3 isoforms can be used for the diagnosis of Fabry disease in women. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  5. Control of proteinuria with increased doses of agalsidase alfa in a patient with Fabry disease with atypical genotype-phenotype expression.

    PubMed

    Paliouras, Christos; Aperis, Georgios; Lamprianou, Foteini; Ntetskas, Giorgos; Roufas, Konstantinos; Alivanis, Polichronis

    2015-01-01

    Fabry disease is a rare X-linked lysosomal storage disorder of glycosphingolipids, caused by the partial or complete deficiency of the lysosomal enzyme alpha-galactosidase A (a-Gal A). The missense mutation pN215S usually causes a milder form of the disease with isolated cardiac involvement. We report a case of a male Fabry patient with the pN215S mutation and a generalized disease. He suffered a relapse in proteinuria which responded to increased doses of the administered recombinant enzyme. Individualization of enzyme replacement therapy must be considered in selected cases characterized by clinical deterioration.

  6. The Coexistence of Multiple Myeloma-associated Amyloid Light-chain Amyloidosis and Fabry Disease in a Hemodialysis Patient.

    PubMed

    Taguchi, Kensei; Moriyama, Atsuo; Kodama, Goh; Nakayama, Yosuke; Fukami, Kei

    2017-01-01

    Fabry disease (FD) is an inherited lysosomal disorder caused by an X-linked α-galactosidase A deficiency. We report the case of a 50-year-old male FD patient on hemodialysis who presented with macroglossia-related speaking difficulty and gastrointestinal symptoms. An endoscopic analysis revealed multiple gastric ulcers, and a histological examination led to a diagnosis of amyloid light-chain amyloidosis. Serum free light-chain and bone marrow analyses detected multiple myeloma (MM). Treatment with bortezomib and dexamethasone significantly improved the patient's symptoms. This is the first case to demonstrate a potential pathogenic relationship between FD and MM. The similar gastrointestinal manifestations might have contributed to the diagnostic difficulty.

  7. The management and treatment of children with Fabry disease: A United States-based perspective.

    PubMed

    Hopkin, Robert J; Jefferies, John L; Laney, Dawn A; Lawson, Victoria H; Mauer, Michael; Taylor, Matthew R; Wilcox, William R

    2016-02-01

    Fabry disease is an inherited X-linked disorder that presents during childhood in male and female patients. Young patients may initially experience pain, hypohidrosis, and gastrointestinal symptoms. Other manifestations of Fabry disease, such as renal and cardiac disease, manifest later in adolescence or adulthood. In the pediatric population, renal damage is typically subclinical and identifiable only through biopsy. Specialists from the United States with expertise in Fabry disease convened during 2013-2014 in order to develop these consensus guidelines about the management and treatment of children with Fabry disease. The presence of symptoms in boys and girls of any age is an indication to begin therapy. Early treatment before the onset of potentially irreversible vital organ pathology is ideal. Asymptomatic children with Fabry mutations should be followed closely for the development of renal, cardiac, neurological, or gastrointestinal signs, symptoms, or laboratory changes, which would warrant treatment initiation. A comprehensive care plan should be implemented by the treating physicians to guide the management of children with Fabry disease.

  8. Early diastolic mitral annular velocity and color M-mode flow propagation velocity in the evaluation of left ventricular diastolic function in patients with Fabry disease.

    PubMed

    Palecek, Tomas; Linhart, Ales; Lubanda, Jean Claude; Magage, Sudheera; Karetova, Debora; Bultas, Jan; Aschermann, Michael

    2006-01-01

    Fabry disease is an X-linked genetic disorder characterized by progressive intracellular accumulation of neutral glycosphingolipids. Cardiac involvement is frequent and left ventricular (LV) diastolic dysfunction is present in most of the affected subjects. Pulsed-wave tissue Doppler echocardiography (PW-TDE) and color M-mode are new Doppler methods for LV diastolic function evaluation. Their role in the assessment of Fabry disease-related cardiomyopathy remains to be established. In this study we aimed to determine the utility of PW-TDE and color M-mode-derived parameters in the assessment of LV diastolic function in patients with Fabry disease. Eighty-one echocardiographic examinations performed in 35 patients affected by Fabry disease were retrospectively analyzed. Early diastolic lateral mitral annular velocity (E(m)) determined by PW-TDE and color M-mode flow propagation velocity (V(p)) were measured and compared to LV filling patterns obtained using standard Doppler indexes. The receiver operating characteristics (ROC) curves method was used to determine the summary measure of relative accuracy for E(m) and V(p). A comparison of ROC curves showed a significant difference for areas under the curve in favor of E(m) (P < 0.001). Pseudonormal filling pattern, higher LV mass index, higher relative wall thickness, larger left atrial diameter, and older age were more frequent (all P < 0.001) in patients with incorrect diagnosis of normal LV diastolic function based on the measurement of V(p). E(m) appears to be superior to V(p) in the assessment of LV diastolic function in patients with Fabry disease. V(p) fails to detect abnormal LV diastolic function in subjects with pronounced concentric LV remodeling and pseudonormal filling pattern.

  9. Mutations of the GLA gene in Korean patients with Fabry disease and frequency of the E66Q allele as a functional variant in Korean newborns.

    PubMed

    Lee, Beom Hee; Heo, Sun Hee; Kim, Gu-Hwan; Park, Jung-Young; Kim, Woo-Shik; Kang, Duk-Hee; Choe, Kyung Hoon; Kim, Won-Ho; Yang, Song Hyun; Yoo, Han-Wook

    2010-08-01

    Fabry disease is caused by an alpha-galactosidase A (GLA) deficiency. In this study, we identified 28 unrelated Korean families with Fabry disease with 25 distinct mutations in the GLA gene including six novel mutations (p.W47X, p.C90X, p.D61EfsX32, IVS4(-11)T>A, p.D322E and p.W349). Notably, five subjects from four unrelated families carried the p.E66Q variant, previously known as a pathogenic mutation in atypical Fabry disease. Among these patients, only one had proteinuria and two had hypertrophic cardiomyopathy without any other systemic manifestation of Fabry disease. Substantial residual GLA activity was shown both in the leukocytes of p.E66Q patients (19.0-30.3% of normal activity) and in transiently overexpressed COS-7 cells (43.8 + or - 3.03% of normal activity). Although GLA harboring p.E66Q is unstable at neutral pH, the enzyme is efficiently expressed in the lysosomes of COS-7 cells. The location of p.E66 is distant from both the active site and the dimer interface, and has a more accessible surface area than have other mutations of atypical Fabry disease. In addition, the allele frequency of p.E66Q determined in 833 unrelated Korean individuals was remarkably high at 1.046% (95% confidence interval, 0.458-1.634%). These results indicate that p.E66Q is a functional polymorphism rather than a pathogenic mutation.

  10. Enzyme replacement therapy and Fabry nephropathy.

    PubMed

    Warnock, David G; Daina, Erica; Remuzzi, Giuseppe; West, Michael

    2010-02-01

    Involvement of the kidneys in Fabry disease ("nephropathy") occurs in male and female individuals. The majority of patients with progressive nephropathy will have significant proteinuria and develop progressive loss of kidney function, leading to ESRD. All too often, treating physicians may ignore "normal" serum creatinine levels or "minimal" proteinuria and fail to assess properly the severity of kidney involvement and institute appropriate management. Fabry nephropathy is treatable, even in patients with fairly advanced disease. Although the cornerstone of therapy remains enzyme replacement therapy with agalsidase, this treatment alone does not reduce urine protein excretion. Treatment with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors must be added to enzyme replacement therapy to reduce urine protein excretion with the hope that this will stabilize kidney function. Kidney function, with at least estimated GFR based on serum creatinine and measurements of urinary protein, should be measured at every clinic visit, and the rate of change of the estimated GFR should be followed over time. Antiproteinuric therapy can be dosed to a prespecified urine protein target rather than a specific BP goal, with the proviso that successful therapy will usually lower the BP below the goal of 130/80 mmHg that is used for other forms of kidney disease. The overall goal for treating Fabry nephropathy is to reduce the rate of loss of GFR to -1 ml/min per 1.73 m(2)/yr, which is that seen in the normal adult population. A systematic approach is presented for reaching this goal in the individual patient.

  11. Sudoscan as a noninvasive tool to assess sudomotor dysfunction in patients with Fabry disease: results from a case–control study

    PubMed Central

    Sahuc, Pauline; Chiche, Laurent; Dussol, Bertrand; Pouget, Jean; Franques, Jérôme

    2016-01-01

    Hypohidrosis is a frequent and early symptom in patients with Fabry disease. Studies have reported improved sweating in patients treated with enzyme-replacement therapy. A new method, Sudoscan, has been developed that is noninvasive, is quantitative, and can quickly evaluate sweat gland function. It is based on the electrochemical reaction between sweat chlorides and stainless-steel electrodes in contact with the palms and soles. The aim of our study was to evaluate the Sudoscan as a tool to assess sudomotor dysfunction in patients with Fabry disease. Consecutive patients were prospectively recruited who had a diagnosis of Fabry disease, which had been confirmed genetically and/or by measurement of α-galactosidase activity in leukocytes. Healthy controls, matched (1:1) for age and sex, were also enrolled. Test results were expressed immediately as electrochemical skin conductance (ESC, µS) for hands and feet. Sudomotor dysfunction was considered absent, moderate, or severe if the ESC measured on the feet was >60 µS, between 60 and 40 µS, or <40 µS, respectively. Among the 18 patients, 11 had hypohidrosis or anhidrosis. Hand and feet ESCs were significantly lower in patients compared to their controls (P=0.0015 and P=0.0047, respectively). Among patients, 8/18 (44.5%) had a sudomotor dysfunction, moderate in three and severe in five cases. Hand and feet ESCs were significantly lower in those with hypohidrosis/anhidrosis compared to those without (P=0.0014 and P=0.0056, respectively). This study showed that Sudoscan provided a quick, noninvasive, and quantitative measurement of sudomotor function in Fabry disease patients. PMID:26893567

  12. Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development

    PubMed Central

    Biko, Lydia; Hose, Dorothea; Hofmann, Lukas; Sommer, Claudia

    2016-01-01

    Background Fabry disease is an X-linked lysosomal storage disorder due to impaired activity of alpha-galactosidase A with intracellular accumulation of globotriaosylceramide. Associated small fiber pathology leads to characteristic pain in Fabry disease. We systematically assessed sensory system, physical activity, metabolic parameters, and morphology of male and female mice with alpha-galactosidase A deficiency (Fabry ko) from 2 to 27 months of age and compared results with those of age- and gender-matched wild-type littermates of C57Bl/6J background. Results From the age of two months, male and female Fabry mice showed mechanical hypersensitivity (p < 0.001 each) compared to wild-type littermates. Young Fabry ko mice of both genders were hypersensitive to heat stimulation (p < 0.01) and developed heat hyposensitivity with aging (p < 0.05), while cold hyposensitivity was present constantly in young (p < 0.01) and old (p < 0.05) Fabry ko mice compared to wild-type littermates. Stride angle increased only in male Fabry ko mice with aging (p < 0.01) in comparison to wild-type littermates. Except for young female mice, male (p < 0.05) and female (p < 0.01) Fabry ko mice had a higher body weight than wild-type littermates. Old male Fabry ko mice were physically less active than their wild-type littermates (p < 0.05), had lower chow intake (p < 0.001), and lost more weight (p < 0.001) in a one-week treadmill experiment than wild-type littermates. Also, Fabry ko mice showed spontaneous pain protective behavior and developed orofacial dysmorphism resembling patients with Fabry disease. Conclusions Mice with alpha-galactosidase A deficiency show age-dependent and distinct deficits of the sensory system. alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain. PMID:27145802

  13. Coexistence of Fabry Disease and Membranous Nephropathy.

    PubMed

    Liu, Ying; Xie, Hua; Lin, Hongli; Chen, Shuni; Wang, Weidong; Zhao, Guangben; Zhang, Xu

    2016-01-01

    A 21-year-old man with no family history or characteristic symptoms of Fabry disease presented with proteinuria. Histological and immunofluorescent analysis of kidney tissue collected revealed stage 1 membranous nephropathy. Electron microscopy of the same tissue revealed a large number of myeloid bodies (zebra bodies) in the glomerular epithelial cytoplasm and a mild irregular thickening of basement membrane. A diagnosis of Fabry disease was supported by the low α-galactosidase A activity detected in the patient's plasma, and confirmed by the detection of a pathogenic homozygous mutation in the α-galactosidase A gene. Therefore, the final diagnosis was of coexistent Fabry disease and stage 1 membranous nephropathy. This is the first case study reporting the coexistence of Fabry disease and membranous nephropathy. Our results emphasize the importance of electron microscopy in Fabry disease diagnosis.

  14. The pathophysiology of Fabry disease.

    PubMed

    Olivera-González, S; Josa-Laorden, C; Torralba-Cabeza, M A

    2017-08-23

    Fabry disease is a lysosomal condition with systemic clinical expression, caused by the tissue deposit of globotriaosylceramide, due to a deficit in its degradation. As with most lysosomal diseases, the presence of a mutation in a gene does not explain the pathophysiological disorders shown by patients. We conducted a comprehensive review of the pathogenic mechanisms that occur in Fabry disease. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  15. Electrocardiographic Changes and Arrhythmia in Fabry Disease

    PubMed Central

    Namdar, Mehdi

    2016-01-01

    Fabry disease is an X-chromosome-linked lysosomal storage disease characterized by a deficient activity or, in most males, absence of the enzyme α-galactosidase A (a-Gal A) leading to systemic, primary lysosomal accumulation of globotriaosylceramide (Gb3) (1). Recent literature refers to an overall birth prevalence of 1:40,000–170,000; however, such data do not allow an estimation on an actual patient number suffering from Fabry disease (2). Multisystem morbidity commonly develops in childhood and, with progression of the disease, life-threatening complications often occur in adulthood, including renal failure, cardiovascular dysfunction, neuropathy, and stroke (3–6). Life expectancy is reduced by an average of 15 years in female patients and 20 years in male patients (7, 8). The pathognomonic Gb3 accumulation has been repeatedly observed over the past decades by many groups in vascular endothelial and smooth muscle cells, cardiomyocytes, cardiac conduction tissue, and valvular fibroblasts (3). Although incompletely described, it is likely that inflammatory and neurohormonal mechanisms are involved in subsequent cellular and vascular dysfunction, leading to tissue ischemia, hypertrophy, and fibrosis (9). Furthermore, recently published works on cardiomyocyte dysfunction and conduction tissue involvement have suggested that cardiac dysfunction may reflect increased myocardial nitric oxide production with oxidative damage of cardiomyocyte myofilaments and DNA, causing cell dysfunction and death, and accelerated conduction with prolonged refractoriness and electric instability (10, 11). PMID:27047943

  16. Globotriaosylsphingosine (lyso-Gb3) might not be a reliable marker for monitoring the long-term therapeutic outcomes of enzyme replacement therapy for late-onset Fabry patients with the Chinese hotspot mutation (IVS4+919G>A)

    PubMed Central

    2014-01-01

    Background In Taiwan, DNA-based newborn screening showed a surprisingly high incidence (1/875 in males and 1/399 in females) of a cardiac Fabry mutation (IVS4 + 919G > A). However, the natural course, long-term treatment outcomes and suitable biomarkers for monitoring the therapeutic outcomes of these patients are largely unknown. Methods Fabry disease (FD) patients who had received enzyme replacement therapy (ERT) for more than 1 year were enrolled in this study from December 2008 to April 2013. Periodic echocardiography and serum globotriaosylsphingosine (lyso-Gb3) analysis were carried out. Before and after ERT, left ventricular mass index (LVMI) and serum lyso-Gb3 level were compared and the correlation between the change of LVMI and the change of serum lyso-Gb3 were also analyzed. Results Thirty-six patients, in four patient groups, were enrolled: (1) 16 males with IVS4 + 919G > A mutation; (2) 7 females with IVS4 + 919G > A mutation; (3) 2 males with classical mutations; and (4) 11 females with classical mutations. The follow-up period was 13–46 months. There were significant LVMI reductions after ERT in all four groups after excluding confounding factors. However, interestingly, serum lyso-Gb3 decreased significantly in the early period after ERT in all groups, but increased gradually after an average of 11.1 months after ERT in late-onset male and female Fabry groups, even when their LVMI still decreased or remained stable. Furthermore, there was no correlation between the change of serum lyso-Gb3 and the change of LVMI in both classical and IVS4 + 919G > A FD patients. Conclusion Although lyso-Gb3 has a high diagnostic sensitivity in late-onset Fabry patients and has a good response to ERT during the early stages, it might not be a reliable marker for monitoring the long-term therapeutic outcomes of ERT for late-onset Fabry patients with the Chinese hotspot mutation (IVS4 + 919G > A). PMID:25047006

  17. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease.

    PubMed

    Mignani, Renzo; Pieruzzi, Federico; Berri, Francesco; Burlina, Alessandro; Chinea, Benito; Gallieni, Maurizio; Pieroni, Maurizio; Salviati, Alessandro; Spada, Marco

    2016-10-01

    Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R (2) = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients.

  18. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease

    PubMed Central

    Mignani, Renzo; Pieruzzi, Federico; Berri, Francesco; Burlina, Alessandro; Chinea, Benito; Gallieni, Maurizio; Pieroni, Maurizio; Salviati, Alessandro; Spada, Marco

    2016-01-01

    Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R2 = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients. PMID:27679722

  19. The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

    PubMed Central

    Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P.; Viana-Baptista, Miguel; Gomes, António Caldeira; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C.; Oliveira, João Paulo

    2015-01-01

    Summary Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue – GLA p.(Arg118Cys) –, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands’ close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease, since the allelic frequency in stroke patients was 0.0087 (p=0.0185 vs the general population). The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for “rare” condition. PMID:25468652

  20. Enzyme replacement therapy in a patient of heterozygous Fabry disease: clinical and pathological evaluations by repeat kidney biopsy and a successful pregnancy.

    PubMed

    Iwafuchi, Yoichi; Maruyama, Hiroki; Morioka, Tetsuo; Noda, Seiko; Nagata, Hiroshi; Oyama, Yuko; Narita, Ichiei

    2017-10-10

    Fabry disease is a rare X-linked lysosomal storage disorder of glycosphingolipid catabolism caused by deficient activity of the lysosomal hydrolase alpha-galactosidase A (ɑ-Gal A). A 20-year-old woman was referred to our hospital because of proteinuria and persistent macroscopic hematuria. Based on the typical renal pathological findings, deficient activity of the ɑ-Gal A, and heterozygous mutation in the ɑ-Gal A gene, she was diagnosed with Fabry disease. After 1 year of enzyme replacement therapy with agalsidase alfa at 0.2 mg/kg every other week, the patient's proteinuria and hematuria were disappeared. In our patient, enzyme replacement therapy with agalsidase alfa was observed to be safe and well-tolerated during her pregnancy, with no significant negative effects on her or her child. Here, we report clinical and pathological evaluations of a patient through repeat kidney biopsy after 6 years of enzyme replacement therapy. Furthermore, we discussed the appropriate enzyme replacement therapy and its safety in pregnant women with Fabry disease.

  1. The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies.

    PubMed

    Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P; Viana-Baptista, Miguel; Caldeira-Gomes, António; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C; Oliveira, João Paulo

    2015-02-01

    Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Replacement of α-galactosidase A in Fabry disease: effect on fibroblast cultures compared with biopsied tissues of treated patients

    PubMed Central

    Keslová-Veselíková, Jana; Hůlková, Helena; Dobrovolný, Robert; Asfaw, Befekadu; Poupětová, Helena; Berná, Linda; Sikora, Jakub; Goláň, Lubor

    2008-01-01

    The function and intracellular delivery of enzyme therapeutics for Fabry disease were studied in cultured fibroblasts and in the biopsied tissues of two male patients to show diversity of affected cells in response to treatment. In the mutant fibroblasts cultures, the final cellular level of endocytosed recombinant α-galactosidases A (agalsidases, FabrazymeTM, and ReplagalTM) exceeded, by several fold, the amount in control fibroblasts and led to efficient direct intra-lysosomal hydrolysis of (3H)Gb3Cer. In contrast, in the samples from the heart and some other tissues biopsied after several months of enzyme replacement therapy (ERT) with FabrazymeTM, only the endothelial cells were free of storage. Persistent Gb3Cer storage was found in cardiocytes (accompanied by increase of lipopigment), smooth muscle cells, fibroblasts, sweat glands, and skeletal muscle. Immunohistochemistry of cardiocytes demonstrated, for the first time, the presence of a considerable amount of the active enzyme in intimate contact with the storage compartment. Factors responsible for the limited ERT effectiveness are discussed, namely post-mitotic status of storage cells preventing their replacement by enzyme supplied precursors, modification of the lysosomal system by longstanding storage, and possible relative lack of Sap B. These observations support the strategy of early treatment for prevention of lysosomal storage. PMID:18351385

  3. Renal complications of Fabry disease in children.

    PubMed

    Najafian, Behzad; Mauer, Michael; Hopkin, Robert J; Svarstad, Einar

    2013-05-01

    Fabry disease is an X-linked α-galactosidase A deficiency, resulting in accumulation of glycosphingolipids, especially globotriaosylceramide, in cells in different organs in the body. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. Recent studies support the value of renal biopsy in providing histological information relevant to kidney function and prognosis, and renal biopsy could potentially be used to guide treatment decisions in young Fabry patients. This review aims to provide an update of the current understanding, challenges, and needs to better approach renal complications of Fabry disease in children.

  4. Renal Complications of Fabry Disease in Children

    PubMed Central

    Najafian, Behzad; Mauer, Michael; Hopkin, Robert J; Svarstad, Einar

    2013-01-01

    Fabry disease is an X-linked α-galactosidase A deficiency, resulting in accumulation of glycosphingolipids, especially globotriaosylceramide, in cells in different organs in the body. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. Recent studies support the value of renal biopsy in providing histological information relevant to kidney function and prognosis and renal biopsy could potentially be used to guide treatment decisions in young Fabry patients. This review aims to provide an update of the current understanding, challenges and needs to better approach renal complications of Fabry disease in children. PMID:22898981

  5. Nano-LC-MS/MS for Quantification of Lyso-Gb3 and Its Analogues Reveals a Useful Biomarker for Fabry Disease.

    PubMed

    Sueoka, Hideaki; Ichihara, Junji; Tsukimura, Takahiro; Togawa, Tadayasu; Sakuraba, Hitoshi

    2015-01-01

    Biomarkers useful for diagnosis and evaluation of treatment for patients with Fabry disease are urgently needed. Recently, plasma globotriaosylsphingosine (lyso-Gb3) and lyso-Gb3-related analogues have attracted attention as promising biomarkers of Fabry disease. However, the plasma concentrations of lyso-Gb3 and its analogues are extremely low or below the detection limits in some Fabry patients as well as in healthy subjects. In this paper, we introduce the novel application of a nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) system to the measurement of lyso-Gb3 and its analogues in plasma. Nano-LC-MS/MS requires smaller amounts of samples and is more sensitive than conventional techniques. Using this method, we measured the plasma concentrations of lyso-Gb3 and its analogues in 40 healthy subjects, 5 functional variants (males with E66Q), and various Fabry patients (9 classic Fabry males/9 mutations; 7 later-onset Fabry males/5 mutations; and 10 Fabry females/9 mutations). The results revealed that the mean lyso-Gb3 and lyso-Gb3(-2) concentrations in all the Fabry patient subgroups were statistically higher, especially in the classic Fabry males, than those in the functional variants and healthy subjects. The plasma concentrations of lyso-Gb3 and its analogues in healthy subjects, functional variants, and some Fabry patients with specific mutations (R112H and M296I) that cannot be established by conventional techniques were successfully determined by means of nano-LC-MS/MS. The lyso-Gb3 and lyso-Gb3(-2) concentrations in male patients with these mutations were lower than those in most Fabry patients having other mutations, but higher than those in the functional variants and healthy subjects. This new method is expected to be useful for sensitive determination of the plasma concentrations of lyso-Gb3 and its analogues. This study also revealed that not only lyso-Gb3 but also lyso-Gb3(-2) in plasma is a useful biomarker for the diagnosis of

  6. Nano-LC-MS/MS for Quantification of Lyso-Gb3 and Its Analogues Reveals a Useful Biomarker for Fabry Disease

    PubMed Central

    Sueoka, Hideaki; Ichihara, Junji; Tsukimura, Takahiro; Togawa, Tadayasu; Sakuraba, Hitoshi

    2015-01-01

    Biomarkers useful for diagnosis and evaluation of treatment for patients with Fabry disease are urgently needed. Recently, plasma globotriaosylsphingosine (lyso-Gb3) and lyso-Gb3-related analogues have attracted attention as promising biomarkers of Fabry disease. However, the plasma concentrations of lyso-Gb3 and its analogues are extremely low or below the detection limits in some Fabry patients as well as in healthy subjects. In this paper, we introduce the novel application of a nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) system to the measurement of lyso-Gb3 and its analogues in plasma. Nano-LC-MS/MS requires smaller amounts of samples and is more sensitive than conventional techniques. Using this method, we measured the plasma concentrations of lyso-Gb3 and its analogues in 40 healthy subjects, 5 functional variants (males with E66Q), and various Fabry patients (9 classic Fabry males/9 mutations; 7 later-onset Fabry males/5 mutations; and 10 Fabry females/9 mutations). The results revealed that the mean lyso-Gb3 and lyso-Gb3(-2) concentrations in all the Fabry patient subgroups were statistically higher, especially in the classic Fabry males, than those in the functional variants and healthy subjects. The plasma concentrations of lyso-Gb3 and its analogues in healthy subjects, functional variants, and some Fabry patients with specific mutations (R112H and M296I) that cannot be established by conventional techniques were successfully determined by means of nano-LC-MS/MS. The lyso-Gb3 and lyso-Gb3(-2) concentrations in male patients with these mutations were lower than those in most Fabry patients having other mutations, but higher than those in the functional variants and healthy subjects. This new method is expected to be useful for sensitive determination of the plasma concentrations of lyso-Gb3 and its analogues. This study also revealed that not only lyso-Gb3 but also lyso-Gb3(-2) in plasma is a useful biomarker for the diagnosis of

  7. Genetics Home Reference: Fabry disease

    MedlinePlus

    ... Anderson-Fabry disease angiokeratoma corporis diffusum angiokeratoma diffuse ceramide trihexosidase deficiency Fabry's ... Lipid Metabolism Disorders Genetic and Rare Diseases Information Center ( ...

  8. Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults.

    PubMed

    Ortiz, Alberto; Oliveira, João P; Wanner, Christoph; Brenner, Barry M; Waldek, Stephen; Warnock, David G

    2008-06-01

    Progressive loss of kidney function complicates Fabry disease, an X-linked lysosomal storage disorder that arises from deficiency of alpha-galactosidase activity. Heterozygous females with Fabry disease can be as severely affected as hemizygous males, who have the classic form of the disease. Enzyme-replacement therapy with recombinant human alpha-galactosidase clears the glycosphingolipid globotriaosylceramide from kidney cells, and can stabilize renal function in adults with mild to moderate Fabry nephropathy. However, adults with more advanced nephropathy and overt proteinuria do not respond as well. For these patients, antiproteinuric therapy given in conjunction with enzyme-replacement therapy might prevent further decline in kidney function. In this Review, we propose guidelines and recommendations for the diagnosis and management of Fabry nephropathy in adults, based on published data and on the consensus of opinion of participants in the 7(th) International Fabry Nephropathy Roundtable in 2007. These organ-specific guidelines could be easier to implement than general guidelines, provided they are used in the context of an overall multisystem care approach.

  9. The Mutation p.D313Y is Associated with Organ Manifestation in Fabry Disease.

    PubMed

    du Moulin, M; Koehn, A F; Golsari, A; Dulz, S; Atiskova, Y; Patten, M; Münch, J; Avanesov, M; Ullrich, K; Muschol, N

    2017-03-09

    Fabry disease is a multisystem lysosomal storage disorder caused by mutations in the GLA gene. The clinical significance of the mutation p.D313Y is still under debate. Retrospective chart analysis of clinical (neurological, cardiac, renal, ophthalmological), genetic, and biochemical (lyso-globotriaosylsphingosine, lyso-Gb3; enzyme activity) data was done in all our patients carrying the p.D313Y mutation. Fourteen patients from 5 families (10 female, 4 male; age range 10-51) were included. Symptoms and organ manifestations compatible with Fabry disease could be identified in 10 patients. Cerebrovascular events occurred in 4 females. Seven patients reported pain or acroparaesthesia. Cornea verticillata was found in one patient, mild retinal vascular tortuosity in 5 patients. Lyso-Gb3 was elevated in 2 females with cerebrovascular involvement. Classical cardiac, renal or skin manifestations could not be identified. The mutation p.D313Y in the GLA gene may lead to organ manifestations and elevation of the Fabry-specific biomarker lyso-Gb3. Neurological symptoms (stroke and pain) and ocular manifestations seem to be the leading findings. Annual routine visits are recommended for patients carrying the p.D313Y mutation. Enzyme replacement therapy might be considered in symptomatic patients.

  10. Small fiber dysfunction predominates in Fabry neuropathy.

    PubMed

    Dütsch, M; Marthol, H; Stemper, B; Brys, M; Haendl, T; Hilz, M J

    2002-12-01

    Fabry disease is an X-linked recessive disease with a reduction of lysosomal alpha galactosidase A and consecutive storage of glycolipids e.g., in the brain, kidney, skin, and nerve fibers. Cardinal neurologic findings are hypohidrosis, painful episodes, and peripheral neuropathy. So far, the neurophysiological findings regarding the extent of large and small fiber dysfunction are contradictory. This study evaluated large and small nerve fiber function in a homogeneous group of Fabry patients. In 24 of 30 Fabry patients with creatinine below 194.7 mmol/L the authors assessed median, ulnar, and peroneal motor conduction velocity (MCV) and median, ulnar, and sural sensory conduction velocity (SCV) nerve conduction to study the function of thickly myelinated nerve fibers. In addition, the authors studied sympathetic skin responses (SSR) at both hands and feet in 24 patients. To evaluate A beta nerve fiber function, the authors determined vibratory detection thresholds (VDT) at the first toe in 30 patients. Function of A delta and C fibers was assessed by quantitative sensory testing of cold detection threshold (CDT) and heat-pain detection thresholds (HPDT). Nerve conduction studies showed significantly decreased amplitudes of MCVs and SCVs in Fabry patients as compared to controls. However, individual results of MCV and SCV studies were only mildly impaired. SSRs were present in all tested patients but SSR amplitudes were significantly decreased in Fabry patients in comparison to controls. VDT, CDT, and HPDT were significantly elevated in Fabry patients as compared to controls. However, only six patients had pathologic VDT, 19 had increased CDT, and 25 had elevated HPDT at a high level of stimulation. In Fabry patients, small fiber dysfunction is more prominent than large fiber dysfunction, confirming previous findings of sural nerve biopsies. The results suggest a higher vulnerability of small-diameter nerve fibers than of the thickly myelinated fibers.

  11. Blood pressure, proteinuria and nephropathy in Fabry disease.

    PubMed

    Jain, Gaurav; Warnock, David G

    2011-01-01

    Fabry disease is an X-linked disorder leading to abnormal accumulation of glycosphingolipids with multisystem involvement, including cardiac, renal, dermatologic and neurologic manifestations. Fabry nephropathy, specifically proteinuria and progressive chronic kidney disease, have taken center stage over the past decade, defining disease outcomes as well as mortality associated with Fabry disease. Systemic blood pressure among patients with Fabry disease is relatively low, compared to other forms of proteinuric chronic kidney disease. This review is based on a systematic survey of recent publications that describe the diagnosis and treatment of Fabry nephropathy in adults. A high percentage of patients with Fabry disease have been shown to have proteinuria, and a small but significant percentage of Fabry patients have overt hypertension. Recent efforts have focused on the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEIs/ARBs) in addition to enzyme replacement therapy (ERT) for treatment of Fabry nephropathy. The proven beneficial effects of ACEI/ARBs for more common forms of proteinuric kidney disease have been extrapolated to the treatment of Fabry nephropathy. The overall treatment goal with ACEIs/ARBs, in combination with ERT, is reduction of urinary protein excretion to less than 500 mg/day, and stabilization of the decline of kidney function to -1 ml/min/1.73 m(2)/year. ERT alone, in the absence of ACEIs/ARBs does not decrease proteinuria in Fabry patients. We present the prevalence of proteinuria, kidney disease and hypertension in Fabry disease and discuss treatment goals for the treatment of this unusual form of proteinuric kidney disease. There are some practical challenges to the use of standard antiproteinuric therapy in Fabry disease that need to be addressed to optimize patient outcome, with the expectation that kidney function can be preserved with the combination of ERT and ACEI/ARB therapy. Copyright © 2010 S

  12. Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry Disease.

    PubMed

    Azevedo, Olga; Gago, Miguel; Miltenberger-Miltenyi, Gabriel; Gaspar, Paulo; Sousa, Nuno; Cunha, Damião

    2017-02-03

    We report on the clinical, biochemical, and genetic findings of a large family with the classical phenotype of Fabry disease due to the novel nonsense mutation c.607G>T (p.E203X) of the GLA gene, which occurs in the active site of the α-galactosidase A enzyme. This report highlights that (i) Fabry disease diagnosis should be considered in all cases of unexplained left ventricular hypertrophy (LVH), even in its milder forms; (ii) a complete evaluation of patients with unexplained LVH is important to find diagnostic red flags of treatable causes of LVH, such as Fabry disease; (iii) cascade family screening is paramount to the earlier diagnosis and treatment of other affected family members; and (iv) the Fabry disease phenotype is highly variable in heterozygote females, even within the same family.

  13. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease.

    PubMed

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11-12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11-12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11-12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease.

  14. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease

    PubMed Central

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11–12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11–12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11–12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  15. Ear symptoms in children with Fabry disease: data from the Fabry Outcome Survey.

    PubMed

    Keilmann, A; Hajioff, D; Ramaswami, U

    2009-12-01

    Hearing loss and tinnitus are common symptoms in Fabry disease and increase in prevalence with age. This study aimed to provide an epidemiological description of hearing impairment and tinnitus in children with Fabry disease in the Fabry Outcome Survey (FOS), an international database to assess the natural history of Fabry disease and the efficacy of enzyme replacement therapy with agalsidase alpha. Signs and symptoms questionnaires were completed for 543 children with Fabry disease. Pure-tone audiograms were obtained from 101 children (53 girls, 48 boys). On questioning, 33% of the children (n = 179) reported subjective hearing impairment. However, when assessed by age-appropriate audiometry, only 19 of 101 patients (19%) had a persistent hearing loss at least one frequency. Of these, 14 had a high-frequency hearing loss, 4 a pan-frequency hearing loss, and 1 a pattern typical of noise-induced loss. Of the 101 children with audiometry, 44 complained of tinnitus. Only 2 children reported sudden hearing loss, which was not verified by audiometry. Children with tinnitus had greater disease severity scores. Hearing loss is a well-known clinical manifestation in patients with Fabry disease. It was reported in significant numbers of children in the FOS signs and symptoms questionnaire, but confirmed in only 19% by formal audiometry. The subjective hearing impairment may have been due to middle-ear effusions in many cases. Tinnitus is a well-recognized symptom in Fabry disease and can present in childhood. The presence of tinnitus correlated with overall disease severity.

  16. Fabry's Disease: Case Series and Review of Literature

    PubMed Central

    Wani, Muzaffar Maqsood; Khan, Imran; Bhat, Riyaz Ahmad; Ahmad, Muzaffar

    2016-01-01

    Fabry's disease is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme with the progressive accumulation of globotriaosylceramide in vascular endothelial cells leading to cardiovascular, renal, gastrointestinal, neuropathic, lenticular, and dermatological manifestations. It is a rare cause of end-stage renal disease. It classically affects males whereas 10–15% of female heterozygote carriers are affected depending on localization. Both the FD and its association with ESRD is rare. With this background, this case series of five patient's along with the review of literature is presented here. PMID:27398254

  17. Malignant syphilis in an immunocompetent female patient*

    PubMed Central

    Requena, Camila Bueno; Orasmo, Cínthia Rosane; Ocanha, Juliana Polizel; Barraviera, Silvia Regina Catharino Sartore; Marques, Mariangela Esther Alencar; Marques, Silvio Alencar

    2014-01-01

    Malignant syphilis is an uncommon manifestation of secondary syphilis, in which necrotic lesions may be associated with systemic signs and symptoms. Generally it occurs in an immunosuppressed patient, mainly HIV-infected, but might be observed on those who have normal immune response. Since there is an exponential increase in the number of syphilis cases, more diagnoses of malignant syphilis must be expected. We report a case in an immunocompetent female patient. PMID:25387504

  18. Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase

    PubMed Central

    Warnock, David G.; Bichet, Daniel G.; Holida, Myrl; Goker-Alpan, Ozlem; Nicholls, Kathy; Thomas, Mark; Eyskens, Francois; Shankar, Suma; Adera, Mathews; Sitaraman, Sheela; Khanna, Richie; Flanagan, John J.; Wustman, Brandon A.; Barth, Jay; Barlow, Carrolee; Valenzano, Kenneth J.; Lockhart, David J.; Boudes, Pol; Johnson, Franklin K.

    2015-01-01

    Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT) with either agalsidase alfa (Replagal) or agalsidase beta (Fabrazyme). Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified. Trial Registration ClinicalTrials.gov NCT01196871 PMID:26252393

  19. Fabry disease and incidence of cancer.

    PubMed

    Bird, Sarah; Hadjimichael, Efthymios; Mehta, Atul; Ramaswami, Uma; Hughes, Derralynn

    2017-09-06

    Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of α-galactosidase A and the resulting accumulation of the glycosphingolipid globotriaosylceramide (Gb3) and its derivatives, including globotriaosylsphingosine (Lyso-Gb3). Increased cellular and plasma levels of Gb3 and Lyso-Gb3 affect multiple organs, with specific clinical consequences for the kidneys, heart and brain. There is growing evidence that alterations in glycosphingolipids may have an oncogenic role and this prompted a review of cases of cancer and benign lesions in a large single centre cohort of Fabry patients. We also explored whether there is a difference in the risk of cancer in Fabry patients compared to the general population. Our results suggest that Fabry patients may have a marginally reduced rate of all cancer (incidence rate ratio 0.61, 95% confidence interval 0.37 to 0.99) but possibly increased rates of melanoma, urological malignancies and meningiomas. Greater knowledge and awareness of cancer in patients with Fabry disease may help identify at-risk individuals and elucidate cancer mechanisms in this rare inherited disease, which may potentially be relevant to the wider cancer population.

  20. Psychological Counseling of Female Fertility Preservation Patients

    PubMed Central

    Lawson, Angela K.; Klock, Susan C.; Pavone, Mary Ellen; Hirshfeld-Cytron, Jennifer; Smith, Kristin N.; Kazer, Ralph R.

    2015-01-01

    Young cancer patients are increasingly interested in preserving their fertility prior to undergoing gonadotoxic therapies. Although the medical safety and treatment protocols for fertility preservation have been well documented, limited research has addressed the emotional issues which arise in fertility preservation patients. We briefly review the literature on the psychosocial issues in adult female fertility preservation treatment and describe our experiences within this patient population patient. Our findings suggest that several important issues to be addressed during the psychological counseling of adult female fertility preservation patients include: 1) pre-existing psychological distress in patients undergoing treatment, 2) choice of fertility preservation strategy in the face of an uncertain relationship future, 3) decision making regarding use of third party reproduction (e.g., sperm/egg donation, gestational surrogacy), 4) treatment expectations regarding pregnancy and miscarriage, 5) ethical issues related to treatment including the creation, cryopreservation, and disposition of embryos/oocytes, and 6) decision regret from patients who declined fertility preservation. PMID:25996581

  1. Dialysis and transplantation in Fabry disease: indications for enzyme replacement therapy.

    PubMed

    Mignani, Renzo; Feriozzi, Sandro; Schaefer, Roland M; Breunig, Frank; Oliveira, João Paulo; Ruggenenti, Piero; Sunder-Plassmann, Gere

    2010-02-01

    ESRD is a major cause of morbidity and premature mortality in Fabry disease, particularly in classically affected males. The decline of renal function in Fabry nephropathy is adversely affected by male gender, advanced chronic kidney disease (CKD), and severe proteinuria. The diagnosis of Fabry nephropathy may be missed if not specifically addressed in progressive CKD and patients have been first identified in screening programs of dialysis patients. Fabry patients have worse 3-year survival rates on dialysis as compared with nondiabetic controls. The 5-year survival rate of transplanted Fabry patients is also lower than that of controls. However, because Fabry nephropathy does not recur in the allograft and transplanted Fabry patients appear to have better overall outcomes than those maintained on dialysis, kidney transplantation should be recommended as a first choice in renal replacement therapy (RRT) for Fabry disease. Appropriately designed and powered studies are not available to answer the question whether enzyme replacement therapy (ERT) influences outcomes, the course of cardiomyopathy, events, or survival in Fabry patients on RRT. The authors are not aware of compelling indications for ERT in RRT patients because progression of cardiomyopathy was documented during ERT. Whether the excess mortality risk of Fabry patients on RRT can be prevented by ERT is unknown. Despite observational reports of symptomatic improvement, the available evidence supporting ERT for such patients is not compelling enough. To clarify this issue, studies are needed to test the effectiveness of agalsidases in preventing cardiac and cerebrovascular complications in Fabry patients with ESRD.

  2. Gender Differences in the Application of Spanish Criteria for Initiation of Enzyme Replacement Therapy for Fabry Disease in the Fabry Outcome Survey.

    PubMed

    Barba-Romero, Miguel-Ángel; Pintos-Morell, Guillem

    2016-11-24

    Both male/female patients with Fabry disease (FD) may receive enzyme replacement therapy (ERT). Previously published analyses of the Fabry Outcome Survey (FOS; Shire-sponsored) database suggested gender differences in timing of ERT initiation. We assessed alignment of criteria for ERT initiation in the Spanish adult population included in FOS with recommendations of a Spanish national consensus. This retrospective analysis examined baseline clinical data of 88 adults (49 females) enrolled in the FOS database up to August 2014. Thirty-five (39.8%) patients were not receiving ERT: five (12.8%) males and 30 (61.2%) females. Baseline disease severity on the FOS-derived Mainz Severity Score Index was lower in untreated males (median (interquartile range), 0.0 (0.0-1.0)) than treated males (TM; 15.0 (7.5-26.5)), and was similar in untreated and treated females. The percentage of untreated females with at least one criterion for treatment initiation was 76.7% versus 100.0% of treated females (p = 0.0340) and 97.1% (p = 0.0210) of TM. In discordance with Spanish consensus recommendations, a substantial number of females with evidence of FD who might benefit from ERT have not yet initiated treatment. These results suggest unequal gender perceptions with respect to ERT initiation in Spain.

  3. Gender Differences in the Application of Spanish Criteria for Initiation of Enzyme Replacement Therapy for Fabry Disease in the Fabry Outcome Survey

    PubMed Central

    Barba-Romero, Miguel-Ángel; Pintos-Morell, Guillem

    2016-01-01

    Both male/female patients with Fabry disease (FD) may receive enzyme replacement therapy (ERT). Previously published analyses of the Fabry Outcome Survey (FOS; Shire-sponsored) database suggested gender differences in timing of ERT initiation. We assessed alignment of criteria for ERT initiation in the Spanish adult population included in FOS with recommendations of a Spanish national consensus. This retrospective analysis examined baseline clinical data of 88 adults (49 females) enrolled in the FOS database up to August 2014. Thirty-five (39.8%) patients were not receiving ERT: five (12.8%) males and 30 (61.2%) females. Baseline disease severity on the FOS-derived Mainz Severity Score Index was lower in untreated males (median (interquartile range), 0.0 (0.0–1.0)) than treated males (TM; 15.0 (7.5–26.5)), and was similar in untreated and treated females. The percentage of untreated females with at least one criterion for treatment initiation was 76.7% versus 100.0% of treated females (p = 0.0340) and 97.1% (p = 0.0210) of TM. In discordance with Spanish consensus recommendations, a substantial number of females with evidence of FD who might benefit from ERT have not yet initiated treatment. These results suggest unequal gender perceptions with respect to ERT initiation in Spain. PMID:27886142

  4. Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients

    PubMed Central

    Gonçalves, Maria J.; Mourão, Ana F.; Martinho, António; Simões, Olívia; Melo-Gomes, José; Salgado, Manuel; Estanqueiro, Paula; Ribeiro, Célia; Brito, Iva; Fonseca, João E.; Canhão, Helena

    2017-01-01

    Fabry’s disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No “classic” pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292). PMID:28299312

  5. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis.

    PubMed

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-06-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m(2) had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m(2)/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m(2.7)/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take

  6. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis

    PubMed Central

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-01-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m2 had a mean (standard error of the mean [SEM]) annualized change in eGFR of − 2.86 (0.53) mL/min/1.73 m2/y compared with − 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m2.7/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into

  7. Delayed diagnosis of Fabry disease presenting as myocardial ischaemia.

    PubMed

    Marcì, Marcello; Duro, Giovanni; Tuttolomondo, Antonino; Tuttolomondo, Bruno; Pinto, Antonio; Cirrincione, Vincenzo; Sanfilippo, Nicola

    2012-01-01

    Cardiovascular complications due to the accumulation of globotriaosylceramide in cardiac cells occur in almost all patients affected by Anderson-Fabry disease. Cardiac manifestations include left ventricular hypertrophy, mitral regurgitation, conduction disturbances and myocardial ischaemia. We report a case of Fabry's disease diagnosed several years after the onset of early cardiac symptoms.

  8. Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

    PubMed Central

    Wijburg, Frits A.; Bénichou, Bernard; Bichet, Daniel G.; Clarke, Lorne A.; Dostalova, Gabriela; Fainboim, Alejandro; Fellgiebel, Andreas; Forcelini, Cassiano; An Haack, Kristina; Hopkin, Robert J.; Mauer, Michael; Najafian, Behzad; Scott, C. Ronald; Shankar, Suma P.; Thurberg, Beth L.; Tøndel, Camilla; Tylki-Szymańska, Anna; Ramaswami, Uma

    2015-01-01

    Trial Design This analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial. Methods Males aged 5–18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13–17 years), renal function, and glycolipid levels (plasma, urine). Results Plasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m2 (range 90.4–161.0 mL/min/1.73 m2) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0–27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients. Conclusions These data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of

  9. Immunohistochemical diagnosis of Fabry nephropathy and localisation of globotriaosylceramide deposits in paraffin-embedded kidney tissue sections.

    PubMed

    Valbuena, Carmen; Leitão, Dina; Carneiro, Fátima; Oliveira, João Paulo

    2012-02-01

    Fabry disease (FD) is a rare X-linked lysosomal storage disorder of glycosphingolipids, mostly globotriaosylceramide (Gb3). Proteinuric chronic kidney disease develops frequently, and recognition of Fabry nephropathy on a kidney biopsy may be the first clue to the underlying diagnosis. Since the accumulated glycosphingolipids are largely extracted by the paraffin-embedding procedure, the most characteristic feature of Fabry nephropathy on routine light microscopy (LM) is nonspecific cell vacuolization. To test whether residual Gb3 in kidney tissue might be exploited for the specific diagnosis of Fabry nephropathy, paraffin-embedded kidney biopsies of nine FD patients (one boy, four men, four women) and of a female carrier of a mild genetic mutation, with no evidence of Fabry nephropathy, were immunostained with an anti-Gb3 antibody. The adult biopsies were additionally co-stained with a lysosomal marker (anti-lysosomal-associated membrane protein 2 (anti-LAMP2) antibody). The distribution of Gb3 deposits was scored per cell type and compared to the histological scorings of glycosphingolipid inclusions on semi-thin sections. FD patients had residual Gb3 in all types of glomerular, tubular, interstitial and vascular kidney cells. The highest expression of LAMP2 was seen in tubular cells, but there were no meaningful associations between LAMP2 expression and prevalence of Gb3 deposits on different kidney cell types. The histological scorings of glycosphingolipid inclusions were relatively higher than the corresponding immunohistochemical scorings of Gb3 deposits. In the mildly affected female, Gb3 expression was limited to tubular cells, a pattern similar to controls. Gb3 immunostaining allows the specific diagnosis of Fabry nephropathy even in kidney biopsies routinely processed for LM.

  10. Fabry nephropathy: indications for screening and guidance for diagnosis and treatment by the European Renal Best Practice.

    PubMed

    Terryn, Wim; Cochat, Pierre; Froissart, Roseline; Ortiz, Alberto; Pirson, Yves; Poppe, Bruce; Serra, Andreas; Van Biesen, Wim; Vanholder, Raymond; Wanner, Christoph

    2013-03-01

    Fabry disease (FD) is an X-linked disorder of glycosphingolipid catabolism resulting in the accumulation of glycolipids including globotriaosylceramide in cells of various tissues resulting in end-organ manifestations. Initially, FD is typically characterized by angiokeratoma and recurrent episodes of neuropathic pain in the extremities occurring during childhood or adolescence. Most affected patients also exhibit a decreased ability to sweat. Later in life, FD results in left ventricular hypertrophy, proteinuria, renal failure and stroke. These later disease manifestations are non-specific and also common in diabetes, hypertension and atheromatosis and thus for most practitioners do not point into the direction of FD. As a consequence, FD is under-diagnosed and screening of high-risk groups is important for case finding, as is a thorough pedigree analysis of affected patients. In the nephrology clinic, we suggest to screen patients for FD when there is unexplained chronic kidney disease in males younger than 50 years and females of any age. In men, this can be performed by measuring α-galactosidase A activity in plasma, white blood cells or dried blood spots. In women, mutation analysis is necessary, as enzyme measurement alone could miss over one-third of female Fabry patients. A multidisciplinary team should closely monitor all known Fabry patients, with the nephrologist screening kidney impairment (glomerular filtration rate and proteinuria) on a regular basis. Transplanted Fabry patients have a higher mortality than the regular transplant population, but have acceptable outcomes, compared with Fabry patients remaining on dialysis. It is unclear whether enzyme replacement therapy (ERT) prevents deterioration of kidney function. In view of the lack of compelling evidence for ERT, and the low likelihood that a sufficiently powered randomized controlled trial on this topic will be performed, data of all patients with FD should be collected in a central registry.

  11. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina.

    PubMed

    Kisinovsky, Isaac; Cáceres, Guillermo; Coronel, Cristina; Reisin, Ricardo

    2013-01-01

    Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme a-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years) and 36 females (mean age: 34 years). A total of 5229 infusions (mean: 59 per patient; range: 1-150) were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions). All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.

  12. Urethral hemangioma in a prepubertal female patient

    PubMed Central

    Li, Chiao-Ching; Li, Chiao-Zhu; Yen, Ching-Heng; Tsai, Wen-Chuan; Wu, Sheng-Tang; Cha, Tai-Lung; Meng, En

    2017-01-01

    Abstract Rationale: Urethral hemangiomas commonly occur in men or elderly women. We presented a rare case of urethral hemangioma in a prepubertal female patient. Patients concerns: An 8-year-old girl had the complaints of bloody staining of clothing, a foul perineal odor, and urethral pain. She was brought to our genitourinary outpatient department for survey and a single, 1-cm compressible reddish nodule at the 10-2 o’clock position in the distal urethra was found. Diagnoses: Urethral hemangioma in a prepubertal girl was diagnosed after excision of the urethral nodule. Interventions: Excision with 8 “stay” sutures in the protruding urethral mucosa was performed. Outcomes: Normal micturition without symptom recurrence was noted at the 3-month follow-up. Lessons: Urethral hemangioma is also found in prepubertal female patient. Increased physician awareness and early recognition of a urethral hemangioma can avoid unnecessary examinations and patient anxiety. The procedure of excision with 8 “stay” sutures in the protruding urethral mucosa facilitates mobilization from the distal urethra and provides a good surgical view of abnormal proliferative blood vessels. Therefore, the lesion can be removed as clean as possible. PMID:28353601

  13. [Fabry disease: clinic and enzymatic diagnosis of homozygous and heterozygous. New therapeutic prospects].

    PubMed

    Peces, R; Olea, T

    2002-01-01

    Fabry disease is an X-linked recessive lysosomal storage disorder caused by a partial or complete deficiency of alpha-galactosidase A. Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and early death. Men are predominantly affected but many female carriers have similar clinical involvement, including increased risk of stroke. Physical stigmata, such as angiokeratomas in skin and mucous membranes and characteristic benign corneal abnormalities, facilitate identification of Fabry disease. The finding of a marked decreased activity of (alpha-galactosidase A in plasma, white blood cells or cultured skin fibroblasts confirms the diagnosis. Treatment thus far has been symptomatic only. Etiology-based therapies are being developed that include enzyme replacement therapy, gene therapy, and substrate deprivation. The recently completed double-blind, placebo-controlled trials of intravenous infusions of (alpha-galactosidase A in patients with Fabry disease demonstrated the safety and efficacy of this treatment. We report a family with Fabry disease composed of hemicygous and heterocygous. The propositus developed chronic renal failure and received a cadaver renal transplant, which remained with adequate renal function during 15 years.

  14. Managing the Female Patient with Hereditary Angioedema

    PubMed Central

    Banerji, Aleena; Riedl, Marc

    2016-01-01

    Hereditary angioedema (HAE) is a rare disorder resulting from decreased functional levels of C1 -inhibitor (C1-INH), which manifests as periodic episodes of localized edema which can be extremely painful, debilitating and even fatal if the swelling affects the larynx. HAE can complicate many aspects of obstetric/gynecologic care, and an awareness of the disease is critical for clinicians involved in the care of women because of potential HAE-related complications pertaining to pregnancy, labor and delivery, and other women's health issues. This article provides a review of published literature specific to HAE and its management in female patients, including important concerns regarding obstetric/gynecologic care. A growing body of relevant experience is presented to help guide the care of women with HAE. PMID:26978558

  15. Managing the female patient with hereditary angioedema.

    PubMed

    Banerji, Aleena; Riedl, Marc

    2016-06-01

    Hereditary angioedema (HAE) is a rare disorder resulting from decreased functional levels of C1-inhibitor (C1-INH), which manifests as periodic episodes of localized edema which can be extremely painful, debilitating and even fatal if the swelling affects the larynx. HAE can complicate many aspects of obstetric/gynecologic care, and an awareness of the disease is critical for clinicians involved in the care of women because of potential HAE-related complications pertaining to pregnancy, labor and delivery, and other women's health issues. This article provides a review of published literature specific to HAE and its management in female patients, including important concerns regarding obstetric/gynecologic care. A growing body of relevant experience is presented to help guide the care of women with HAE.

  16. Fertility preservation in female classic galactosemia patients

    PubMed Central

    2013-01-01

    Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI) as a diet-independent complication of the disease. This is a major concern for patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group. The unique pathophysiology of classic galactosemia with a severely reduced follicle pool at an early age requires an adjusted approach. In this article recommendations for physicians based on current knowledge concerning galactosemia and fertility preservation are made. Fertility preservation is only likely to be successful in very young prepubertal patients. In this group, cryopreservation of ovarian tissue is currently the only available technique. However, this technique is not ready for clinical application, it is considered experimental and reduces the ovarian reserve. Fertility preservation at an early age also raises ethical questions that should be taken into account. In addition, spontaneous conception despite POI is well described in classic galactosemia. The uncertainty surrounding fertility preservation and the significant chance of spontaneous pregnancy warrant counseling towards conservative application of these techniques. We propose that fertility preservation should only be offered with appropriate institutional research ethics approval to classic galactosemia girls at a young prepubertal age. PMID:23866841

  17. Fertility preservation in female classic galactosemia patients.

    PubMed

    van Erven, Britt; Gubbels, Cynthia S; van Golde, Ron J; Dunselman, Gerard A; Derhaag, Josien G; de Wert, Guido; Geraedts, Joep P; Bosch, Annet M; Treacy, Eileen P; Welt, Corrine K; Berry, Gerard T; Rubio-Gozalbo, M Estela

    2013-07-16

    Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI) as a diet-independent complication of the disease. This is a major concern for patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group. The unique pathophysiology of classic galactosemia with a severely reduced follicle pool at an early age requires an adjusted approach. In this article recommendations for physicians based on current knowledge concerning galactosemia and fertility preservation are made. Fertility preservation is only likely to be successful in very young prepubertal patients. In this group, cryopreservation of ovarian tissue is currently the only available technique. However, this technique is not ready for clinical application, it is considered experimental and reduces the ovarian reserve. Fertility preservation at an early age also raises ethical questions that should be taken into account. In addition, spontaneous conception despite POI is well described in classic galactosemia. The uncertainty surrounding fertility preservation and the significant chance of spontaneous pregnancy warrant counseling towards conservative application of these techniques. We propose that fertility preservation should only be offered with appropriate institutional research ethics approval to classic galactosemia girls at a young prepubertal age.

  18. Anderson-Fabry disease in children.

    PubMed

    Sestito, Simona; Ceravolo, Ferdinando; Concolino, Daniela

    2013-01-01

    Although clinical evidence of major organ damage is typical of adulthood, many of the signs and symptoms of Anderson Fabry Disease (AFD) occur frequently in childhood. The clinical phenotype of AFD in pediatric patients has been described in several studies which show a higher incidence and an earlier onset of symptoms in male patients than in females. These include neurological manifestations (acroparaesthesias, chronic neuropathic pain, hypo-anhidrosis, tinnitus, hearing, loss), gastrointestinal (GI) symptoms (abdominal pain and diarrhea), angiokeratomas, ocular abnormalities (cornea verticillata, tortuous retinal vessels and subcapsular cataracts). Such manifestations may impair quality of life and, because of their unspecific nature, rarely lead to an early diagnosis. In addition, signs of major organ damage (microalbuminuria or proteinuria, urinary hyperfiltration, impaired heart rate variability, left ventricular hypertrophy, stroke) are encountered in children with AFD. Clinical trials of enzyme replacement therapy (ERT) with agalsidase alfa and agalsidase beta have been conducted in children, with clinical and pharmacodinamc effects proved by both enzyme formulations, whereas differences in safety profile and administration were found. Although several studies suggest that ERT should be started before irreversible damage in critical organs have occurred, the issue of when to initiate it has not yet been resolved. More controlled trials must be done in order to demonstrate that an early start of ERT could prevent adult complications and to assess the optimal timing of treatment in children with AFD. This review aims to provide an update of the current understanding for a better approach of pediatric AFD.

  19. Twenty novel mutations in the alpha-galactosidase A gene causing Fabry disease.

    PubMed Central

    Topaloglu, A. K.; Ashley, G. A.; Tong, B.; Shabbeer, J.; Astrin, K. H.; Eng, C. M.; Desnick, R. J.

    1999-01-01

    BACKGROUND: Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from the deficient activity of the lysosomal exoglycohydrolase alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A). The nature of the molecular lesions in the alpha-Gal A gene in 30 unrelated families was determined to provide precise heterozygote detection, prenatal diagnosis, and define genotype-phenotype correlations. MATERIALS AND METHODS: Genomic DNA was isolated from affected males and/or carrier females from 30 unrelated families with Fabry disease. The entire alpha-Gal A coding region and flanking intronic sequences were analyzed by PCR amplification and automated sequencing. RESULTS: Twenty new mutations were identified, each in a single family: C142R, G183D, S235C, W236L, D244H, P259L, M267I, I289F, Q321E, C378Y, C52X, W277X, IVS4(+4), IVS6(+2), IVS6(-1), 35del13, 256del1, 892ins1, 1176del4, and 1188del1. In the remaining 10 unrelated Fabry families, 9 previously reported mutations were detected: M42V, R112C, S148R, D165V, N215S (in 2 families), Q99X, C142X, R227X, and 1072del3. Haplotype analysis using markers closely flanking the alpha-Gal A gene indicated that the two patients with the N215S lesion were unrelated. The IVS4(+4) mutation was a rare intronic splice site mutation that causes Fabry disease. CONCLUSIONS: These studies further define the heterogeneity of mutations in the alpha-Gal A gene causing Fabry disease, permit precise heterozygote detection and prenatal diagnosis, and help delineate phenotype-genotype correlations in this disease.

  20. COMPUTER ASSISTED RETINAL VESSEL TORTUOSITY EVALUATION IN NOVEL MUTATION FABRY DISEASE: Towards New Prognostic Markers.

    PubMed

    San Román, Irene; Rodríguez, María-Elena; Caporossi, Orsola; Zoppetti, Claudia; Sodi, Andrea; Mecocci, Alessandro; López, David; Rodríguez, Beatriz; Gimeno, Juan-Ramón

    2017-03-01

    Fabry disease is a rare lysosomal storage disorder with systemic involvement. The authors report on a large Fabry family with GLA p.M187R mutation and exhaustive ophthalmologic assessment. Comprehensive systemic evaluation and genetic diagnosis were performed. Ophthalmologic evaluation included intraocular pressure/visual acuity measurement, refractometry, slit lamp examination, retinography, and optical coherence tomography. Three parameters quantified retinal vessel tortuosity: sum of angle metrics, product of angle distance, and triangular index. Calculations were semiautomatized using dedicated software. Ten individuals (2 males and 8 females) were described. Seventy-five percent had retinal vessel tortuosity. One hundred percent had cornea verticillata. Perimacular vessels were predominantly involved. The correlation between the right and left eye tortuosity measurements was very tight. A significant correlation between retinal vessel tortuosity and systemic severity measured by general Mainz Severity Score Index (MSSI), renal MSSI, and neurological MSSI but no cardiac MSSI was observed. Right sum of angle metrics value was an independent statistical predictor of the general-MSSI score in presence of age. p.M187R mutation causes a severe systemic and ophthalmologic phenotype, in both male and female patients. Semiautomatic assessment of retinal vessel tortuosity is an objective and reproducible tool. All three parameters of tortuosity are closely associated with Fabry severity scores. Studies of larger series are being awaited to establish the role of retinal vessel tortuosity as a noninvasive marker of disease progression.

  1. Bedside Stereomicroscopy of Fabry Kidney Biopsies: An Easily Available Method for Diagnosis and Assessment of Sphingolipid Deposits.

    PubMed

    Svarstad, Einar; Leh, Sabine; Skrunes, Rannveig; Kampevold Larsen, Kristin; Eikrem, Øystein; Tøndel, Camilla

    2017-08-26

    A previous case report found stereomicroscopic changes typical for Fabry disease in a kidney biopsy. This case series evaluates an expanded diagnostic capacity of the method. Bedside stereomicroscopy was performed in a cross-sectional prospective study of 31 consecutive enzyme-treated or treatment-naïve male (n = 14) and female Fabry disease patients. The burden of glomerular storage material was scored semiquantitatively on a visual analog scale (range 0-3) and a blinded comparison was done with a reference histologic method. Significant correlations (p < 0.001) were found between the stereomicroscopic scoring of glomerular characteristic white storage material and the amount of podocyte globotriaosylceramide (Gb3) deposits scored by standardized light microscopy. The bedside method correctly identified the variability of podocyte Gb3 accumulation after 10 years of identical agalsidase therapy in 2 brothers aged 24 and 27 years, and also identified tubular cell deposits. Stereomicroscopy correctly verified the absence of sphingolipid deposits in the biopsy of a female index patient with a genetic variant of unknown significance, and the diagnosis of Fabry disease was finally discarded. Bedside stereomicroscopy of kidney biopsies is an easily available, low-cost microscopy method handled by the clinician. The method carries a high diagnostic sensitivity for Fabry disease, reducing the risk of misdiagnosis in previously unknown cases. An expanded yield of the method is suggested, including the grading of the podocyte Gb3 burden and assessment of effectiveness of enzyme replacement therapy. We recommend the method as complementary to current standard histologic evaluation of Fabry kidney biopsies. © 2017 S. Karger AG, Basel.

  2. eNOS gene Glu298Asp and 4b/a polymorphisms are associated with renal function parameters in Mexican patients with Fabry disease.

    PubMed

    Marin-Medina, A; Brambila-Tapia, A J L; Picos-Cárdenas, V J; Gallegos-Arreola, M P; Figuera, L E

    2016-10-24

    Fabry disease (FD) is an inherited X-linked lysosomal disease that causes renal failure in a high percentage of affected individuals. The eNOS gene encodes for endothelial nitric oxide synthase, which plays an important role in glomerular hemodynamics. This gene has two main polymorphisms (Glu298Asp and 4b/a) that have been studied in the context of many different diseases, including those involving cardiovascular and renal alterations. Considering the lack of information regarding eNOS variants and FD, we investigated whether there were associations between eNOS genetic variants and renal function parameters in Mexican patients with FD and renal impairment. In total, 15 FD patients with renal alterations were included in the present study, and associations between eNOS polymorphisms and renal function parameters (urea, creatinine, and GFR) were evaluated. The Asp298 and 4a alleles of the eNOS gene were found to be significantly associated with increased levels of urea and creatinine, and a decreased glomerular filtration rate in FD patients, and this association behaved in a co-dominant fashion. Our results coincide with previous reports showing an association between these polymorphisms and kidney disease, and along with other studies regarding their role in the nitric oxide pathway, suggest that these variants affect the severity of nephropathy in patients with FD.

  3. Fabry disease: Evidence for a regional founder effect of the GLA gene mutation 30delG in Brazilian patients.

    PubMed

    de Alencar, Dayse Oliveira; Netto, Cristina; Ashton-Prolla, Patricia; Giugliani, Roberto; Ribeiro-Dos-Santos, Ândrea; Pereira, Fernanda; Matte, Ursula; Santos, Ney; Santos, Sidney

    2014-01-01

    The Fabry disease is caused by mutations in the gene (GLA) that encodes the enzyme α-galactosidase A (α-Gal A). More than 500 pathologic variants of GLA have already been described, most of them are family-specific. In southern Brazil, a frequent single-base deletion (GLA 30delG) was identified among four families that do not recognize any common ancestral. In order to investigate the history of this mutation (investigate the founder effect, estimate the mutation age and the most likely source), six gene-flanking microsatellite markers of the X chromosome on the mutation carriers and their parents, 150 individuals from the same population and 300 individuals that compose the Brazilian parental populations (Europeans, Africans and Native Americans) were genotyped. A common haplotype to the four families was identified and characterized as founder. The age was estimated with two statistics software (DMLE 2.2 and ESTIAGE) that agreed with 11 to 12 generations old. This result indicates that the mutation GLA 30delG was originated from a single event on the X chromosome of a European immigrant, during the southern Brazil colonization between 1710 and 1740.

  4. Choroidoretinal granuloma in a young female patient.

    PubMed

    Massa, Horace F; Gatzioufas, Zisis; Mangioris, Georgios; Panos, Georgios D

    2014-04-17

    A 16-year-old Brazilian female patient presented with blurring of vision in the right eye. Corrected visual acuity was OD 2/20, OS 20/20. Afferent pupillary defect was absent and anterior segment examination revealed anterior uveitis. Fundus examination showed light vitritis and a raised grey-white granuloma located at posterior pole with focal serous retinal detachment on optical coherence. Indocyacnine green angiography disclosed a complete mask effect in granuloma's area. Differential diagnoses were infectious (bacterial, viral, fungal and parasites) diseases, systemic inflammatory diseases, tumours. Blood serologies (HIV, toxoplasma, Borrelia, cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), rubeola) showed positive results for IgM and IgG for toxoplasma, and anterior chamber tap (PCR for toxoplasma, CMV, HSV, VZV) revealed toxoplasma DNA. Anti-toxoplasma therapy, pyrimethamine, sulfadiazine and calcium folinate, was administered immediately. On follow-up granuloma regression was observed, with complete visual restoration. This case demonstrates a clinically challenging posterior pole granuloma.

  5. Genetic polymorphisms of vitamin D receptor (VDR) in Fabry disease.

    PubMed

    Teitcher, Michael; Weinerman, Sarah; Whybra, Catharina; Beck, Michael; Sharon, Nir; Elstein, Deborah; Altarescu, Gheona

    2008-11-01

    Fabry disease, an X-linked inborn error of metabolism, is characterized by multi-organ involvement including cardiac signs of left ventricular hypertrophy and abnormal intima-medial (IMT) thickening of arteries, progressive renal failure, neurological involvement, and more. The vitamin D receptor (VDR) and an enzyme producing vitamin D3 result in an autocrine loop with direct effects on blood vessels. The purpose of this study is to assess VDR polymorphisms (BsmI, FokI, ApaI, and TaqI) relative to clinically important disease parameters using a disease-specific severity score (MSSI) and haplotype analysis. There were statistically significant differences between females (43% of 74 patients) and males in MSSI total scores, and in general and neurologic sub-scores. There appears to be a protective effect of the TaqI tt genotype so that there were significantly lower scores in clinical categories between those with the tt genotype versus those with the TT genotype. Multivariate models of haplotypes with MSSI scores reveal that T-A-f-B and t-a-F-b haplotypes of the VDR gene polymorphisms are significantly associated with variation in the Fabry phenotype. Despite the limitations of using the MSSI score as a clinical correlate, these results are provocative and further studies in larger cohorts with more males are recommended.

  6. Cardiac device implantation in Fabry disease

    PubMed Central

    Sené, Thomas; Lidove, Olivier; Sebbah, Joel; Darondel, Jean-Marc; Picard, Hervé; Aaron, Laurent; Fain, Olivier; Zenone, Thierry; Joly, Dominique; Charron, Philippe; Ziza, Jean-Marc

    2016-01-01

    Abstract The incidence and predictive factors of arrhythmias and/or conduction abnormalities (ACAs) requiring cardiac device (CD) implantation are poorly characterized in Fabry disease (FD). The aim of our retrospective study was to determine the prevalence, incidence, and factors associated with ACA requiring CD implantation in a monocentric cohort of patients with confirmed FD who were followed up in a department of internal medicine and reference center for FD. Forty-nine patients (20M, 29F) were included. Nine patients (4M, 5F; 18%) had at least one episode of ACA leading to device therapy. Six patients (4M/2F) required a pacemaker (PM) for sinus node dysfunction (n = 4) or atrioventricular disease (n = 2). One female patient required an internal cardioverter-defibrillator (ICD) to prevent sudden cardiac death because of nonsustained ventricular tachycardia (nSVT). One female patient required PM-ICD for sinus node dysfunction and nSVT. One patient underwent CD implantation before the diagnosis of FD. The annual rate of CD implantation was estimated at 1.90 per 100 person years. On univariate analysis at the end of the follow-up period, the factors associated with ACAs requiring CD implantation were as follows: delayed diagnosis of FD, delayed initiation of enzyme replacement therapy, age at the last follow-up visit, and severe multiorgan phenotype (hypertrophic cardiomyopathy, chronic kidney disease, and/or sensorineural hearing loss). On multivariate analysis, age at diagnosis of FD and age at the last follow-up visit were independently associated with an increased risk of ACAs requiring CD (P < 0.05). Considering the high frequency of ACAs requiring CD implantation and the risk of sudden death in patients with FD, regular monitoring is mandatory, especially in patients with a late diagnosis of FD and/or with a severe phenotype. Regular Holter ECGs, therapeutic education of patients, and deliverance of an emergency card including a phenotype

  7. Gastrointestinal involvement in Fabry disease. So important, yet often neglected.

    PubMed

    Politei, J; Thurberg, B L; Wallace, E; Warnock, D; Serebrinsky, G; Durand, C; Schenone, A B

    2016-01-01

    Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A which causes accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Gastrointestinal signs and symptoms-abdominal pain, nausea, diarrhea and diverticular disease--are some of the most frequently reported complaints in patients with Fabry disease but are often neglected. Gastrointestinal symptoms are due to intestinal dysmotility as well as impaired autonomic function, vasculopathy and myopathy. Since 2001, enzyme replacement therapy has been a mainstay in treatment of gastrointestinal symptoms of Fabry disease (FD), resulting in reduced gastrointestinal symptoms. Here, we report on four patients with Fabry disease (FD) who manifested early gastrointestinal involvement.

  8. How patient-centered do female physicians need to be? Analogue patients' satisfaction with male and female physicians' identical behaviors.

    PubMed

    Hall, Judith A; Roter, Debra L; Blanch-Hartigan, Danielle; Mast, Marianne Schmid; Pitegoff, Curtis A

    2015-01-01

    Previous research suggests that female physicians may not receive appropriate credit in patients' eyes for their patient-centered skills compared to their male counterparts. An experiment was conducted to determine whether a performance of higher (versus lower) verbal patient-centeredness would result in a greater difference in analogue patient satisfaction for male than female physicians. Two male and two female actors portrayed physicians speaking to a patient using high or low patient-centered scripts while not varying their nonverbal cues. One hundred ninety-two students served as analogue patients by assuming the patient role while watching one of the videos and rating their satisfaction and other evaluative responses to the physician. Greater verbal patient-centeredness had a stronger positive effect on satisfaction and evaluations for male than for female physicians. This pattern is consistent with the hypothesis that the different associations between patient-centeredness and patients' satisfaction for male versus female physicians occur because of the overlap between stereotypical female behavior and behaviors that comprise patient-centered medical care. If this is the case, high verbal patient-centered behavior by female physicians is not recognized as a marker of clinical competence, as it is for male physicians, but is rather seen as expected female behavior.

  9. Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study.

    PubMed

    Arends, Maarten; Wanner, Christoph; Hughes, Derralynn; Mehta, Atul; Oder, Daniel; Watkinson, Oliver T; Elliott, Perry M; Linthorst, Gabor E; Wijburg, Frits A; Biegstraaten, Marieke; Hollak, Carla E

    2016-12-15

    Fabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00; P<0.001; hazard ratio for women, 2.88, 95% confidence interval, 1.54 to 5.40; P<0.001). Furthermore, men with classical Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype (P<0.001). In conclusion, before treatment with enzyme replacement therapy, men with classical Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients.

  10. Metabolomic Discovery of Novel Urinary Galabiosylceramide Analogs as Fabry Disease Biomarkers

    NASA Astrophysics Data System (ADS)

    Boutin, Michel; Auray-Blais, Christiane

    2015-03-01

    Fabry disease is an X-linked, complex, multisystemic lysosomal storage disorder presenting marked phenotypic and genotypic variability among affected male and female patients. Glycosphingolipids, mainly globotriaosylceramide (Gb3) isoforms/analogs, globotriaosylsphingosine (lyso-Gb3) and analogs, as well as galabiosylceramide (Ga2) isoforms/analogs accumulate in the vascular endothelium, nerves, cardiomyocytes, renal glomerular and tubular epithelial cells, and biological fluids. The search for biomarkers reflecting disease severity and progression is still on-going. A metabolomic study using quadrupole time-of-flight mass spectrometry has revealed 22 galabiosylceramide isoforms/analogs in urine of untreated Fabry patients classified in seven groups according to their chemical structure: (1) Saturated fatty acid; (2) one extra double bond; (3) two extra double bonds; (4) hydroxylated saturated fatty acid; (5) hydroxylated fatty acid and one extra double bond; (6) hydrated sphingosine and hydroxylated fatty acid; (7) methylated amide linkage. Relative quantification of both Ga2 and Gb3 isoforms/analogs was performed. All these biomarkers are significantly more abundant in urine samples from untreated Fabry males compared with healthy male controls. A significant amount of Ga2 isoforms/analogs, accounting for 18% of all glycosphingolipids analyzed (Ga2 + Gb3 and respective isoforms/analogs), were present in urine of Fabry patients. Gb3 isoforms containing saturated fatty acids are the most abundant (60.9%) compared with 26.3% for Ga2. A comparison between Ga2 isoforms/analogs and their Gb3 counterparts also showed that the proportion of analogs with hydroxylated fatty acids is significantly greater for Ga2 (35.8%) compared with Gb3 (1.9%). These results suggest different biological pathways involved in the synthesis and/or degradation of Gb3 and Ga2 metabolites.

  11. Enzyme replacement therapy for Fabry disease: a systematic review of available evidence.

    PubMed

    Schaefer, Roland M; Tylki-Szymańska, Anna; Hilz, Max J

    2009-11-12

    Fabry disease is a progressive and life-threatening glycolipid storage disorder affecting both males and females. The primary driver of the disease is the accumulation of glycolipids (globotriaosylceramide [GL-3]) in a variety of cell types, including vascular endothelial cells, a range of renal cell types, cardiomyocytes and neurons, which is caused by deficient activity of the lysosomal enzyme, alpha-galactosidase. The disease typically presents during childhood or adolescence. First manifestations reflect involvement of small nerve fibres of the peripheral and autonomic nervous systems. With age, severe complications involving the kidneys, heart and brain cause considerable morbidity and premature death. Outside the US, enzyme replacement therapy (ERT) with agalsidase alfa 0.2 mg/kg every other week (EOW) and agalsidase beta 1.0 mg/kg EOW is available for the treatment of patients with Fabry disease, while agalsidase beta 1.0 mg/kg EOW is the only approved drug in the US. To analyse the evidence for ERT, a systematic review of the literature was performed to identify prospectively designed randomized, controlled trials (RCTs) and open-label studies on the efficacy of agalsidase alfa and agalsidase beta. MEDLINE and EMBASE databases were searched; inclusion criteria for the systematic review were prospectively designed clinical studies evaluating ERT with quantifiable endpoints: double-blind and open-label studies were eligible. Exclusion criteria were review articles, case reports, case studies, letters to the editor and articles based on registry data (Fabry Outcome Survey or Fabry Registry). In addition, any studies with a retrospective design or data based on post hoc analyses were excluded. The evidence was reviewed with respect to the clinical benefits of ERT at the level of the end organ. A total of 9 RCTs and 23 open-label studies were identified for inclusion. The efficacy of ERT in Fabry disease has been measured against a variety of endpoints, the

  12. Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.

    PubMed

    Byeon, Seul Kee; Kim, Jin Yong; Lee, Jin-Sung; Moon, Myeong Hee

    2016-03-01

    A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

  13. [The Fabry's Disease Cardiomyopathy as Differential Diagnosis of Acute Coronary Syndrome].

    PubMed

    Oder, Daniel; Störk, Stefan; Wanner, Christoph; Ertl, Georg; Weidemann, Frank; Nordbeck, Peter

    2017-03-01

    The progressive cardiomyopathy in patients with Fabry disease is often accompanied by angina pectoris and elevated levels of high-sensitive troponin T (hs-TnT), potentially mimicking acute coronary syndrome. Here, we present to representative cases with focus on clinical, diagnostic and therapeutic settings. An overview on the cardiomyopathy associated with Fabry disease and its role as differential diagnosis of acute coronary syndrome is provided. Fabry cardiomyopathy might exhibit similar clinical and biochemical constellations as seen in acute coronary syndrome. Thus, Fabry cardiomyopathy should be considered a differential diagnosis in acute coronary syndrome, particularly in patients demonstrating left ventricular hypertrophy of unknown origin.

  14. Progressive renal failure despite long-term biweekly enzyme replacement therapy in a patient with Fabry disease secondary to a new α-galactosidase mutation of Leu311Arg (L311R).

    PubMed

    Suzuki, Keisuke; Miura, Naoto; Kitagawa, Wataru; Suzuki, Shinkichi; Komatsuda, Atsushi; Nishikawa, Kazuhiro; Watanabe, Daisuke; Imai, Hirokazu

    2011-12-01

    A 37-year-old Japanese man affected by Fabry disease secondary to a novel mutation of Leu311Arg (L311R) in α-galactosidase demonstrated progressive renal failure despite biweekly enzyme replacement therapy (ERT) for approximately 10 years. Kidney biopsy revealed foamy glomerular epithelial cells, compatible with the typical pathologic features of Fabry disease. The patient entered a phase III study of Replagal (agalsidase alfa) in 2001, allowing him to continue ERT with biweekly dosing for almost 10 years. During 2 years of that period, he was continued on Fabrazyme (agalsidase beta) biweekly dosing. His estimated GFR was calculated to decrease by 9.9 mL/min/1.73 m(2) per year. Patients with Fabry disease have been reported to have a mean decrease in GFR of 12.2 ± 8.1 mL/min/1.73 m(2) per year. This result suggests that biweekly ERT is only mildly effective at preventing loss of kidney function.

  15. Questioning the Pathogenic Role of the GLA p.Ala143Thr "Mutation" in Fabry Disease: Implications for Screening Studies and ERT.

    PubMed

    Terryn, W; Vanholder, R; Hemelsoet, D; Leroy, B P; Van Biesen, W; De Schoenmakere, G; Wuyts, B; Claes, K; De Backer, J; De Paepe, G; Fogo, A; Praet, M; Poppe, B

    2013-01-01

    Fabry disease is an X-linked inborn error of glycosphingolipid metabolism caused by quantitative or qualitative defects in the lysosomal enzyme alfa-Galactosidase A (aGAL A), ultimately resulting in vital organ dysfunction. Mainly the kidneys, the heart, and the central nervous system are involved. While the classical phenotype of Fabry disease is readily recognizable, screening studies have identified clinical variants. Here, we report the phenotype associated with the GLA p.Ala143Thr (c.427G>A) mutation in 12 patients aged 42-83 years. None of the patients had classical Fabry signs or symptoms as angiokeratoma, hypohidrosis, acroparesthesia, or cornea verticillata. Possible Fabry manifestations were renal failure (5/12), stroke (7/12), and left ventricular hypertrophy (5/12), but these were not necessarily attributable to the p.Ala143Thr mutation, as a cardiac biopsy in one female and left ventricular hypertrophy and kidney biopsies in two males with renal failure and microalbuminuria lacked Gb-3 deposits. The literature data on this mutation as well as data collected in the Fabry Outcome Survey (FOS) database confirm these findings. The association of renal failure, stroke, and left ventricular hypertrophy with this mutation could be the result of selection bias, as most patients were detected in screening studies.We conclude that care should be taken with attribution of vital organ dysfunction to GLA sequence alterations. In case of the p.Ala143Thr mutation, and possibly also other mutations associated with an attenuated phenotype, diagnostic tools such as biopsy and imaging should critically evaluate the relation of end-organ failure with Fabry disease, as this has important consequences for enzyme replacement therapy.

  16. Impact of cardio-renal syndrome on adverse outcomes in patients with Fabry disease in a long-term follow-up.

    PubMed

    Siegenthaler, M; Huynh-Do, U; Krayenbuehl, P; Pollock, E; Widmer, U; Debaix, H; Olinger, E; Frank, M; Namdar, M; Ruschitzka, F; Nowak, A

    2017-09-19

    Fabry disease (FD) is a rare X-linked lysosomal storage disease with a deficiency of α-galactosidase A leading to progressive sphingolipid accumulation in different organs, among them heart and kidney. We evaluated the impact of cardio-renal syndrome (CRS) on the incidence of major cardiovascular complications and death in a prospective FD cohort. A total of 104 genetically proven FD patients were annually followed at the University Hospitals Zurich and Bern. The main outcome was a composite of incident renal replacement therapy (RRT), hospitalisation due to decompensated Heart Failure, new onset atrial fibrillation, pacemaker/ICD implantation, stroke/TIA and death. Estimated glomerular filtration rate (eGFR) and left ventricular myocardial mass index (LVMMI) where explored as the primary exposure variables. During the median follow-up of 103 [59-155] months, events occurred in 27 patients. In a Cox regression analysis, both higher LVMMI and lower eGFR were independently associated with a greater risk of developing adverse events after adjustment for multiple confounders (HR 1.67 [1.04-2.73] P=0.03 per SD increase in LVMMI, HR 0.45 [0.25-0.83], P=0.01 per SD decrease in eGFR). In patients with CRS, the risk to develop events was significantly increased if adjusted for demographics and RRT (HR 4.46 [1.07-18.62], P=0.04), approaching significance if additionally adjusted for hypertension (HR 4.05 [0.95-17.29], P=0.06). In Kaplan-Meier-Analysis, the poorest event-free survival was observed among patients with CRS. CRS was associated with a high risk to develop cardiovascular complications and death, emphasizing the importance of its prevention and early recognition. A focus on cardio-reno-protective therapies is crucial. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Multiple parapelvic cysts in Fabry disease.

    PubMed

    Azancot, María A; Vila, Josefa; Domínguez, Carmen; Serres, Xavier; Espinel, Eugenia

    2016-01-01

    Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis.

  18. Correction in trans for Fabry disease: expression, secretion and uptake of alpha-galactosidase A in patient-derived cells driven by a high-titer recombinant retroviral vector.

    PubMed Central

    Medin, J A; Tudor, M; Simovitch, R; Quirk, J M; Jacobson, S; Murray, G J; Brady, R O

    1996-01-01

    Fabry disease is an X-linked metabolic disorder due to a deficiency of alpha-galactosidase A (alpha-gal A; EC 3.2.1.22). Patients accumulate glycosphingolipids with terminal alpha-galactosyl residues that come from intracellular synthesis, circulating metabolites, or from the biodegradation Of senescent cells. Patients eventually succumb to renal, cardio-, or cerebrovascular disease. No specific therapy exists. One possible approach to ameliorating this disorder is to target corrective gene transfer therapy to circulating hematopoietic cells. Toward this end, an amphotropic virus-producer cell line has been developed that produces a high titer (>10(6) i.p. per ml) recombinant retrovirus constructed to transduce and correct target cells. Virus-producer cells also demonstrate expression of large amounts of both intracellular and secreted alpha-gal A. To examine the utility of this therapeutic vector, skin fibroblasts from Fabry patients were corrected for the metabolic defect by infection with this recombinant virus and secreted enzyme was observed. Furthermore, the secreted enzyme was found to be taken up by uncorrected cells in a mannose-6-phosphate receptor-dependent manner. In related experiments, immortalized B cell lines from Fabry patients, created as a hematologic delivery test system, were transduced. As with the fibroblasts, transduced patient B cell lines demonstrated both endogenous enzyme correction and a small amount of secretion together with uptake by uncorrected cells. These studies demonstrate that endogenous metabolic correction in transduced cells, combined with secretion, may provide a continuous source of corrective material in trans to unmodified patient bystander cells (metabolic cooperativity). Images Fig. 2 Fig. 3 Fig. 4 Fig. 6 PMID:8755577

  19. Fabry nephropathy: a review - how can we optimize the management of Fabry nephropathy?

    PubMed

    Waldek, Stephen; Feriozzi, Sandro

    2014-05-06

    Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment.

  20. Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy?

    PubMed Central

    2014-01-01

    Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment. PMID:24886109

  1. Prevalence of Fabry disease in a predominantly hypertensive population with left ventricular hypertrophy.

    PubMed

    Terryn, Wim; Deschoenmakere, Gert; De Keyser, Jan; Meersseman, Wouter; Van Biesen, Wim; Wuyts, Brigitte; Hemelsoet, Dimitri; Pascale, Hilbert; De Backer, Julie; De Paepe, An; Poppe, Bruce; Vanholder, Raymond

    2013-09-10

    Patients with Fabry disease (FD) develop progressive left ventricular hypertrophy (LVH). In screening studies in patients with LVH, the prevalence of FD ranges from 0 to 12%. This variability is attributable to different factors like diverging inclusion and exclusion criteria, the evaluation of selected populations and suboptimal screening methods. In this study, we aimed to determine the prevalence of FD in an unselected population of everyday clinical practice presenting LVH, defined as a maximal end-diastolic septal or posterior wall thickness ≥ 13 mm, without exclusion of patients with arterial hypertension or valvular pathology, and using optimal screening methods. In adult males, a two-tier approach was used; α-Galactosidase A (aGAL A) activity was measured using a dried bloodspot test (DBS) and diagnosis was confirmed by mutation analysis of the GLA gene. In females, mutation analysis was the primary screening tool. 362 men and 178 women were screened. Six patients were diagnosed with a genetic sequence alteration of the GLA gene. One man had a novel mutation, GLA p.Ala5Glu (c.44C>A), presenting as classical FD. Another man and three women had the previously described GLA p.Ala143Thr (c.427G>A) mutation, which generally presents as an attenuated phenotype. One woman had a novel sequence alteration c.639+6A>C, which appeared to be a polymorphism. All true Fabry patients had arterial hypertension (AHT), and one had hypertrophic obstructive cardiomyopathy (HOCM). In a group of unselected patients with LVH, we found a prevalence of Fabry disease of 0.9%. AHT or type of hypertrophy should not be an exclusion criterion for screening for FD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. A novel mutation of α-galactosidase A gene causes Fabry disease mimicking primary erythromelalgia in a Chinese family.

    PubMed

    Ge, Wei; Wei, Bin; Zhu, Hao; Miao, Zhigang; Zhang, Weimin; Leng, Cuihua; Li, Jizhen; Zhang, Dan; Sun, Miao; Xu, Xingshun

    2017-05-01

    Fabry disease is an X-linked genetic disorder caused by the mutations of α-galactosidase A (GLA, MIM 300644) gene presenting with various clinical symptoms including small-fiber peripheral neuropathy and limb burning pain. Here, we reported a Chinese pedigree with the initial diagnosis of primary erythromelalgia in an autosomal dominant (AD)-inherited pattern. Mutation analysis of SCN9A and GLA genes by direct sequencing and functional analysis of a novel mutation of GLA in cells were performed. Our data did not show any pathological mutations in SCN9A gene; however, a novel missense mutation c.139T>C (p.W47R) of GLA was identified in a male proband as well as two female carriers in this family. Enzyme assay of α-galactosidase A activity showed deficient enzyme activity in male patients and female carriers, further confirming the diagnosis of Fabry disease. Finally, a functional analysis indicated that the replacement of the 47th amino acid tryptophan (W47) with arginine (W47R) or glycine (W47G) led to reduced activity of α-galactosidase A in 293T cells. Therefore, these findings demonstrated that the novel mutation p.W47R of GLA is the cause of Fabry disease. Because Fabry disease and primary erythromelalgia share similar symptoms, it is a good strategy for clinical physicians to perform genetic mutation screenings on both SCN9A and GLA genes in those patients with limb burning pain but without a clear inheritant pattern.

  3. Potential role of vitamin D deficiency on Fabry cardiomyopathy.

    PubMed

    Drechsler, Christiane; Schmiedeke, Benjamin; Niemann, Markus; Schmiedeke, Daniel; Krämer, Johannes; Turkin, Irina; Blouin, Katja; Emmert, Andrea; Pilz, Stefan; Obermayer-Pietsch, Barbara; Weidemann, Frank; Breunig, Frank; Wanner, Christoph

    2014-03-01

    Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy. This study investigated the vitamin D status and its association with LV mass and adverse clinical symptoms in patients with Fabry disease. 25-hydroxyvitamin D (25[OH]D) was measured in 111 patients who were genetically proven to have Fabry disease. LV mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analyses, associations with adverse clinical outcomes were determined by linear and binary logistic regression analyses, respectively, and were adjusted for age, sex, BMI and season. Patients had a mean age of 40 ± 13 years (42% males), and a mean 25(OH)D of 23.5 ± 11.4 ng/ml. Those with overt vitamin D deficiency (25[OH]D ≤ 15 ng/ml) had an adjusted six fold higher risk of cardiomyopathy, compared to those with sufficient 25(OH)D levels >30 ng/ml (p = 0.04). The mean LV mass was distinctively different with 170 ± 75 g in deficient, 154 ± 60 g in moderately deficient and 128 ± 58 g in vitamin D sufficient patients (p = 0.01). With increasing severity of vitamin D deficiency, the median levels of proteinuria increased, as well as the prevalences of depression, edema, cornea verticillata and the need for medical pain therapy. In conclusion, vitamin D deficiency was strongly associated with cardiomyopathy and adverse clinical symptoms in patients with Fabry disease. Whether vitamin D supplementation improves complications of Fabry disease, requires a randomized controlled trial.

  4. MRI in acute cerebral ischemia of the young: the Stroke in Young Fabry Patients (sifap1) Study.

    PubMed

    Fazekas, Franz; Enzinger, Christian; Schmidt, Reinhold; Dichgans, Martin; Gaertner, Beate; Jungehulsing, Gerhard J; Hennerici, Michael G; Heuschmann, Peter; Holzhausen, Martin; Kaps, Manfred; Kessler, Christof; Martus, Peter; Putaala, Jukka; Ropele, Stefan; Tanislav, Christian; Tatlisumak, Turgut; Norrving, Bo; Rolfs, Arndt

    2013-11-26

    We focused on cerebral imaging findings in a large cohort of young patients with a symptomatic ischemic cerebrovascular event (CVE) to extract relevant pathophysiologic and clinical information. We analyzed the scans of 2,979 patients (aged 18-55 years) enrolled in the sifap1 project with clinical evidence of ischemic stroke (IS) or clinically defined TIA in whom MRI, including diffusion-weighted imaging, was obtained within 10 days of the CVE. Age groups were categorized as 18-34, 35-44, and 45-55 years. We compared age- and sex-specific proportions of infarct features, white matter hyperintensities, and old microbleeds. Acute infarcts were identified in 1,914 of 2,264 patients (84.5%) with IS and 101 of 715 patients (14.1%) with TIA. Among patients with IS, younger age was significantly associated with acute infarcts in the posterior circulation, while anterior circulation infarcts and acute lacunar infarcts were more frequent in older age groups. One or more old infarcts were present in 26.8% of IS and 17.1% of TIA patients. This rate remained high even after excluding patients with a prior CVE (IS, 21.7%; TIA, 9.9%). The prevailing type of old infarction was territorial in patients younger than 45 years and lacunar in those aged 45 years or older. The frequency of white matter hyperintensities (46.4%) and their severity was positively associated with age. Old microbleeds were infrequent (7.2%). Young adults show a high frequency of preexisting and clinically silent infarcts and a relative preference for acute ischemia in the posterior circulation. Findings suggesting small-vessel disease become apparent at age 45 years and older.

  5. Superior mentalizing abilities of female patients with schizophrenia.

    PubMed

    Abu-Akel, Ahmad; Bo, Sune

    2013-12-30

    Mentalizing abilities are severely disrupted in patients with schizophrenia, but gender-related differences in this domain are virtually unexplored. Given the importance of these abilities in understanding psychopathology, social functioning and outcome, this study aimed to examine the mentalizing abilities of male and female patients with schizophrenia. The cognitive and affective mentalizing abilities of self and other of clinically stable male and female patients with schizophrenia were analyzed using the abbreviated version of the Metacognitive Assessment Scale (MAS-A). Compared to their male counterparts, the female patients demonstrated superior overall mentalizing abilities. This advantage was also evident when mentalizing about the Self or the Other. When examining cognitive versus affective mentalizing, women were significantly better in their ability to attribute and understand the affective mental states of others. These differences were unrelated to intelligence or psychopathology. The superior mentalizing abilities of female patients extend gender-related differences in schizophrenia to include social cognition. This suggests that our current knowledge of socio-cognitive abilities in schizophrenia is generalizable to male but not to female patients. The findings also provide important insights to understanding how etiological differences affect social cognition. Awareness to such differences has important implications for diagnosis and clinical treatment.

  6. Revision Stapedectomy in a Female Patient with Inner Ear Malformation

    PubMed Central

    Patel, Tirth R.; Moberly, Aaron C.

    2016-01-01

    Objectives. We describe an unusual case of surgical management of congenital mixed hearing loss in a female patient with inner ear malformation. This report outlines the role of temporal bone imaging and previous surgical history in evaluating a patient's risk of perilymph gusher during stapes surgery. Methods. A 68-year-old female patient with a history of profound bilateral mixed hearing loss due to ossicular and cochlear malformation presented to our otology clinic. She had undergone multiple unsuccessful previous ear surgeries. Computed tomography revealed bilateral inner ear malformations. She elected to proceed with revision stapedectomy. Results. The patient received modest benefit to hearing, and no operative complications occurred. Conclusions. Although stapedectomy has been shown to improve hearing in patients with stapes fixation, there is risk of perilymph gusher in patients with inner ear abnormalities. Evaluation and counseling of the risk of gusher during stapes surgery should be done on a case-by-case basis. PMID:27144044

  7. High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3 ) in Urine Collected on Filter Paper.

    PubMed

    Auray-Blais, Christiane; Lavoie, Pamela; Boutin, Michel; Abaoui, Mona

    2017-04-06

    Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000. Its complexity lies in the marked genotypic and phenotypic heterogeneity. Despite the fact that it is an X-linked disease, more than 600 mutations affect both males and females. In fact, some females may be affected as severely as males. The purpose of this protocol is to focus on the high-risk screening of patients who might have Fabry disease using a simple, rapid, non-invasive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for urinary globotriaosylceramide (Gb3 ) analysis. Urine filter paper samples are easily collected at home by patients and sent by regular mail. This method has been successfully used for high-risk screening of patients with ophthalmologic manifestations and in an on-going study for high-risk screening of Fabry disease in patients with chronic kidney diseases. © 2017 by John Wiley & Sons, Inc.

  8. Efficacy and safety of febuxostat in elderly female patients

    PubMed Central

    Mizuno, Tomohiro; Hayashi, Takahiro; Hikosaka, Sayo; Shimabukuro, Yuka; Murase, Maho; Takahashi, Kazuo; Hayashi, Hiroki; Yuzawa, Yukio; Nagamatsu, Tadashi; Yamada, Shigeki

    2014-01-01

    Background Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear. Objective The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients. Methods We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. Results We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups. Conclusion Our findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent. PMID:25214776

  9. Efficacy and safety of febuxostat in elderly female patients.

    PubMed

    Mizuno, Tomohiro; Hayashi, Takahiro; Hikosaka, Sayo; Shimabukuro, Yuka; Murase, Maho; Takahashi, Kazuo; Hayashi, Hiroki; Yuzawa, Yukio; Nagamatsu, Tadashi; Yamada, Shigeki

    2014-01-01

    Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear. The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients. We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups. Our findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent.

  10. Female sexual dysfunction among Egyptian patients with chronic hepatitis C.

    PubMed

    Elshimi, Esam; Morad, Wesam; Mohamad, Noha Ezzat; Shebl, Nashwa; Waked, Imam

    2014-03-01

    Chronic hepatitis C is associated with many extrahepatic manifestations that impact and impair the quality of life. Hepatitis C virus (HCV) infection has a high prevalence in Egypt and carries with the diagnosis many social impacts and stigmatization correlates that further impair social function. This might negatively impact patients and their sexual function. Sexuality and sexual function have not been studied well in patients with HCV, especially in women. To investigate sexual dysfunction in Egyptian women with chronic hepatitis C. Female Sexual Function Index (FSFI) scores of patients with hepatitis C, both total and for individual domains, were compared with those of controls. The self-administered FSFI questionnaire was completed by 112 sexually active female patients with chronic hepatitis C without liver cirrhosis prior to initiation of therapy by pegylated interferon and ribavirin. Their results were compared to those of 225 age- and socioeconomic class-matched sexually active healthy females. Significantly more patients than controls had questionnaire scores below the threshold of female sexual dysfunction (FSD) (79% vs. 21%, P < 0.05), and the mean total score for the patients was significantly lower than that for controls (19.54 ± 6.2 vs. 28.43 ± 4.9 P < 0.001). The patients' scores in all domains of the questionnaire were significantly lower than those of the controls. Chronic hepatitis C negatively impacts female sexual function, affecting all domains of the sex cycle; this warrants further studies and needs to be addressed as part of a comprehensive therapy plan to improve patients' quality of life. © 2013 International Society for Sexual Medicine.

  11. Fabry disease: multidisciplinary evaluation after 10 years of treatment with agalsidase Beta.

    PubMed

    Juan, Politei; Hernan, Amartino; Beatriz, Schenone Andrea; Gustavo, Cabrera; Antonio, Michref; Eduardo, Tanus; Raul, Dominguez; Margarita, Larralde; Mariana, Blanco; Daniela, Gaggioli; Marina, Szlago

    2014-01-01

    Fabry disease is an X linked disorder of metabolism due to deficient α-galactosidase A activity. Enzyme replacement therapy (ERT) with agalsidase Beta was approved by EMA in 2001 and FDA in 2003. Six patients were enrolled. Baseline data was measured for renal, cardiac, and cerebrovascular functioning. We compared baseline quality of life scales with the current results. These parameters were assessed during the 10 years of follow-up period. Before ERT four patients showed normal eGFR, one stage 2 of CKD, and one hyperfiltration stage. All presented microalbuminuria and just two cases showed proteinuria. After 10 years of ERT, no patient showed decrease in renal functioning. One patient decreased from proteinuria to microalbuminuria range. Before treatment one case showed left ventricular (LV) hypertrophy and LV Mass Index was abnormal in two female patients. After 10 years echocardiographic values did not present progression to LVH and one female showed regression to normal values of LV posterior wall and interventricular septum. Brain MRI showed ischemic lesions in one female and vertebrobasilar dolichoectasia in one male. From baseline and during the follow-up period MRI did not progress to new ischemic lesions and there were no clinical signs of cerebrovascular damage. After 10 years quality of life showed improvement in all domains measured. Early treatment of agalsidase Beta is related to a better outcome regarding stability and regression of signs and symptoms in Fabry disease. Our results in patients with mild organ involvement showed good outcomes and support an early and continuous ERT.

  12. Fabry disease, respiratory symptoms, and airway limitation - a systematic review.

    PubMed

    Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke

    2015-01-01

    Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A, resulting in accumulation of glycosphingolipids in multiple organs, primarily heart, kidneys, skin, CNS, and lungs. A systematic literature search was performed using the PubMed database, leading to a total number of 154 hits. Due to language restriction, this number was reduced to 135; 53 papers did not concern Fabry disease, 19 were either animal studies or gene therapy studies, and 36 papers did not have lung involvement in Fabry disease as a topic. The remaining 27 articles were relevant for this review. The current literature concerning lung manifestations describes various respiratory symptoms such as dyspnoea or shortness of breath, wheezing, and dry cough. These symptoms are often related to cardiac involvement in Fabry disease as respiratory examinations are seldom performed. Pulmonary function tests primarily show obstructive airway limitation, but a few articles also report of patients with restrictive limitation and a mixture of both. No significant association has been found between smoking and the development of symptoms or spirometry abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X-ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed by high-resolution CT has not been significantly correlated with lung spirometry. Consistent findings have not been shown in the current literature. Pulmonary function tests and registration of symptoms showed various results; however, there is a trend towards obstructive airway limitation in patients with Fabry disease. Further studies are needed to evaluate pathogenesis, progression, and the effects of treatment.

  13. Fabry disease simulating Crohn's ileitis.

    PubMed

    Rubio, Carlos A; Villnow, Elizabeth; Sundelin, Birgitta; Eriksson, Elina; Dolapcsiev, Karoli; Björk, Jan; Befrits, Ragnar; Tengvar, Magnus; Iversen, Henrik

    2014-05-01

    Fabry disease is an inherited (X-linked) lysosomal storage disorder caused by deficiency of α-galactosidase A, leading to accumulation of globotriaosylceramide in various tissues. A 57-year-old male with a family history and laboratory findings of Fabry disease, was consulted for severe abdominal pain, undulating pyrexia, weight loss and diarrhea. The tentative clinical diagnosis of Crohn's ileitis was supported at computed tomographic examination, at laparotomy and at inspection of the resected ileal segment. Histology revealed chronic and acute inflammation, thick-walled occluded vessels, fibrosis and characteristic bi-refringent lamellar deposits of globotriaosylceramide and calcifications. Multi-nucleated giant cells contained phagocytized bi-refringent material. Transmission electron microscopy showed cells with irregular cytoplasmic bodies displaying distinctive zebra-like lamellar structures. It is submitted that the gastrointestinal phenotype of Fabry disease may concur with symptoms resembling abdominal Crohn's disease.

  14. Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

    PubMed

    Tuttolomondo, Antonino; Simonetta, Irene; Duro, Giovanni; Pecoraro, Rosaria; Miceli, Salvatore; Colomba, Paolo; Zizzo, Carmela; Nucera, Antonia; Daidone, Mario; Di Chiara, Tiziana; Scaglione, Rosario; Della Corte, Vittoriano; Corpora, Francesca; Vogiatzis, Danai; Pinto, Antonio

    2017-09-22

    Anderson-Fabry disease (AFD) is an inborn lysosomal enzymopathy resulting from the deficient or absent activity of the lysosomal exogalactohydrolase, α-galactosidase A. This deficiency, results in the altered metabolism of glycosphingolipids which leads to their accumulation in lysosomes, thus to cellular and vascular dysfunction. To date, numerous mutations (according to recent data more than 1000 mutations) have been reported in the GLA intronic and exonic mutations. Traditionally, clinical manifestations are more severe in affected hemizygous males than in females. Nevertheless, recent studies have described severe organ dysfunction in women. This study reports clinical, biochemical, and molecular findings of the members of three Sicilian families. The clinical history of these patients highlights a remarkable interfamilial and intrafamilial phenotypic variability which characterizes Fabry disease relative to target organs and severity of clinical manifestations. Our findings, in agreement with previous data, report a little genotype-phenotype correlation for the disease, suggesting that the wide phenotypic variability of Anderson-Fabry disease is not completely ascribable to different gene mutations but other factors and mechanisms seem to be involved in the pathogenesis and clinical expression of the disease. Moreover, this study emphasies the importance of pedigree analysis in the family of each proband for identifying other possibly affected relatives.

  15. Intermittent self-catheterisation and the female patient.

    PubMed

    Bennett, Elisabeth

    The use of intermittent self-catheterisation (ISC) in the treatment of bladder disorders has increased in recent years. Manufacturers have also been developing a range of new catheters to make the procedure safer, easier and more comfortable for the patient. Patients may be taught intermittent self-catheterisation in the hospital, clinic or home setting. The amount of follow up and support given varies widely. Recent government policies aim to empower the patient to make decisions about their care (DoH 2000a, DoH 2001a). This article examines the factors that affect female patients whose bladder dysfunction is managed by ISC.

  16. Acne in the adult female patient: a practical approach.

    PubMed

    Kamangar, Faranak; Shinkai, Kanade

    2012-10-01

    Acne vulgaris is a common reason why adult women present to dermatologists and can be a clinical challenge to treat. It may also be an important sign of an underlying endocrine disease such as Polycystic Ovary Syndrome (PCOS). Although standard acne therapies can be successfully used to treat acne in adult female patients, hormonal treatment is a safe and effective therapeutic option that may provide an opportunity to better target acne in this population, even when other systemic therapies have failed. In this article, a practical approach to the adult female patient with acne will be reviewed to enhance the dermatologist's ability to use hormonal acne therapies and to better identify and evaluate patients with acne in the setting of a possible endocrine disorder.

  17. Body dysmorphic disorder in female Swedish dermatology patients.

    PubMed

    Brohede, Sabina; Wyon, Yvonne; Wingren, Gun; Wijma, Barbro; Wijma, Klaas

    2017-09-27

    Individuals with body dysmorphic disorder (BDD) are highly distressed and impaired owing to perceived defects in their physical appearance that are not noticeable to others. They are frequently concerned about their skin and often present to dermatologists rather than psychiatrists. However, BDD patients attending dermatology clinics may be at risk of not receiving an appropriate assessment and beneficial treatment. The aims of this study were to estimate the BDD prevalence rate among Swedish female dermatology patients and to assess the psychological condition of BDD patients compared to that of other dermatology patients. The occurrence of BDD was estimated using the Body Dysmorphic Disorder Questionnaire (BDDQ), a validated self-report measure for BDD. Symptoms of depression and anxiety were measured by the Hospital Anxiety and Depression Scale (HADS), and quality of life was assessed using the Dermatology Life Quality Index (DLQI). The prevalence rate of BDD among female Swedish dermatology patients was 4.9% (95% CI 3.2-7.4). Anxiety (HADS A ≥ 11) was 4-fold more commonly reported by patients with positive BDD screening (48% vs. 11%), and depression (HADS D ≥ 11) was over 10-fold more common in patients with positive BDD screening (19% vs. 1.8%) (P < 0.001). The median DLQI score was 18 in the BDD group, compared to a score of 4 in the non-BDD group (P < 0.001). Our results indicate that BDD is fairly common among female Swedish dermatology patients (4.9%) and that BDD patients have high levels of depression and anxiety and severely impaired quality of life. © 2017 The International Society of Dermatology.

  18. Clinical prodromes of neurodegeneration in Anderson-Fabry disease

    PubMed Central

    Hughes, Derralynn; Milligan, Alan; Richfield, Linda; Reichmann, Heinz; Mehta, Atul; Schapira, Anthony H.V.

    2015-01-01

    Objective: To estimate the prevalence of prodromal clinical features of neurodegeneration in patients with Anderson-Fabry disease (AFD) in comparison to age-matched controls. Methods: This is a single-center, prospective, cross-sectional study in 167 participants (60 heterozygous females and 50 hemizygous males with genetically confirmed AFD, 57 age-matched controls) using a clinical screening program consisting of structured interview, quantitative tests of motor function, and assessments of cognition, depression, olfaction, orthostatic intolerance, pain, REM sleep behavior disorder, and daytime sleepiness. Results: In comparison to age-matched controls (mean age 48.3 years), patients with AFD (mean age 49.0 years) showed slower gait and transfer speed, poorer fine manual dexterity, and lower hand speed, which was independent of focal symptoms due to cerebrovascular disease. Patients with AFD were more severely affected by depression, pain, and daytime sleepiness and had a lower quality of life. These motor and nonmotor manifestations significantly correlated with clinical disease severity. However, patients with AFD did not reveal extrapyramidal motor features or signs of significant cognitive impairment, hyposmia, orthostatic intolerance, or REM sleep behavior disorder, which commonly precede later neurodegenerative disease. In our cohort, there were no differences in neurologic manifestations of AFD between heterozygous females and hemizygous males. Conclusions: Aside from cerebrovascular manifestations and small fiber neuropathy, AFD results in a distinct neurologic phenotype comprising poorer motor performance and specific nonmotor features. In contrast to functional loss of glucocerebrosidase in Gaucher disease, α-galactosidase deficiency in AFD is not associated with a typical cluster of clinical features prodromal for neurodegenerative diseases, such as Parkinson disease. PMID:25762709

  19. High Variability of Fabry Disease Manifestations in an Extended Italian Family

    PubMed Central

    Cammarata, Giuseppe; Fatuzzo, Pasquale; Rodolico, Margherita Stefania; Colomba, Paolo; Sicurella, Luigi; Iemolo, Francesco; Zizzo, Carmela; Bartolotta, Caterina; Duro, Giovanni

    2015-01-01

    Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolase α-galactosidase A (α-GAL). The impairment of α-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences in α-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease. PMID:25977923

  20. Autograft Choice in Young Female Patients: Patella Tendon versus Hamstring.

    PubMed

    Shakked, Rachel; Weinberg, Maxwell; Capo, Jason; Jazrawi, Laith; Strauss, Eric

    2017-03-01

    With the increasing incidence of anterior cruciate ligament (ACL) reconstruction in women and younger patients, the optimal graft choice in the young female patient has become the subject of much debate. This study aimed to evaluate patient-reported outcomes, objective knee stability, complication rates, and the incidence of failure after ACL reconstruction using bone-patellar tendon-bone (BPTB) autograft compared with hamstring (HS) autograft in young female patients. Female patients who underwent primary ACL reconstruction with BPTB or HS autograft between ages 15 and 25 years were identified. Medical records were reviewed for postoperative complications and subsequent procedures on the operative knee. Patients were evaluated with functional surveys, physical examination including Lachman and pivot-shift tests, and arthrometric testing with a KT-1000 arthrometer. There were 37 patients in the BPTB group and 28 patients in the HS group. For patients who did not undergo revision, significant differences were not found in visual analog score (p = 0.94), Lysholm score (p = 0.81), Kujala score (p = 0.85), or Tegner level (p = 0.81). No difference was detected in the rate of return to a level of activity at or above the same level prior to injury (p = 0.31). Significantly more patients in the BPTB group were graded 1a Lachman and negative pivot shift compared with the HS group (p < 0.001). There was a significant difference in mean side-to-side manual maximum arthrometric testing (p < 0.001). There were significantly fewer subsequent procedures and a lower rate of graft failures in the BPTB group. We detected no difference in subjective functional outcomes following ACL reconstruction. However, a higher failure rate in the HS reconstructions and greater laxity by arthrometric testing may indicate increased objective stability with the use of BPTB autograft in the young female patient population. The level of evidence for this article is

  1. Female sexual dysfunction in patients with endometriosis: Indian scenario

    PubMed Central

    Mishra, Vineet V.; Nanda, Sakshi; Gandhi, Khushali; Aggarwal, Rohina; Choudhary, Sumesh; Gondhali, Raveendra

    2016-01-01

    BACKGROUND: Female sexual dysfunction (FSD) in Indian women is often overlooked due to cultural beliefs and considered as social taboos. Sexuality is an important and integral part of life. There are many causes of sexual dysfunction, but the prevalence of FSD in endometriotic patients is still underdiagnosed. MATERIALS AND METHODS: Study design - Cross-sectional observational study conducted at tertiary care center, from June 2015 to March 2016. Sample size - Fifty-one patients in reproductive age group (18–47 years) who were diagnosed with endometriosis on diagnostic laparoscopy were included. Methods - FSD was assessed with a detailed 19-item female sexual function index questionnaire. All six domains of sexual dysfunction, i.e., desire, arousal, lubrication, orgasm, satisfaction, and pain were studied. Exclusion - Patients with other gynecological, medical or surgical history were excluded. RESULTS: Out of 51 patients with endometriosis, 47.06% of patients had sexual dysfunction. With the increase in staging of endometriosis, sexual dysfunction prevalence is also rising. FSD was 100% in patients with severe endometriosis as compared to 33.33% in minimal endometriosis. CONCLUSION: Every individual deserves good sexual life. The sexual dysfunction associated with endometriosis should also be taken into consideration while managing these patients. PMID:28216913

  2. Body Image and the Female Adolescent Oncology Patient.

    PubMed

    Burg, Alison Joy

    2016-01-01

    Female adolescent oncology patients undergo many physical changes throughout treatment that have challenging psychological, emotional, and social implications. Body image for this population is a subject that tends to be overlooked in the midst of the cancer experience. This article will examine the complex concept of body image and discuss why female adolescent patients are at such high risk for negative body image. Assessment and care strategies are needed to foster a positive body image, resiliency, and overall well-being. Although survivorship studies may offer insightful information about the effects of the cancer journey on long-term body image, focus should be on prevention and holistic care as part of the treatment itself. The health care team, especially nursing professionals, should acknowledge, recognize, and address this vital issue as a critical part of oncology care.

  3. Female sexual dysfunction and hormonal status in multiple sclerosis patients.

    PubMed

    Lombardi, Giuseppe; Celso, Maria; Bartelli, Mario; Cilotti, Antonio; Del Popolo, Giulio

    2011-04-01

    Literature holds no information on a correlation between blood hormonal levels, in particular sex hormones and the sexual response of women with multiple sclerosis (MS). To investigate a possible correlation between hormonal status and the sexual response of females with MS. The Female Sexual Function Index (FSFI) questionnaire was used to determine sexual dysfunctions (SDs). Methods for measuring blood hormones were chemiluminescence immunoassay, electrochemiluminescence immunoassay, enzyme immunoassay, and radioimmunoassay. During the screening phase, 55 women of reproductive age were recruited and completed the FSFI. In the first phase of the study females underwent a hematic hormonal evaluation on the third day of their menstrual cycle. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstenedione, 17[alpha]-hydroxyprogesterone, total and free testosterone, 17 beta estradiol, inhibin and sex hormone binding globulin (SHBG), and thyroid hormones (fT3 and fT4) were checked. On the day 20-21 into their menstrual cycle the progesterone hematic value was noted. Patients with amenorrhea had all hormones tested once with a random blood drawing. After a 3-month period patients began phase 2, completing the FSFI again. The same blood hormones were investigated. Fifty-four females completed the study. Thirty-one continued to manifest at least one SD: desire (57.4%) was the most common. Overall, 36.4% showed abnormal hormonal alterations. The most frequent was 40% for 17 beta-estradiol. None of the FSFI domains, including the total score, revealed any statistically significant correlation to the hormones investigated. No statistically significant clinical predictive factors for blood hormone abnormalities were detected; comparing females with and without SD, P = 0.250 using chi-squared test was reached. Notable percentages of blood hormonal

  4. Male and female transsexualism: the Danish experience with 37 patients.

    PubMed

    Sørensen, T; Hertoft, P

    1982-04-01

    Since the first sex-reassignment operation in Denmark at the Rigshospitalet in 1951, a total of 37 patients, 29 males and 8 females, have had sex-modifying surgery and a change in legal status. In our experience a basic insecure gender identity is a predominant trait in transsexuals, dating back to earliest childhood. This insecurity and a concomitant anxiety are overcome differently by the two transsexual sexes. In male transsexualism, the most outstanding characteristic is a narcissistic withdrawal to a condition marked by submission and pseudofeminity. Anxiety and insecurity are basic to the gender dysphoria but are subdued by means of fantasy escape and gratification in aestheticized ego-ideals with suppression of aggressive and sexual feelings. This results in the often observed pseudofeminity in the male transsexual. A core group of transsexual males are marked by a persistent pseudofeminine narcissism. They have stable ego strength, are agenital in sexual attitude, and have an intact sense of reality. This group is expected to remain so after sex reassignment. The transsexual female assumes a narcissistic, phallic attitude displaying outer activities and caricatured masculine manners in an attempt to subdue her insecurity. Examples are given of the characteristic splitting of these persons' phenomenological ego-experiences and how different their reality testing is from that of psychotic persons with a desire for sex change. Transsexual females are much more sexually active than transsexual males. We find a closer connection between female homosexuality and transsexualism than between male homosexuality and transsexualism.

  5. Hypovitaminosis D in female patients with chronic low back pain.

    PubMed

    Lotfi, Ahmed; Abdel-Nasser, Ahmed M; Hamdy, Ahmed; Omran, Ahmed A; El-Rehany, Mahmoud A

    2007-11-01

    Chronic low back pain (LBP) is an extremely common problem in practice, where it is often labeled idiopathic. No sufficient studies have been conducted to analyze the contribution of hypovitaminosis D to the etiology of chronic LBP in populations wherein vitamin D deficiency is endemic. The present study was, therefore, carried out to examine hypovitaminosis D and its determinants in female patients with chronic LBP during the childbearing period. Sixty female patients complaining of LBP lasting more than 3 months were clinically studied rheumatologically and neurologically. Questionnaires and indices quantifying risk factors associated with vitamin D deficiency were utilized. Biochemical assays of serum calcium, phosphorus, alkaline phosphatase (ALP), parathormone (PTH), and 25-hydroxyvitamin D (25 OHD) were performed and compared to those of 20 matched healthy controls. The determinants of vitamin D levels in patients were examined by stepwise regression. Patients with LBP had significantly lower 25 OHD levels (p < 0.05) and significantly higher PTH (p < 0.05) and ALP (p < 0.001) than controls, although there were no significant group differences in calcium and phosphorus. Hypovitaminosis D (25 OHD < 40 ng/ml) was found in 49/60 patients (81%) and 12/20 (60%) of controls, with an odds ratio of 2.97. Although many risk factors related to sun exposure, clothing, diet, and pregnancy were significantly correlated with vitamin D levels in patients, only limited duration of sun exposure, contributing 55% to the variance of 25 OHD, limited areas of skin exposed (13%), and increased number of pregnancies (2%), were significant determinants of vitamin D levels in patients. Despite the sunny climate, hypovitaminosis D is prevalent among Egyptian women in the childbearing period, especially those presenting with chronic LBP, where it is associated with hyperphosphatasia and hyperparathyroidism, without alterations in serum calcium. The major determinant of hypovitaminosis D

  6. Reduced glucosylceramide in the mouse model of Fabry disease: correction by successful enzyme replacement therapy.

    PubMed

    Quinta, Rui; Rodrigues, Daniel; Assunção, Marisa; Macedo, Maria Fatima; Azevedo, Olga; Cunha, Damião; Oliveira, Pedro; Sá Miranda, Maria Clara

    2014-02-15

    Fabry disease is an X-linked lysosomal storage disease (LSD) caused by deficient activity of α-Galactosidase A (α-Gal A). As a result, glycosphingolipids, mainly globotriaosylceramide (Gb3), progressively accumulate in body fluids and tissues. Studies aiming at the identification of secondary lipid alterations in Fabry disease may be potentially useful for the monitorization of the response to enzyme replacement therapy (ERT) and development of future therapies. The focus of this study was to evaluate if α-Gal A deficiency has an effect on two key groups of molecules of sphingolipids metabolism: glucosylceramides (GlucCers) and ceramides (Cers). Studies performed in a mouse model of Fabry disease showed reduced level of GlucCer and normal level of Cer in plasma, liver, spleen, kidney and heart. Moreover, analysis of GlucCer isoforms in Fabry knockout mice showed that GlucCer isoforms are unequally reduced in different tissues of these animals. ERT had a specific effect on the liver's GlucCer levels of Fabry knockout mice, increasing hepatic GlucCer to the levels observed in wild type mice. In contrast to Fabry knockout mice, plasma of Fabry patients had normal GlucCer and Cer but an increased GlucCer/Cer ratio. This alteration showed a positive correlation with plasma globotriaosylsphingosine (lyso-Gb3) concentration. In conclusion, this work reveals novel secondary lipid imbalances caused by α-Gal A deficiency.

  7. Cardiac device implantation in Fabry disease: A retrospective monocentric study.

    PubMed

    Sené, Thomas; Lidove, Olivier; Sebbah, Joel; Darondel, Jean-Marc; Picard, Hervé; Aaron, Laurent; Fain, Olivier; Zenone, Thierry; Joly, Dominique; Charron, Philippe; Ziza, Jean-Marc

    2016-10-01

    The incidence and predictive factors of arrhythmias and/or conduction abnormalities (ACAs) requiring cardiac device (CD) implantation are poorly characterized in Fabry disease (FD). The aim of our retrospective study was to determine the prevalence, incidence, and factors associated with ACA requiring CD implantation in a monocentric cohort of patients with confirmed FD who were followed up in a department of internal medicine and reference center for FD.Forty-nine patients (20M, 29F) were included. Nine patients (4M, 5F; 18%) had at least one episode of ACA leading to device therapy. Six patients (4M/2F) required a pacemaker (PM) for sinus node dysfunction (n = 4) or atrioventricular disease (n = 2). One female patient required an internal cardioverter-defibrillator (ICD) to prevent sudden cardiac death because of nonsustained ventricular tachycardia (nSVT). One female patient required PM-ICD for sinus node dysfunction and nSVT. One patient underwent CD implantation before the diagnosis of FD. The annual rate of CD implantation was estimated at 1.90 per 100 person years. On univariate analysis at the end of the follow-up period, the factors associated with ACAs requiring CD implantation were as follows: delayed diagnosis of FD, delayed initiation of enzyme replacement therapy, age at the last follow-up visit, and severe multiorgan phenotype (hypertrophic cardiomyopathy, chronic kidney disease, and/or sensorineural hearing loss). On multivariate analysis, age at diagnosis of FD and age at the last follow-up visit were independently associated with an increased risk of ACAs requiring CD (P < 0.05).Considering the high frequency of ACAs requiring CD implantation and the risk of sudden death in patients with FD, regular monitoring is mandatory, especially in patients with a late diagnosis of FD and/or with a severe phenotype. Regular Holter ECGs, therapeutic education of patients, and deliverance of an emergency card including a phenotype summary are

  8. Anderson-Fabry cardiomyopathy: prevalence, pathophysiology, diagnosis and treatment.

    PubMed

    Putko, Brendan N; Wen, Kevin; Thompson, Richard B; Mullen, John; Shanks, Miriam; Yogasundaram, Haran; Sergi, Consolato; Oudit, Gavin Y

    2015-03-01

    Anderson-Fabry disease (AFD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide in tissues due to a deficiency in the enzyme α-galactosidase A (α-Gal A). Anderson-Fabry cardiomyopathy is characterized by structural, valvular, vascular and conduction abnormalities, and is now the most common cause of mortality in patients with AFD. Large-scale metabolic and genetic screening studies have revealed AFD to be prevalent in populations of diverse ethnic origins, and the variant form of AFD represents an unrecognized health burden. Anderson-Fabry disease is an X-linked disorder, and genetic testing is critical for the diagnosis of AFD in women. Echocardiography with strain imaging and cardiac magnetic resonance imaging using late enhancement and T1 mapping are important imaging tools. The current therapy for AFD is enzyme replacement therapy (ERT), which can reverse or prevent AFD progression, while gene therapy and the use of molecular chaperones represent promising novel therapies for AFD. Anderson-Fabry cardiomyopathy is an important and potentially reversible cause of heart failure that involves LVH, increased susceptibility to arrhythmias and valvular regurgitation. Genetic testing and cardiac MRI are important diagnostic tools, and AFD cardiomyopathy is treatable if ERT is introduced early.

  9. Fabry Disease Presenting with Hypertrophic Cardiomyopathy and Tricuspid Regurgitation

    PubMed Central

    Cho, Sang-Cheol; Yoo, Han-Wook; Lee, Jae Won; Jang, Jeong Yoon; Heo, Ran

    2016-01-01

    A 71-year-old female who was diagnosed with nonobstructive hypertrophic cardiomyopathy since 1999 presented with dyspnea and severe edema on both legs. For the management of her symptom, cardiac surgery including tricuspid annuloplasty, Maze operation and right atrial reduction plasty was performed. During follow-up after cardiac surgery, a plasma α-galactosidase activity was checked for the screening of Fabry disease and the result was around lower normal limit. DNA analysis was implemented for confirmation and it revealed a heterozygote α-galactosidase mutation at exon 6 [c.901C>T (p.Arg301Ter)]. This case suggests that Fabry disease might be easily undetected, and clinical suspicion is critical. PMID:28090261

  10. Prevalence of Raynaud Phenomenon and Nailfold Capillaroscopic Abnormalities in Fabry Disease

    PubMed Central

    Deshayes, Samuel; Auboire, Laurent; Jaussaud, Roland; Lidove, Olivier; Parienti, Jean-Jacques; Triclin, Nathalie; Imbert, Bernard; Bienvenu, Boris; Aouba, Achille

    2015-01-01

    Abstract Fabry disease (FD) is a lysosomal disorder leading to progressive systemic involvement, including microvascular damage that leads to neurological and cardiovascular disorders. We hypothesize that the latter could be documented at an early stage by performing a microcirculation study with nailfold capillaroscopy and evaluation of Raynaud phenomenon. The objective was to measure the prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in FD. This cross-sectional study included a standardized questionnaire and a nailfold capillaroscopy that assessed previously reported patterns in FD (dystrophic and giant capillaries, avascular fields, irregular architecture, dilatation and density of capillaries, hemorrhage), and was conducted on 32 Fabry patients and 39 controls. Capillaroscopic photographs were reviewed by 2 independent blinded investigators. Twelve Fabry patients (38%) suffered from Raynaud phenomenon, 5 were males (ie, 50% of male Fabry patients), compared with 2 controls (13%) (P < 0.001), of whom none were males (P < 0.001). Raynaud phenomenon was concomitant or before the occurrence of pain in the extremities in 42% of Fabry patients. More ramified capillaries were significantly observed in Fabry patients (12/32, 38%) than in controls (5/39, 13%, P = 0.016). Secondary Raynaud phenomenon should lead to screening for FD, especially in men. By extension, in high-risk populations for FD, the presence of Raynaud phenomenon and ramified capillaries should be assessed. PMID:25997047

  11. Prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in Fabry disease: a cross-sectional study.

    PubMed

    Deshayes, Samuel; Auboire, Laurent; Jaussaud, Roland; Lidove, Olivier; Parienti, Jean-Jacques; Triclin, Nathalie; Imbert, Bernard; Bienvenu, Boris; Aouba, Achille

    2015-05-01

    Fabry disease (FD) is a lysosomal disorder leading to progressive systemic involvement, including microvascular damage that leads to neurological and cardiovascular disorders. We hypothesize that the latter could be documented at an early stage by performing a microcirculation study with nailfold capillaroscopy and evaluation of Raynaud phenomenon.The objective was to measure the prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in FD.This cross-sectional study included a standardized questionnaire and a nailfold capillaroscopy that assessed previously reported patterns in FD (dystrophic and giant capillaries, avascular fields, irregular architecture, dilatation and density of capillaries, hemorrhage), and was conducted on 32 Fabry patients and 39 controls. Capillaroscopic photographs were reviewed by 2 independent blinded investigators.Twelve Fabry patients (38%) suffered from Raynaud phenomenon, 5 were males (ie, 50% of male Fabry patients), compared with 2 controls (13%) (P < 0.001), of whom none were males (P < 0.001). Raynaud phenomenon was concomitant or before the occurrence of pain in the extremities in 42% of Fabry patients.More ramified capillaries were significantly observed in Fabry patients (12/32, 38%) than in controls (5/39, 13%, P = 0.016).Secondary Raynaud phenomenon should lead to screening for FD, especially in men. By extension, in high-risk populations for FD, the presence of Raynaud phenomenon and ramified capillaries should be assessed.

  12. Chronic paracoccidioidomycosis in a female patient in Austria.

    PubMed

    Mayr, A; Kirchmair, M; Rainer, J; Rossi, R; Kreczy, A; Tintelnot, K; Dierich, M P; Lass-Flörl, C

    2004-12-01

    Presented here is a case of chronic paracoccidioidomycosis that occurred in a Cuban female living in Austria and was first misdiagnosed as tuberculosis. The clinical picture was one of progressive pulmonary insufficiency with fever, weight loss and productive cough. Since antituberculous therapy was started but did not achieve a long-term clinical response, an intensive diagnostic work-up was performed. Paracoccidioides brasiliensis was then diagnosed by histopathology, serology, microbiology and molecular identification. Antifungal therapy was commenced immediately with amphotericin B (1 mg/kg/day) for 10 days, followed by voriconazole (200 mg/day po) for at least 3 months, and the lesions disappeared almost completely. This report presents the first published case of imported paracoccidioidomycosis in a female patient in Austria.

  13. Female sexual dysfunction in patients with substance-related disorders

    PubMed Central

    Diehl, Alessandra; da Silva, Rosiane Lopes; Laranjeira, Ronaldo

    2013-01-01

    OBJECTIVE: To estimate the prevalence of female sexual dysfunction symptoms and the associated risk factors in a sample of patients with substance-related disorders admitted to a specialized in-patient care unit. METHODS: This study used a cross-section design, with eight months of data collection, conducted with substance-dependent women using structured questionnaires to collect socio-demographic data and identify their drug of choice. The Drug Abuse Screening Test, Short Alcohol Dependence Data questionnaire, Fagerström Test for Nicotine Dependence, and Arizona Sexual Experience Scale were also administered. RESULTS: The sample consisted of 105 women who had a mean age of 34.8 years (SD = 12.1, range = 18-65) and were predominantly heterosexual (74.3%), single (47.6%), Caucasian (50.5%), catholic (36.2%), and educated only to the level of primary education (40%), with a monthly family income of up to one minimum salary (37.5%). In 42.9% of the patients, crack was the drug of choice; 47.6% of the sample qualified for the Drug Abuse Screening Test (substantial problems related to drugs), 43.8% exhibited Short Alcohol Dependence Data (moderate or severe dependency), 47.6% exhibited Fagerström Test for Nicotine Dependence (high or very high nicotine dependence). The prevalence of sexual dysfunction symptoms was 34.2% (95% CI = [25.3, 44.1]), and a high level of nicotine dependence and low income increased the chances of having sexual dysfunction by 2.72-fold and 2.54 fold, respectively. An association was also observed between female sexual dysfunction symptoms and schooling and levels of drug dependence. CONCLUSIONS: Female sexual dysfunction symptoms were common among this sample and primarily associated with high levels of nicotine use. PMID:23525317

  14. Female sexual dysfunction in patients with substance-related disorders.

    PubMed

    Diehl, Alessandra; Silva, Rosiane Lopes da; Laranjeira, Ronaldo

    2013-01-01

    To estimate the prevalence of female sexual dysfunction symptoms and the associated risk factors in a sample of patients with substance-related disorders admitted to a specialized in-patient care unit. This study used a cross-section design, with eight months of data collection, conducted with substance-dependent women using structured questionnaires to collect socio-demographic data and identify their drug of choice. The Drug Abuse Screening Test, Short Alcohol Dependence Data questionnaire, Fagerstrom Test for Nicotine Dependence, and Arizona Sexual Experience Scale were also administered. The sample consisted of 105 women who had a mean age of 34.8 years (SD = 12.1, range = 18-65) and were predominantly heterosexual (74.3%), single (47.6%), Caucasian (50.5%), catholic (36.2%), and educated only to the level of primary education (40%), with a monthly family income of up to one minimum salary (37.5%). In 42.9% of the patients, crack was the drug of choice; 47.6% of the sample qualified for the Drug Abuse Screening Test (substantial problems related to drugs), 43.8% exhibited Short Alcohol Dependence Data (moderate or severe dependency), 47.6% exhibited Fagerstrom Test for Nicotine Dependence (high or very high nicotine dependence). The prevalence of sexual dysfunction symptoms was 34.2% (95% CI = [25.3, 44.1]), and a high level of nicotine dependence and low income increased the chances of having sexual dysfunction by 2.72-fold and 2.54 fold, respectively. An association was also observed between female sexual dysfunction symptoms and schooling and levels of drug dependence. Female sexual dysfunction symptoms were common among this sample and primarily associated with high levels of nicotine use.

  15. Height velocity curves in female patients with idiopathic scoliosis.

    PubMed

    Chazono, Masaaki; Soshi, Sigeru; Kida, Yoshikuni; Hashimoto, Kurando; Inoue, Takeshi; Nakamura, Yousuke; Shinohara, Akira; Marumo, Keishi; Kono, Katsuki; Suzuki, Nobumasa

    2012-01-01

    Following identification of peak height velocity (PHV) by a recent study as a possible prognostic factor for curve progression in patients with idiopathic scoliosis (IS), the aim of this study was to investigate PHV curves in Japanese female patients with IS. The study subjects were 20 skeletally immature IS patients who were followed until maturity. The mean age and the mean pubertal status at the initial visit were 9.8 years and 24 months before menarche, respectively, with a follow-up period of 5.2 years. Height measurements were recorded at each visit, and HV was calculated as the change in height (cm) divided by the time interval (yr.) between visits of 6 to 12 months. The PHV, age at PHV (APHV), height at PHV (HPHV), and final height (FH) were determined. Patient HV curves were plotted using their HV data, and growth periods (GPs) were calculated from the curves. PHVs and GPs of study patients were compared to standard data from unaffected girls. The median values and interquartile ranges in PHV, APHV, HPHV, and FH were 8.5 cm/yr. (7.9-9.7), 11.8 yr. (11.2-12.1), 153.2 cm (150.1-155.8), and 160.1 cm (157.4-162.4), respectively. The median GP was 27 months. The PHV and GP values in IS female patients were higher and shorter than those in unaffected girls. These findings indicate that the patterns of height velocity curves in IS patients are different from those in unaffected girls, suggesting that curve progression in IS patients is associated with the magnitude of PHV and duration of GP. Recently, we have developed an HV reader to easily and quickly identify the present HV in patients with scoliosis, applicable for the clinical setting or school screening. We conclude that risk assessments of curve progression in patients with IS should include HV along with measures of skeletal maturity such as the Risser sign and/or digital skeletal age using hand X-rays.

  16. Cognitive functioning in female patients with 21-hydroxylase deficiency.

    PubMed

    Dittmann, R W; Kappes, M H; Kappes, M E

    1993-01-01

    The cognitive functioning of 27 female patients with congenital adrenal hyperplasia (CAH) (aged 11-41 yrs) and 13 of their healthy sisters (13-31 yrs) was compared using short versions of age-appropriate Wechsler scales. In contrast to other studies, neither a higher than average IQ level for CAH patients (mean: 99.0) nor for their sisters (97.7) was found. Unexpectedly, and in contrast to other reports, the subgroup of salt-wasting (SW) patients>16 yrs (N=6; mean score: 111.5) differed from their sisters as well as from simple-virilizing (SV) patients in "full IQ" (p<0.05) and subtest scorings for "Information", "Similarities", and "Picture Completion" (p<0.05-<0.10). SW patients displayed "more masculine" behaviour (vs. SV patients and sisters) which, in turn, was related to differential prenatal hormonal influences. No clear-cut relationships between IQ/cognitive (subtest) findings and gender-role behaviour were found.

  17. Inhaled corticosteroids can reduce osteoporosis in female patients with COPD

    PubMed Central

    Liu, Shih-Feng; Kuo, Ho-Chang; Liu, Guan-Heng; Ho, Shu-Chen; Chang, Huang-Chih; Huang, Hung-Tu; Chen, Yu-Mu; Huang, Kuo-Tung; Chen, Kuan-Yi; Fang, Wen-Feng; Lin, Meng-Chih

    2016-01-01

    Background Whether the use of inhaled corticosteroids (ICSs) in patients with COPD can protect from osteoporosis remains undetermined. The aim of this study is to assess the incidence of osteoporosis in patients with COPD with ICS use and without. Patients and methods This is a retrospective cohort and population-based study in which we extracted newly diagnosed female patients with COPD between 1997 and 2009 from Taiwan’s National Health Insurance (TNHI) database between 1996 and 2011 (International Classification of Diseases, Ninth Revision – Clinical Modification [ICD-9-CM] 491, 492, 496). The patients with COPD were defined by the presence of two or more diagnostic codes for COPD within 12 months on either inpatient or outpatient service claims submitted to TNHI. Patients were excluded if they were younger than 40 years or if osteoporosis had been diagnosed prior to the diagnosis of COPD and cases of asthma (ICD-9 CM code 493.X) before the index date. These enrolled patients were followed up till 2011, and the incidence of osteoporosis was determined. The Cox proportional hazards regression model was also used to estimate hazard ratios (HRs) for incidences of lung cancer. Results Totally, 10,723 patients with COPD, including ICS users (n=812) and nonusers (n=9,911), were enrolled. The incidence rate of osteoporosis per 100,000 person years is 4,395 in nonusers and 2,709 in ICS users (HR: 0.73, 95% confidence interval [CI]: 0.63–084). The higher ICS dose is associated with lower risk of osteoporosis (0 mg to ≤20 mg, HR: 0.84, 95% CI: 0.69–1.04; >20 mg to ≤60 mg, HR: 0.78, 95% CI: 0.59–1.04; and >60 mg, HR: 0.72, 95% CI: 0.55–0.96; P for trend =0.0023) after adjusting for age, income, and medications. The cumulative osteoporosis probability significantly decreased among the ICS users when compared with the nonusers (P<0.001). Conclusion Female patients with COPD using ICS have a dose–response protective effect for osteoporosis. PMID:27478374

  18. The Impact of Fabry Disease on Reproductive Fitness.

    PubMed

    Laney, Dawn A; Clarke, Virginia; Foley, Allison; Hall, Eric W; Gillespie, Scott E; Holida, Myrl; Simmons, Morgan; Wadley, Alexandrea

    2017-03-22

    Fabry disease (FD) is a pan-ethnic, X-linked, progressive lysosomal storage disorder caused by pathogenic mutations in the GLA gene. Published case reports and abstracts suggest that decreased reproductive fitness may occur in males with FD. In order to understand the impact of FD on reproductive fitness and increase the accuracy of reproductive genetic counseling, this study examines a large, multi-centered population of individuals with FD to determine if males have reduced reproductive fitness. Study data were collected on 376 patients through two, gender-specific surveys distributed across the United States and Canada. The number of biological live-born children among individuals with FD was compared to statistics from the general population. Information was also collected on reduced sperm count, depression, pain, use of assisted reproductive technology, and reproductive choice. On average, females affected by FD had more biological live-born children (1.8) than males affected by FD (1.1). However, males affected by FD had an increased mean number of biological children (1.1) compared to the mean number of biological children fathered by men in the United States (0.9). Sixteen of the 134 males with FD reported oligospermia, which suggests that an infertility work up may be indicated for males having difficulty impregnating their partners. In our large multicenter sample, males and females with FD do not exhibit reduced reproductive fitness; on average they have more biological children than the general population in the United States. This information should assist clinicians in providing accurate reproductive genetic counseling and treatment for individuals with FD.

  19. Caring for female patients: The experiences of male nurses.

    PubMed

    Keogh, Brian; Gleeson, Madeline

    This article presents the results of two small qualitative studies, which examined the experiences of six male registered psychiatric nurses (RPN) and five male registered general nurses (RGN) when caring for patients of the opposite sex. Semi-structured interviews were used to collect the data. The focus of the interviews was an attempt to describe the male nurses' experiences of caring for women with a particular emphasis on interventions that involved physical touch. Themes were generated from both studies and the common themes are presented here. Male nurses in this study were often apprehensive about using physical touch and they used coping strategies in response to their fears of being accused of using touch inappropriately. Several factors also influenced the male nurses when using physical touch as an intervention. These findings suggest that learning about caring for female patients needs to be included in the undergraduate curriculum and that further research on the experience of men as nurses is required.

  20. Peripheral blood methylation profiling of female Crohn's disease patients.

    PubMed

    Li Yim, Andrew Y F; Duijvis, Nicolette W; Zhao, Jing; de Jonge, Wouter J; D'Haens, Geert R A M; Mannens, Marcel M A M; Mul, Adri N P M; Te Velde, Anje A; Henneman, Peter

    2016-01-01

    Crohn's disease (CD) is a chronic inflammatory disorder belonging to the inflammatory bowel diseases (IBD). CD affects distinct parts of the gastrointestinal tract, leading to symptoms including diarrhea, fever, abdominal pain, weight loss, and anemia. The aim of this study was to assess whether the DNA methylome of peripheral blood cells can be associated with CD in women. Samples were obtained from 18 female patients with histologically confirmed ileal or ileocolic CD and 25 healthy age- and gender-matched controls (mean age and standard deviation: 30.5 ± 6.5 years for both groups). Genome-wide DNA methylation was determined using the Illumina HumanMethylation 450k BeadChip. Our analysis implicated 4287 differentially methylated positions (DMPs; corrected p < 0.05) that are associated to 2715 unique genes. Gene ontology enrichment analysis revealed significant enrichment of our DMPs in immune response processes and inflammatory pathways. Of the 4287 DMPs, 32 DMPs were located on chromosome X with several hits for MIR223 and PABPC5. Comparison with previously performed (epi)genome-wide studies revealed that we replicated 33 IBD-associated genes. In addition to DMPs, we found eight differentially methylated regions (DMRs). CD patients display a characteristic DNA methylation landscape, with the differentially methylated genes being implicated in immune response. Additionally, DMPs were found on chromosome X suggesting X-linked manifestations of CD that could be associated with female-specific symptoms.

  1. A renal variant of Fabry disease: A case with a novel Gal A hemizygote mutation

    PubMed Central

    H. Mukdsi, Jorge; Gutiérrez, Silvina; Barrón, Belén; Novoa, Pablo; Fernández, Segundo; de Diller, Ana B; I. Torres, Alicia; Formica Jr., Richard N; Orías, Marcelo

    2012-01-01

    Background Fabry disease is caused by an X-linked recessive inborn error of glycosphingolipid metabolism with deficient activity of a lysosomal enzyme, alpha-galactosidase A (α-GalA). Case Presentation A 46 year-old man with progressive kidney disease showed on kidney biopsy electron microscopic evidence of Fabry disease. The patient had no systemic manifestations of Fabry disease, despite residual α-GalA activity, therefore genetic testing was done by direct DNA sequencing, demonstrating a new GAL A gene mutation (C174G-exon 3). After three years of enzyme replacement therapy (agalsidase beta) treatment, a second biopsy was done. Although there was demonstrable clearance of intracellular inclusions, remarkable podocyte activation was evident. Conclusions This report represents an unusual renal variant of Fabry disease and provides histologic data on long-term follow up after enzyme replacement therapy. PMID:24475416

  2. [Subclinical sensorineural hearing loss in female patients with rheumatoid arthritis].

    PubMed

    Treviño-González, José Luis; Villegas-González, Mario Jesús; Muñoz-Maldonado, Gerardo Enrique; Montero-Cantu, Carlos Alberto; Nava-Zavala, Arnulfo Hernán; Garza-Elizondo, Mario Alberto

    2015-01-01

    The rheumatoid arthritis is a clinical entity capable to cause hearing impairment that can be diagnosed promptly with high frequencies audiometry. To detect subclinical sensorineural hearing loss in patients with rheumatoid arthritis. Cross-sectional study on patients with rheumatoid arthritis performing high frequency audiometry 125Hz to 16,000Hz and tympanometry. The results were correlated with markers of disease activity and response to therapy. High frequency audiometry was performed in 117 female patients aged from 19 to 65 years. Sensorineural hearing loss was observed at a sensitivity of pure tones from 125 to 8,000 Hz in 43.59%, a tone threshold of 10,000 to 16,000Hz in 94.02% patients in the right ear and in 95.73% in the left ear. Hearing was normal in 8 (6.84%) patients. Hearing loss was observed in 109 (93.16%), and was asymmetric in 36 (30.77%), symmetric in 73 (62.37%), bilateral in 107 (91.45%), unilateral in 2 (1.71%), and no conduction and/or mixed hearing loss was encountered. Eight (6.83%) patients presented vertigo, 24 (20.51%) tinnitus. Tympanogram type A presented in 88.90% in the right ear and 91.46% in the left ear, with 5.98 to 10.25% type As. Stapedius reflex was present in 75.3 to 85.2%. Speech discrimination in the left ear was significantly different (p = 0.02)in the group older than 50 years. No association was found regarding markers of disease activity, but there was an association with the onset of rheumatoid arthritis disease. Patients with rheumatoid arthritis had a high prevalence of sensorineural hearing loss for high and very high frequencies. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  3. Pituitary function and morphology in Fabry disease.

    PubMed

    Maione, Luigi; Tortora, Fabio; Modica, Roberta; Ramundo, Valeria; Riccio, Eleonora; Daniele, Aurora; Belfiore, Maria Paola; Colao, Annamaria; Pisani, Antonio; Faggiano, Antongiulio

    2015-11-01

    Endocrine abnormalities are known to affect patients with Fabry disease (FD). Pituitary gland theoretically represents an ideal target for FD because of high vascularization and low proliferation rate. We explored pituitary morphology and function in a cohort of FD patients through a prospectic, monocentric study at an Academic Tertiary Center. The study population included 28 FD patients and 42 sex and age-matched normal subjects. The protocol included a contrast enhancement pituitary MRI, the assessment of pituitary hormones, anti-pituitary, and anti-hypothalamus antibodies. At pituitary MRI, an empty sella was found in 11 (39%) FD patients, and in 2 (5%) controls (p < 0.001). Pituitary volume was significantly smaller in FD than in controls (p < 0.001). Determinants of pituitary volume were age and alpha-galactosidase enzyme activity. Both parameters resulted independently correlated at multivariate analysis. Pituitary function was substantially preserved in FD patients. Empty sella is a common finding in patients with FD. The major prevalence in the elderly supports the hypothesis of a progressive pituitary shrinkage overtime. Pituitary function seems not to be impaired in FD. An endocrine workup with pituitary hormone assessment should be periodically performed in FD patients, who are already at risk of cardiovascular complications.

  4. Multiplex Fabry-Perot interferometer

    NASA Technical Reports Server (NTRS)

    Hays, Paul B.; Snell, Hilary E.

    1991-01-01

    Attention is given to a Fabry-Perot interferometer (FPI) technique in which one of the etalon plates is moved over a large optical distance while the other remains fixed, thus exploiting the multiplex advantage of the instrument. This technique involves the application of Fourier-transform spectrometer to the multiple harmonics passing through the FPI etalon. It is shown that the multiplex FPI acts as several Michelson interferometers working at the same time, over the same spectral interval, and at different spectral resolutions. A high spectral resolution has been obtained over a large wavenumber interval, while the advantage of a reasonable scan length has been retained.

  5. Multiplex Fabry-Perot interferometer

    NASA Technical Reports Server (NTRS)

    Hays, Paul B.; Snell, Hilary E.

    1991-01-01

    Attention is given to a Fabry-Perot interferometer (FPI) technique in which one of the etalon plates is moved over a large optical distance while the other remains fixed, thus exploiting the multiplex advantage of the instrument. This technique involves the application of Fourier-transform spectrometer to the multiple harmonics passing through the FPI etalon. It is shown that the multiplex FPI acts as several Michelson interferometers working at the same time, over the same spectral interval, and at different spectral resolutions. A high spectral resolution has been obtained over a large wavenumber interval, while the advantage of a reasonable scan length has been retained.

  6. Left Ventricular Geometry and Blood Pressure as Predictors of Adverse Progression of Fabry Cardiomyopathy

    PubMed Central

    Krämer, Johannes; Bijnens, Bart; Störk, Stefan; Ritter, Christian O.; Liu, Dan; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2015-01-01

    Background In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated. Methods In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed. Results Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05). Conclusions LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy. PMID:26600044

  7. Body images of patients with anorexia nervosa, bulimia nervosa and female control subjects: a comparison with male ideals of female attractiveness.

    PubMed

    Benninghoven, Dieter; Raykowski, Lena; Solzbacher, Svenja; Kunzendorf, Sebastian; Jantschek, Günter

    2007-03-01

    Body images of female patients with anorexia nervosa and bulimia nervosa were assessed against females without eating disorders and compared with male ideals of female attractiveness. A computer program was applied to examine body images of 62 patients with anorexia nervosa, 45 patients with bulimia nervosa, and 40 female and 39 male control subjects. Body size overestimation was most distinct in the two patient groups. Self-ideal discrepancy was highest in bulimia nervosa. Estimation of the society's ideal female body in all three female groups did not differ from men's perception of the most attractive female body. Congruence of ideals of female attractiveness in patients, female, and male control subjects and described differences between patients and female controls support the theory that body image disturbance is a problem of processing self-referential information regarding body image rather than a problem of processing body image related information per se.

  8. Female Patients Require a Higher Propofol Infusion Rate for Sedation.

    PubMed

    Maeda, Shigeru; Tomoyasu, Yumiko; Higuchi, Hitoshi; Honda, Yuka; Ishii-Maruhama, Minako; Miyawaki, Takuya

    2016-01-01

    Sedation may minimize physiologic and behavioral stress responses. In our facility, the infusion rate of propofol is adjusted according to the bispectral index (BIS) in all cases of implant-related surgery; multivariate analysis of retrospective data enabled us to extract independent factors that affect the dose of propofol in sedation that are considered useful indicators for achieving adequate sedation. The study population comprised all patients undergoing implant-related surgery under intravenous sedation in Okayama University Hospital from April 2009 to March 2013. The infusion rate of propofol was adjusted to maintain the BIS value at 70-80. The outcome was the average infusion rate of propofol, and potential predictor variables were age, sex, body weight, treatment time, and amount of midazolam. Independent variables that affected the average infusion rate of propofol were extracted with multiple regression analysis. One hundred twenty-five subjects were enrolled. In the multiple regression analysis, female sex was shown to be significantly associated with a higher average infusion rate of propofol. Females may require a higher infusion rate of propofol than males to achieve adequate sedation while undergoing implant-related surgery.

  9. Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy.

    PubMed

    Godel, Tim; Bäumer, Philipp; Pham, Mirko; Köhn, Anja; Muschol, Nicole; Kronlage, Moritz; Kollmer, Jennifer; Heiland, Sabine; Bendszus, Martin; Mautner, Victor-Felix

    2017-09-19

    To evaluate functional and morphometric magnetic resonance neurography of the dorsal root ganglion and peripheral nerve segments in patients with Fabry painful neuropathy. In this prospective study, the lumbosacral dorsal root ganglia and proximal peripheral nerve segments of the lower extremity were examined in 11 male patients with Fabry disease by a standardized 3T magnetic resonance neurography protocol. Volumes of L3 to S2 dorsal root ganglia, perfusion parameters of L5-S1 dorsal root ganglia and the spinal nerve L5, and the cross-sectional area of the proximal sciatic nerve were compared to healthy controls. Dorsal root ganglia of patients with Fabry disease were symmetrically enlarged by 78% (L3), 94% (L4), 122% (L5), 115% (S1), and 119% (S2) (p < 0.001). In addition, permeability of the blood-tissue interface was decreased by 53% (p < 0.001). This finding was most pronounced in the peripheral zone of the dorsal root ganglion containing the cell bodies of the primary sensory neurons (p < 0.001). Spinal nerve permeability showed no difference between patients with Fabry disease and controls (p = 0.7). The sciatic nerve of patients with Fabry disease at the thigh level showed an increase in cross-sectional area by 48% (p < 0.001). Patients with Fabry disease have severely enlarged dorsal root ganglia with dysfunctional perfusion. This may be due to glycolipid accumulation in the dorsal root ganglia mediating direct neurotoxic effects and decreased neuronal blood supply. These alterations were less pronounced in peripheral nerve segments. Thus, the dorsal root ganglion might play a key pathophysiologic role in the development of neuropathy and pain in Fabry disease. © 2017 American Academy of Neurology.

  10. A Nutrition Screening Form for Female Infertility Patients.

    PubMed

    Langley, Susie

    2014-12-01

    A Nutrition Screening Form (NSF) was designed to identify lifestyle risk factors that negatively impact fertility and to provide a descriptive profile of 300 female infertility patients in a private urban infertility clinic. The NSF was mailed to all new patients prior to the initial physician's visit and self-reported data were assessed using specific criteria to determine if a nutrition referral was warranted. This observational study revealed that 43% of the women had a body mass index (BMI) <20 or ≥25 kg/m(2), known risks for infertility. Almost half reported a history of "dieting" and unrealistic weight goals potentially limiting energy and essential nutrients. A high number reported eating disorders, vegetarianism, low fat or low cholesterol diets, and dietary supplement use. Fourteen percent appeared not to supplement with folic acid, 13% rated exercise as "extremely" or "very active", and 28% reported a "high" perceived level of stress. This preliminary research demonstrated that a NSF can be a useful tool to identify nutrition-related lifestyle factors that may negatively impact fertility and identified weight, BMI, diet, exercise, and stress as modifiable risk factors deserving future research. NSF information can help increase awareness among health professionals and patients about the important link between nutrition, fertility, and successful reproductive outcomes.

  11. Cluster Headache: Special Considerations for Treatment of Female Patients of Reproductive Age and Pediatric Patients.

    PubMed

    VanderPluym, Juliana

    2016-01-01

    Cluster headache is a rare disorder that is more common in adult male patients. It has a unique phenotype of unilateral, severe, to very severe headaches lasting 15 to 180 min with ipsilateral autonomic symptoms. Time to correct diagnosis can be protracted. A number of treatment options exist for the standard cluster headache patient, but special considerations must be made for female patients of reproductive age and pediatric patients. The objective of this article is to explore the current literature pertaining to special considerations in cluster headache management, including treatment of pregnant or breastfeeding patients and pediatric patients.

  12. Planetary Fabry-Perot spectroscopy

    NASA Technical Reports Server (NTRS)

    Trauger, J. T.

    1988-01-01

    Application of high spectral resolution, Earth-based Fabry-Perot spectroscopy to the study of planetary atmospheres, for which current topics are outer planet HD and H2 spectra (atmospheric structure, D/H ratio), Mars CO2, CO, O2, and H2O spectra (atomspheric photochemistry), Venus H2O and HDO, associated laboratory spectroscopy (especially H2 overtone bands, HDO) was accomplished. Monochromatic charge coupled device (CCD) imaging photometry of the Jovian nebula, with images taken in rapid sequence among the diagnostic spectral lines of ionized sulfur species, provided self-supporting snapshots of the Jupiter/Io plasma conditions (spatially resolved electron and ion densities and temperatures), covering the post-Voyager period from 1981 and leading up to the Galileo tour in the early 1990s. High spectral resolution Fabry-Perot/charge coupled device (CCD) imaging of comets (OI, CI, and H2O(+) velocity maps and spatial distriubtions), and Io's charge exchanged neutral jet was studied.

  13. Autoantibody studies of female patients with reproductive failure.

    PubMed

    Reimand, K; Talja, I; Metsküla, K; Kadastik, U; Matt, K; Uibo, R

    2001-08-01

    The aim of this study was to investigate the prevalence and character of autoimmune derangements in women with reproductive failure. A total of 108 females (age range 17-43, mean 27.5 years), including 16 with primary menstrual cycle disturbances and polycystic ovaries (PCO), 20 with polycystic ovary syndrome (PCOS), 38 with endometriosis (E), and 34 with chronic anovulation, luteal phase insufficiency, subfertility or unexplained infertility (INF) were investigated. A control group of 392 women was formed from an unselected population sample (age range 17-43, mean 31.0 years). All sera were tested by indirect immunofluorescence method to assess common autoantibodies: nuclear (ANA), smooth muscle (SMA), parietal cell (PCA), thyroid microsomal (TMA), reticulin (ARA), mitochondrial (AMA) and liver/kidney microsomal autoantibodies (LKMA). Enzyme-linked immunosorbent assay was used to detect antibodies against beta2-glycoprotein I (anti-beta 2GPI) and carbonic anhydrase (anti-CA). Our results showed that 40.7% of patients' sera and 14.8% of control sera contained one or more common autoantibodies, ANA and SMA were most frequently detected (difference between two groups P<0.005). Anti-beta 2GPI were found in eight cases (7.4%), including two patients with INF but without other autoantibodies. Anti-CA were revealed in nine cases (8.3%) including patients' PCOS, E and INF. A comparison of patients' clinical data with antibody assay results did not reveal any significant associations. Our results indicate a high prevalence of autoimmune reactions in women with reproductive failure due to the most common causes PCO, PCOS and E as well as in unexplained infertility. This might reflect the propensity to develop autoimmune reactions in such patients, including pathogenic autoimmune reactions to specific target antigens.

  14. Selective arterial distribution of cerebral hyperperfusion in Fabry disease.

    PubMed

    Moore, D F; Herscovitch, P; Schiffmann, R

    2001-07-01

    Fabry disease is an X-linked recessive deficiency of lysosomal alpha-galactosidase A associated with an increased risk of early onset cerebrovascular disease. The disorder is reported to affect the posterior circulation predominantly. This hypothesis was investigated directly by the measurement of regional cerebral blood flow with positron emission tomography (PET). Resting regional cerebral blood flow (rCBF) in 26 hemizygous patients with Fabry disease and 10 control participants was examined using H(2)15O and PET. Statistical parametric mapping (SPM(t), SPM99) and PET images of patients and controls were produced. Significantly increased SPM(t) clusters were then color coded and blended with a coregistered T1 magnetic resonance imaging (MRI) template. Cerebral arterial territory maps were digitized and rescaled. Custom OpenGL and ImageVision Library C++ code was written to allow a first-order affine transformation of the blended SPM(t) and MRI template onto the arterial territory map. The affine transformation was constrained by choosing corresponding cerebral landmark "tie points" between the SPM(t) [symbol: see text] MRI template images and the cerebral arterial territory maps. The data demonstrated that the posterior circulation is the predominant arterial territory with a significantly increased rCBF in Fabry disease. No arterial distribution had a decreased rCBF.

  15. Fabry-Perot interferometry for microplasma diagnostics

    SciTech Connect

    Hojo, H.; Mase, A.

    2006-10-15

    A new method for determining the electron density of a thin plasma by means of Fabry-Perot interferometry is proposed. The interferometer consists of two plasma layers and dielectric material surrounded by two plasma layers. The transmittance of electromagnetic waves across the interferometer is calculated, and Fabry-Perot resonances are demonstrated. It is shown that the electron density can be determined from the measurement of the Fabry-Perot resonance frequencies. This method can also be applied to the measurement of conduction electron density in semiconductor films.

  16. Patient-Centered Mental Health Care for Female Veterans

    PubMed Central

    Kimerling, Rachel; Bastian, Lori A.; Bean-Mayberry, Bevanne A.; Bucossi, Meggan M.; Carney, Diane V.; Goldstein, Karen M.; Phibbs, Ciaran S.; Pomernacki, Alyssa; Sadler, Anne G.; Yano, Elizabeth M.; Frayne, Susan M.

    2016-01-01

    Objective Mental health services for women vary widely across the Veterans Health Administration (VHA) system, without consensus on the need for, or organization of, specialized services for women. Understanding women’s needs and priorities is essential to guide the implementation of patient-centered behavioral health services. Methods In a cross-sectional, multisite survey of female veterans using primary care, potential stakeholders were identified for VHA mental health services by assessing perceived or observed need for mental health services. These stakeholders (N=484) ranked priorities for mental health care among a wide range of possible services. The investigators then quantified the importance of having designated women’s mental health services for each of the mental health services that emerged as key priorities. Results Treatment for depression, pain management, coping with chronic general medical conditions, sleep problems, weight management, and posttraumatic stress disorder (PTSD) emerged as women’s key priorities. Having mental health services specialized for women was rated as extremely important to substantial proportions of women for each of the six prioritized services. Preference for primary care colocation was strongly associated with higher importance ratings for designated women’s mental health services. For specific types of services, race, ethnicity, sexual orientation, PTSD symptoms, and psychiatric comorbidity were also associated with higher importance ratings for designated women’s services. Conclusions Female veterans are a diverse population whose needs and preferences for mental health services vary along demographic and clinical factors. These stakeholder perspectives can help prioritize structural and clinical aspects of designated women’s mental health care in the VHA. PMID:25642611

  17. Gynaecological Prolapse Surgery in Very Old Female Patients

    PubMed Central

    Mothes, A. R.; Lehmann, T.; Kwetkat, A.; Radosa, M. P.; Runnebaum, I. B.

    2016-01-01

    Background: The aim of this study is to compare very elderly female patients with a younger control group after prolapse surgery with regard to co-morbidity and complications. Method: In a case-control design, the consecutive data of patients after prolapse surgery at the age of over 80 years and those of a control group were analysed by means of the Clavien-Dindo (CD) classification of surgical complications, the Charlson Comorbidity Index and the Cumulative Illness Rating Scale Geriatrics (CIRS-G). Statistics: Studentʼs t, Fisherʼs exact and Mann-Whitney U tests. Results: The analysis comprised n = 57 vs. n = 60 operations. In the very elderly patients there was often a grade IV prolapse (p < 0.001), apical fixations were more frequent (p < 0.001), but the operating times were not different. In the very elderly patients 21 % CD II+III complications were observed, in the control group 6.6 % (p = 0.031). No CD IV and V complications occurred in either group, the duration of inpatient stay amounted to 5 (± 1) vs. 4.1 (± 0.8; p < 0.001) days, the very elderly patients needed an inpatient follow-up more frequently (p < 0.001). The co-morbidities of the very elderly patients differed from those of the control group in number (median 2.0 vs. 1.5; p < 0.001), in CIRS-G (4.1 ± 2.2 vs. 2.4 ± 1.7; p < 0.01) and in Charlson Index (1.6 ± 1.6 vs. 0.5 ± 0.7; p < 0.001). Conclusions: A prolapse in very elderly women can be safely managed by surgery. In no case did the complications require intensive care treatment nor were they life-threatening, but they did lead to a longer duration of hospital stay and more frequently to further treatment geriatric or inpatient internal medicine facilities. PMID:27582580

  18. Effect of Patients' Sex, Physicians' Attributes, and Patients' Complaint on Patients' Preference for Male vs Female Physicians.

    ERIC Educational Resources Information Center

    Ross, F. Susan Ackerman; Sochat N.

    In view of the dramatic increase in the number of women graduating from medical school in each of the past five years, this study explored patients' preferences for male versus female physicians. A questionnaire was designed to determine the patients' physician preferences in regard to each of the following areas: the sex of patient; the physician…

  19. Eight-Year Follow-Up of Neuropsychiatric Symptoms and Brain Structural Changes in Fabry Disease.

    PubMed

    Lelieveld, Irene M; Böttcher, Anna; Hennermann, Julia B; Beck, Michael; Fellgiebel, Andreas

    2015-01-01

    Brain structural alterations and neuropsychiatric symptoms have been described repeatedly in Fabry disease, yet cognitive deficits have been shown to be only mild. Here, we aimed to investigate neuropsychiatric symptoms and brain structure longitudinally. We expected no clinically relevant increase of neuropsychiatric symptoms in parallel to increased brain structural alterations. We assessed 14 Fabry patients (46.1 ± 10.8 years) who had participated in our investigation eight years ago. Patients engaged in neuropsychiatric testing, as well as structural magnetic resonance imaging and angiography to determine white matter lesions, hippocampal volume, and the diameter of the larger intracranial arteries. While Fabry patients did not differ on cognitive performance, they showed progressive and significant hippocampal volume loss over the 8-year observation period. White matter lesions were associated with older age and higher white matter lesion load at baseline, but did not reach statistical significance when comparing baseline to follow-up. Likewise, intracranial artery diameters did not increase significantly. None of the imaging parameters were associated with the neuropsychiatric parameters. Depression frequency reduced from 50% at baseline to 21% at follow-up, but it did not reach significance. This investigation demonstrates clinical stability in cognitive function, while pronounced hippocampal atrophy is apparent throughout the 8 years. Our middle-aged Fabry patients appeared to compensate successfully for progressive hippocampal volume loss. The hippocampal volume decline indicates brain regional neuronal involvement in Fabry disease.

  20. Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

    PubMed Central

    Namer, Barbara; Ørstavik, Kirstin; Schmidt, Roland; Mair, Norbert; Kleggetveit, Inge Petter; Zeidler, Maximillian; Martha, Theresa; Jorum, Ellen; Schmelz, Martin; Kalpachidou, Theodora; Kress, Michaela; Langeslag, Michiel

    2017-01-01

    The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons. PMID:28769867

  1. Comparison of acute non-haemolytic transfusion reactions in female and male patients receiving female or male blood components

    PubMed Central

    Imoto, S; Araki, N; Shimada, E; Saigo, K; Nishimura, K; Nose, Y; Bouike, Y; Hashimoto, M; Mito, H; Okazaki, H

    2007-01-01

    To study the relationship between antibodies detected in patients’ and/or donors’ sera and the clinical features of acute non-haemolytic transfusion reactions (ANHTRs), and to determine any gender-related difference. ANHTRs range from urticaria to transfusion-related acute lung injury (TRALI). Antibodies to human leukocyte antigen (HLA), granulocytes, platelets, and/or plasma proteins are implicated in some of the ANHTRs. A higher antibody positivity is expected for females than for males. A comparative study of ANHTRs for antibody positivity and their clinical features between females and males for both patients and donors is helpful for characterizing ANHTRs including TRALI more clearly, but such studies are few and outdated. Two hundred and twenty-three ANHTR cases reported by 45 hospitals between October 2000 and July 2005 were analysed. The patients and 196 donors of suspect blood products were screened for antibodies to HLA Class I, HLA Class II, granulocytes, and platelets. The patients were also screened for anti-plasma protein antibodies. The types and severity of ANHTR did not differ significantly between female and male patients. The frequency of the anti-HLA antibodies, but not that of the non-HLA antibodies, was significantly higher in females. Non-HLA antibodies were significantly associated with severe reactions in females. All the TRALI cases had predisposing risk factors for acute lung injury, and 60% of the cases showed anti-leucocyte antibodies. Although the anti-HLA antibodies were detected more frequently in females than males, no significant association of ANHTRs including TRALI with gender, not only for patients, but also for donors, could be shown in this study. PMID:18067650

  2. Anderson-Fabry disease: a case-finding study among male kidney transplant recipients in Austria.

    PubMed

    Kleinert, Julia; Kotanko, Peter; Spada, Marco; Pagliardini, Severo; Paschke, Eduard; Paul, Karl; Voigtländer, Till; Wallner, Manfred; Kramar, Reinhard; Stummvoll, Hans-Krister; Schwarz, Christoph; Horn, Sabine; Holzer, Herwig; Födinger, Manuela; Sunder-Plassmann, Gere

    2009-03-01

    The diagnosis of Anderson-Fabry disease is often delayed or even missed. As severe renal manifestations are a hallmark of alfa-galactosidase A (AGAL) deficiency, we tested the hypothesis that Anderson-Fabry disease is under-recognized among male kidney transplant recipients. This nation-wide study in Austria enrolled 1306 patients (ca 65% of all kidney transplanted males) from 30 kidney centers. AGAL activity was determined from filter paper dried blood spots by a fluorescence assay. A positive screening test was defined by an AGAL activity below 1.5 nmol/h/ml. In patients with a positive blood spot-screening test, AGAL activity was re-examined in peripheral blood leukocytes. Genetic testing for mutations in the GLA gene was performed by sequencing to confirm the diagnosis of Anderson-Fabry disease. Two previously not recognized cases with Anderson-Fabry disease were identified. Our study is the first showing that a diagnosis of Anderson-Fabry disease can be missed even in patients who undergo kidney transplantation. Case-finding strategies may be considered a useful tool for diagnosis of this rare disease that may be somewhat more prevalent among kidney transplant recipients compared with dialysis populations.

  3. Effect of juggling therapy on anxiety disorders in female patients

    PubMed Central

    Nakahara, Toshihiro; Nakahara, Kazuhiko; Uehara, Miho; Koyama, Ken-ichiro; Li, Kouha; Harada, Toshiro; Yasuhara, Daisuke; Taguchi, Hikaru; Kojima, Sinya; Sagiyama, Ken-ichiro; Inui, Akio

    2007-01-01

    Aims The aim of this study was to investigate the effect of juggling therapy for anxiety disorder patients. Design and Method Subjects were 17 female outpatients who met the DSM-IV diagnostic criteria for anxiety disorders. Subjects were treated with standard psychotherapy, medication and counseling for 6 months. For the last 3 months of treatment, subjects were randomized into either a non-juggling group (n = 9) or a juggling therapy group (juggling group: n = 8). The juggling group gradually acquired juggling skills by practicing juggling beanbags (otedama in Japan) with both hands. The therapeutic effect was evaluated using scores of psychological testing (STAI: State and Trate Anxiety Inventry, POMS: Profile of Mood Status) and of ADL (FAI: Franchay Activity Index) collected before treatment, 3 months after treatment (before juggling therapy), and at the end of both treatments. Results After 6 months, an analysis of variance revealed that scores on the state anxiety, trait anxiety subscales of STAI and tension-anxiety (T-A) score of POMS were significantly lower in the juggling group than in the non-juggling group (p < 0.01). Depression, anger-hostility scores of POMS were improved more than non-jugglers. In the juggling group, activity scores on the vigor subscale of POMS and FAI score were significantly higher than those in the non juggling group (p < 0.01). Other mood scores of POMS did not differ between the two groups. Conclusion These findings suggest that juggling therapy may be effective for the treatment of anxiety disorders. PMID:17470298

  4. α-Galactosidase A Genotype N215S Induces a Specific Cardiac Variant of Fabry Disease.

    PubMed

    Oder, Daniel; Liu, Dan; Hu, Kai; Üçeyler, Nurcan; Salinger, Tim; Müntze, Jonas; Lorenz, Kristina; Kandolf, Reinhard; Gröne, Hermann-Josef; Sommer, Claudia; Ertl, Georg; Wanner, Christoph; Nordbeck, Peter

    2017-10-01

    Hypertrophic cardiomyopathy is the most common type of cardiomyopathy, but many patients lack sarcomeric/myofilament mutations. We studied whether cardio-specific α-galactosidase A gene variants are misinterpreted as hypertrophic cardiomyopathy because of the lack of extracardiac organ involvement. All subjects who tested positive for the N215S genotype (n=26, 13 females, mean age 49±17 [range, 14-74] years) were characterized in this prospective monocentric longitudinal cohort study to determine genotype-specific clinical characteristics of the N215S (c.644A>G [p.Asn215Ser]) α-galactosidase A gene variant. All subjects were initially referred with suspicion of genetically determined hypertrophic cardiomyopathy. Cardiac hypertrophy (interventricular septum, 12±4 [7-23] mm; left ventricular posterior wall, 11±4 [7-21] mm; left ventricular mass, 86±41 [46-195] g/m(2)) was progressive, systolic function mainly preserved (cardiac index 2.8±0.6 [1.9-3.9] L/min per m(2)), and diastolic function mildly abnormal. Cardiac magnetic resonance imaging revealed replacement fibrosis in loco typico (18/26, 69%), particularly in subjects >50 years. Elderly subjects had advanced heart failure, and 6 (23%) were suggested for implantable cardioverter-defibrillator therapy. Leukocyte α-galactosidase A enzyme activity was mildly reduced in 19 subjects and lyso-globotriaosylceramide slightly elevated (median, 4.9; interquartile range, 1.3-9.1 ng/mL). Neurological and renal impairments (serum creatinine, 0.87±0.20; median, 0.80; interquartile range, 0.70-1.01 mg/dL; glomerular filtration rate, 102±23; median, 106; interquartile range, 84-113 mL/min) were discreet. Only 2 subjects developed clinically relevant proteinuria. α-Galactosidase A genotype N215S does not lead to the development of a classical Fabry phenotype but induces a specific cardiac variant of Fabry disease mimicking nonobstructive hypertrophic cardiomyopathy. The lack of prominent noncardiac impairment leads to

  5. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease

    PubMed Central

    Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  6. Enhancing the diagnosis of fabry disease in cardiology with a targeted information: a before–after control–impact study

    PubMed Central

    Savary, Anne-Louise; Morello, Remy; Brasse-Lagnel, Carole; Milliez, Paul; Bekri, Soumeya; Labombarda, Fabien

    2017-01-01

    Background Cardiac complications in Fabry disease are frequent and dominated by a high frequency of left ventricular hypertrophy; therefore, cardiologists may have an essential role in screening for this disease. Providing cardiologists with targeted information on Fabry disease would be valuable and could reduce both diagnostic and therapeutic delays. The aim of this study was to evaluate the efficiency of such strategy for Fabry screening. Methods We conducted a before–after control–impact study by comparing observations made before and after targeted information on Fabry disease among cardiologists. The information on Fabry disease consisted of (1) an educational booklet, (2) oral information and (3) screening kits. The programme was evaluated at the end of a 12-month study period. Results Forty-two cardiologists participated to this study. None of them had conducted screening test and new diagnostic for Fabry disease in the 3 years prior the information. After the information, screening with dried blood spots was performed in 55 patients (ranged 18–77 years, men: 39) with cardiac monitoring for supposed sarcomeric hypertrophic cardiomyopathy (n=41) or unexplained left ventricular hypertrophy (n=14) from January 2015 to January 2016. Two new cases of Fabry disease were diagnosed (3.4%) in two men (ages 58 and 51 years). The information was deemed relevant in both content and structure and was deemed useful for everyday practice. Conclusion Cardiologists valued the targeted information on Fabry disease. This information had a direct clinical impact by allowing the diagnosis of two new families with Fabry disease. PMID:28409012

  7. Myostatin signaling is up-regulated in female patients with advanced heart failure.

    PubMed

    Ishida, Junichi; Konishi, Masaaki; Saitoh, Masakazu; Anker, Markus; Anker, Stefan D; Springer, Jochen

    2017-07-01

    Myostatin, a negative regulator of skeletal muscle mass, is up-regulated in the myocardium of heart failure (HF) and increased myostatin is associated with weight loss in animal models with HF. Although there are disparities in pathophysiology and epidemiology between male and female patients with HF, it remains unclear whether there is gender difference in myostatin expression and whether it is associated with weight loss in HF patients. Heart tissue samples were collected from patients with advanced heart failure (n=31, female n=5) as well as healthy control donors (n=14, female n=6). Expression levels of myostatin and its related proteins in the heart were evaluated by western blotting analysis. Body mass index was significantly lower in female HF patients than in male counterparts (20.0±4.2 in female vs 25.2±3.8 in male, p=0.04). In female HF patients, both mature myostatin and pSmad2 were significantly up-regulated by 1.9 fold (p=0.05) and 2.5 fold (p<0.01) respectively compared to female donors, while expression of pSmad2 was increased by 2.8 times in male HF patients compared to male healthy subjects, but that of myostatin was not. There was no significant difference in protein expression related to myostatin signaling between male and female patients. In this study, myostatin and pSmad2 were significantly up-regulated in the failing heart of female patients, but not male patients, and female patients displayed lower body mass index. Enhanced myostatin signaling in female failing heart may causally contribute to pathogenesis of HF and cardiac cachexia. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Agalsidase alfa and kidney dysfunction in Fabry disease.

    PubMed

    West, Michael; Nicholls, Kathy; Mehta, Atul; Clarke, Joe T R; Steiner, Robert; Beck, Michael; Barshop, Bruce A; Rhead, William; Mensah, Robert; Ries, Markus; Schiffmann, Raphael

    2009-05-01

    In male patients with Fabry disease, an X-linked disorder of glycosphingolipid metabolism caused by deficient activity of the lysosomal enzyme alpha-galactosidase A, kidney dysfunction becomes apparent by the third decade of life and invariably progresses to ESRD without treatment. Here, we summarize the effects of agalsidase alfa on kidney function from three prospective, randomized, placebo-controlled trials and their open-label extension studies involving 108 adult male patients. The mean baseline GFR among 54 nonhyperfiltrating patients (measured GFR <135 ml/min per 1.73 m(2)) treated with placebo was 85.4 +/- 29.6 ml/min per 1.73 m(2); during 6 mo of placebo, the mean annualized rate of change in GFR was -7.0 +/- 32.9 ml/min per 1.73 m(2). Among 85 nonhyperfiltrating patients treated with agalsidase alfa, the annualized rate of change was -2.9 +/- 8.7 ml/min per 1.73 m(2). Treatment with agalsidase alfa did not affect proteinuria. Multivariate analysis revealed that GFR and proteinuria category (< 1 or > or = 1 g/d) at baseline significantly predicted the rate of decline of GFR during treatment. This summary represents the largest group of male patients who had Fabry disease and for whom the effects of enzyme replacement therapy on kidney function have been studied. These data suggest that agalsidase alfa may stabilize kidney function in these patients.

  9. Hyperspectral Thermal Fabry-Perot Modeling

    NASA Technical Reports Server (NTRS)

    Ryan, Robert; Blonski, Slawomir; Zanoni, Vicki; Stanley, Tom

    1999-01-01

    Fabry-Perot interferometer are simple elegant, tunable filters that can be used to make compact hyperspectral thermal imaging system. To foster the development of these sensors, software tools for the design and simulation of tunable Fabry-Perot infrared imagers have been developed. The tools are provided at three levels: basic, design, and system. Basic tools describe a nearly ideal Fabry-Perot filter with perfectly flat and parallel mirrors in collimated space. Design tools that take into account non-ideal behavior such as mirror and collimation defects calculate free spectral range, finesse, and spectral width of the interferometer. System tools help analyze an integration of the Fabry-Perot filter into a camera system. They include spectral convolution, first-order optical layout, and an estimation of signal-to-noise ratio. The complete set of tools allows for simulations of system operation and performance with various illumination sources. Spectral images generated in such simulations were used to examine applicability of Fabry-Perot system in remote sensing of atmospheric gases including detection of environmental pollutants and hazardous gases. Different operating conditions and system configurations are presented.

  10. Use of a Modified α-N-Acetylgalactosaminidase in the Development of Enzyme Replacement Therapy for Fabry Disease

    PubMed Central

    Tajima, Youichi; Kawashima, Ikuo; Tsukimura, Takahiro; Sugawara, Kanako; Kuroda, Mayuko; Suzuki, Toshihiro; Togawa, Tadayasu; Chiba, Yasunori; Jigami, Yoshifumi; Ohno, Kazuki; Fukushige, Tomoko; Kanekura, Takuro; Itoh, Kohji; Ohashi, Toya; Sakuraba, Hitoshi

    2009-01-01

    A modified α-N-acetylgalactosaminidase (NAGA) with α-galactosidase A (GLA)-like substrate specificity was designed on the basis of structural studies and was produced in Chinese hamster ovary cells. The enzyme acquired the ability to catalyze the degradation of 4-methylumbelliferyl-α-D-galactopyranoside. It retained the original NAGA's stability in plasma and N-glycans containing many mannose 6-phosphate (M6P) residues, which are advantageous for uptake by cells via M6P receptors. There was no immunological cross-reactivity between the modified NAGA and GLA, and the modified NAGA did not react to serum from a patient with Fabry disease recurrently treated with a recombinant GLA. The enzyme cleaved globotriaosylceramide (Gb3) accumulated in cultured fibroblasts from a patient with Fabry disease. Furthermore, like recombinant GLA proteins presently used for enzyme replacement therapy (ERT) for Fabry disease, the enzyme intravenously injected into Fabry model mice prevented Gb3 storage in the liver, kidneys, and heart and improved the pathological changes in these organs. Because this modified NAGA is hardly expected to cause an allergic reaction in Fabry disease patients, it is highly promising as a new and safe enzyme for ERT for Fabry disease. PMID:19853240

  11. Fibrosis: a key feature of Fabry disease with potential therapeutic implications

    PubMed Central

    2013-01-01

    Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that limits the therapeutic response to ERT. We provide an overview of Fabry disease, with a focus on the assessment of fibrosis, the clinical consequences of fibrosis, and recent advances in understanding the cellular and molecular mechanisms of fibrosis that may suggest novel therapeutic approaches to Fabry disease. PMID:23915644

  12. Fibrosis: a key feature of Fabry disease with potential therapeutic implications.

    PubMed

    Weidemann, Frank; Sanchez-Niño, Maria D; Politei, Juan; Oliveira, João-Paulo; Wanner, Christoph; Warnock, David G; Ortiz, Alberto

    2013-08-06

    Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that limits the therapeutic response to ERT. We provide an overview of Fabry disease, with a focus on the assessment of fibrosis, the clinical consequences of fibrosis, and recent advances in understanding the cellular and molecular mechanisms of fibrosis that may suggest novel therapeutic approaches to Fabry disease.

  13. Becker's Nevus Syndrome in a Pediatric Female Patient

    PubMed Central

    Hernandez-Quiceno, Sara; Ramírez-Jiménez, Juan Jose; Lopera-Cañaveral, Maria Victoria; Toro-Ramos, Martin; Usuga-Arcila, Yuri; Correa-Londoño, Luis; Martinez, Juan Camilo; Monroy, Jennifer; Alfaro, Juan Manuel

    2016-01-01

    Becker's nevus syndrome is part of the epidermal nevus syndromes and has been described with a phenotype that includes Becker's nevus, ipsilateral breast hypoplasia, and variable skeletal malformations. It is more frequent in males than in females (5 : 1) but is more relevant in females. The diagnosis is clinically based and the skin lesion must be present and no other numbered criteria have been established, but with more criteria being present the possibility of the diagnosis is higher. Regarding the treatment of breast hypoplasia, the use of antiandrogen medication has demonstrated adequate clinical response in a dose of 50 mg/day of spironolactone. PMID:27891278

  14. Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.

    PubMed

    Rombach, Saskia M; Aerts, Johannes M F G; Poorthuis, Ben J H M; Groener, Johanna E M; Donker-Koopman, Wilma; Hendriks, Erik; Mirzaian, Mina; Kuiper, Sijmen; Wijburg, Frits A; Hollak, Carla E M; Linthorst, Gabor E

    2012-01-01

    Enzyme replacement therapy (ERT) with alpha-Galactosidase A (aGal A) may cause antibody (AB) formation against aGal A in males with Fabry disease (FD). Anti agalsidase ABs negatively influence globotriaosylceramide (Gb3) reduction. We investigated the impact of agalsidase AB on Gb3 and lysoGb3 and clinical outcome in Fabry patients on ERT. Adult male and female patients on ERT for at least one year were included. Urinary Gb3 was measured by HPLC, plasma lysoGb3 by LC-ESI-MS/MS and AB with a neutralization assay. Of the 59 patients evaluable patients, 0/30 females and 17/29 males developed anti-agalsidase antibodies (AB+). Only 3/17 males had transient (low) titers (tolerized). All AB+ patients developed antibodies during the first year of treatment. Change of agalsidase preparation (or dose) did not induce antibody formation. AB+ males had significant less decline in plasma lysoGb3 compared to AB- males (p = 0.04). Urinary Gb3 levels decreased markedly in AB- but remained comparable to baseline in AB+ males (p<0.01). (Lyso)Gb3 reduction in plasma and urine on ERT was correlated with LVmass reduction in females and development white matter lesions and stroke. In male patients antibodies against aGal A remained present up to 10 years of ERT. The presence of these antibodies is associated with a less robust decrease in plasma lysoGb3 and a profound negative effect on urinary Gb3 reduction, which may reflect worse treatment outcome.

  15. Fabry disease, respiratory symptoms, and airway limitation – a systematic review

    PubMed Central

    Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke

    2015-01-01

    Background Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A, resulting in accumulation of glycosphingolipids in multiple organs, primarily heart, kidneys, skin, CNS, and lungs. Materials and method A systematic literature search was performed using the PubMed database, leading to a total number of 154 hits. Due to language restriction, this number was reduced to 135; 53 papers did not concern Fabry disease, 19 were either animal studies or gene therapy studies, and 36 papers did not have lung involvement in Fabry disease as a topic. The remaining 27 articles were relevant for this review. Results The current literature concerning lung manifestations describes various respiratory symptoms such as dyspnoea or shortness of breath, wheezing, and dry cough. These symptoms are often related to cardiac involvement in Fabry disease as respiratory examinations are seldom performed. Pulmonary function tests primarily show obstructive airway limitation, but a few articles also report of patients with restrictive limitation and a mixture of both. No significant association has been found between smoking and the development of symptoms or spirometry abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X-ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed by high-resolution CT has not been significantly correlated with lung spirometry. Conclusion Consistent findings have not been shown in the current literature. Pulmonary function tests and registration of symptoms showed various results; however, there is a trend towards obstructive airway limitation in patients with Fabry disease. Further studies are needed to evaluate pathogenesis, progression, and the effects of treatment. PMID:26557248

  16. Does geographical location influence the phenotype of Fabry disease in women in Europe?

    PubMed

    Barba-Romero, M-A; Deegan, P; Giugliani, R; Hughes, D

    2010-02-01

    This study examines the relationship between phenotype and geographical location of patients with Fabry disease in Europe. Data were taken from patients enrolled in the Fabry Outcome Survey (FOS), as of October 2007. A modified version of the Mainz Severity Score Index (FOS-MSSI) was used to classify patients according to the severity of disease. European patients were grouped depending on country of residence (northern or southern European countries). Results are presented from 762 patients enrolled in FOS in Europe (357 men and 405 women); 66% lived in northern and 34% in southern countries. Median age at onset of symptoms of Fabry disease was similar in both sexes. No differences in disease severity were seen among men, according to place of residence; however, women living in northern countries had higher severity scores (p < 0.001) than those in southern countries. In men and women, FOS-MSSI scores increased with age, irrespective of place of residence. The results suggest that expression of different phenotypic features in Fabry disease in women living in Europe may be influenced by extra-genetic or epigenetic factors. These factors might be related to dietary or environmental influences that differ according to the patient's country of residence.

  17. Cutaneous complications of Anderson-Fabry disease.

    PubMed

    Giuseppe, Pistone; Daniele, Rizzo; Rita, Bongiorno Maria

    2013-01-01

    Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by a defect in the α-galactosidase A gene, which leads to the deficiency of the hydrolytic enzyme α-galactosidase A. The consequent inability to catabolize glycosphingolipids causes progressive accumulation of globotriaosylceramide in the vascular endothelium throughout the body. Fatalities in the classical phenotype may usually occur as a consequence of cerebral, cardiac or renal disease. Dermatological manifestations are a relevant feature of Fabry disease and include angiokeratomas, telangiectasiae, lymphedema, anhidrosis or hypohidrosis and pseudo-acromegalic facial appearance. The actual causal treatment for Fabry disease is the enzyme replacement therapy. Dermatologists have a key role, since cutaneous manifestations may lead to the diagnosis. This may help an early therapeutic intervention, reducing both morbidity and mortality.

  18. Update on role of agalsidase alfa in management of Fabry disease

    PubMed Central

    Ramaswami, Uma

    2011-01-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder that affects both men and women. The manifestations of this heterogeneous disease are multisystemic and progressive. Prior to the development of enzyme replacement therapy, the management and treatment for Fabry disease was largely nonspecific and supportive. Because enzyme replacement therapy became commercially available in 2001, a variety of clinical benefits in Fabry patients have been consistently reported, including improved renal pathology and cardiac function, and reduced severity of neuropathic pain and improved pain-related quality of life. This update focuses on published data on the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa, and gives a brief overview on some of the outstanding management issues in the treatment of this complex disease. PMID:21552486

  19. Effectiveness of enzyme replacement therapy in Fabry disease: Long term experience in Argentina.

    PubMed

    Cabrera, Gustavo; Politei, Juan; Antongiovani, Norberto; Amartino, Hernán

    2017-06-01

    Evidence regarding long term effectiveness of enzyme replacement therapy (ERT) in Fabry disease (FD) is needed. The aim of this study was to analyze in a cohort of FD patients in Argentina, the long term effectiveness of ERT on renal, cardiac and cerebrovascular parameters. Patients with genetically proven FD were included from GADYTEF (Argentinean group for the treatment of FD) between 2001 and 2014. Renal, cardiac, and cerebral outcomes were prospectively studied in patients treated with ERT. Additionally, the occurrence of major cardiac complications, stroke, end-stage renal disease and death was analyzed during follow up. During the follow-up 8 major complications occurred in 5 patients (n = 2 deaths, n = 4 cases of end stage renal disease and n = 1 atrial fibrillation), 4 of them males and only 1 female who suffered an atrial fibrillation. Sudden death or stroke did not occur. Four (40%) of 10 males with baseline left ventricular hypertrophy (LVH) reduced left ventricular mass index (LVMI) from 163.1 ± 64.7 to 123.4 ± 49.8 g/m(2), 2 stabilized LVMI and 4 increased LVMI from157.9 ± 32.3 to 261.6 ± 48.6 g/m(2). Estimated glomerular filtration was stable in 30 patients (17 males and 13 females). We observed a few major complications during the follow up. Future studies are necessary to show the effectiveness of ERT in affected patients.

  20. Dynamic models of Fabry-Perot interferometers.

    PubMed

    Redding, David; Regehr, Martin; Sievers, Lisa

    2002-05-20

    Long-baseline, high-finesse Fabry-Perot interferometers can be used to make distance measurements that are precise enough to detect gravity waves. This level of sensitivity is achieved in part when the interferometer mirrors are isolated dynamically, with pendulum mounts and high-bandwidth cavity length control servos to reduce the effects of seismic noise. We present dynamical models of the cavity fields and signals of Fabry-Perot interferometers for use in the design and evaluation of length control systems for gravity-wave detectors. Models are described and compared with experimental data.

  1. Analysis of Fabry-Perot Velocimeter Records

    SciTech Connect

    Avara, G

    2001-08-03

    Program demonstration and user instructions are presented for FabryVB5. This computer program was created for use in analyzing Fabry-Perot interferometer records that detail the velocity time histories of fast moving surfaces. Graphical curves representing peak fringe positions and fiducial timing dots are extracted from a digitized film record or from a CCD digital image. An analysis is demonstrated on a sample velocimeter record along with some mathematical formula and routine operations. Routines used to analyze calibration records on streak camera distortions are illustrated in an appendix. This is a Microsoft Visual Basic{trademark} version for the PC.

  2. Strained layer Fabry-Perot device

    DOEpatents

    Brennan, Thomas M.; Fritz, Ian J.; Hammons, Burrell E.

    1994-01-01

    An asymmetric Fabry-Perot reflectance modulator (AFPM) consists of an active region between top and bottom mirrors, the bottom mirror being affixed to a substrate by a buffer layer. The active region comprises a strained-layer region having a bandgap and thickness chosen for resonance at the Fabry-Perot frequency. The mirrors are lattice matched to the active region, and the buffer layer is lattice matched to the mirror at the interface. The device operates at wavelengths of commercially available semiconductor lasers.

  3. Agalsidase alfa (Replagal) in the treatment of Anderson-Fabry disease.

    PubMed

    Pastores, Gregory M

    2007-09-01

    Anderson-Fabry disease (AFD) is an X-linked storage disorder caused by a deficiency of the lysosomal hydrolase a-galactosidase A (AGAL) and the resultant accumulation of its glycosphingolipid substrate (Gb3) in several tissue types. Major morbidity and reduced life expectancy among affected individuals are a consequence of renal, cardiac and cerebrovascular involvement. Symptomatic males and females with AFD have been described, although the onset of clinical manifestations may be delayed and more variable among the latter patient group, partly attributed to lyonization. Agalsidase alfa (Replagal()) is a recombinant formulation of human AGAL which has been demonstrated to modify the course of AFD in treated patients. Factors that may influence clinical outcomes include disease stage at the point of treatment initiation and antibody formation. There is incomplete understanding of AFD pathophysiology. Early diagnosis and timely intervention may be essential. The use of adjunctive therapies, directed at risk reduction (eg, aspirin for stroke prophylaxis), require careful scrutiny, but such agents are likely to be vital components of a comprehensive approach to patient care. Long-term studies may clarify the optimal dose and frequency of enzyme administration. Meanwhile, budding strategies such as chaperone-mediated enzyme enhancement may offer the potential for an alternative or multimodality approach to the management of AFD.

  4. The modified Latarjet procedure in female patients: clinical outcomes and complications.

    PubMed

    du Plessis, Jean-Pierre; Dachs, Robert P; Vrettos, Basil C; Maasdorp, David; Oliver, Joseph M A; Curtis, Saralee C; Roche, Stephen J L

    2017-09-21

    The aim of this study was to assess the short- and medium-term complications and clinical outcomes of female patients after a modified Latarjet procedure. A review of the literature was also conducted for outcomes of the modified Latarjet procedure in female patients and differences reported between male and female patients. We retrospectively reviewed the clinical notes of all female patients who had modified Latarjet procedures from 2001 with at least 1 year of follow-up. Patients were interviewed for an Oxford Shoulder Score, Western Ontario Shoulder Instability Index, Oxford Shoulder Instability Score, and subjective shoulder value. A literature review was performed of the electronic database PubMed; 343 papers were assessed for clinical outcomes based on gender. Twenty-nine patients were available for inclusion in the study. There were 13 complications in 11 patients (34%). The median postoperative Western Ontario Shoulder Instability Index score was 433; Oxford Shoulder Score, 42; and Oxford Shoulder Instability Score, 36. The median subjective shoulder value was 87%. Of these patients, 37.5% returned to sport. The reoperation rate was 13.8%. We found no literature reporting the outcomes of the modified Latarjet procedure in female patients. There are no published data comparing outcomes of the modified Latarjet procedure in male and female patients. Female patients had a lower postoperative return to sport and shoulder scores after the modified Latarjet procedure compared with literature reports. Whereas female gender should not be a contraindication to the Latarjet procedure, selection of patients in this group may need to be more stringent. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  5. GLA variation p.E66Q identified as the genetic etiology of Fabry disease using exome sequencing.

    PubMed

    Peng, Hao; Xu, Xiaojuan; Zhang, Lusi; Zhang, Xuehong; Peng, Hexiang; Zheng, Yu; Luo, Sanchuan; Guo, Hui; Xia, Kun; Li, Jiada; Yao, Hongliang; Hu, Zhengmao

    2016-01-10

    Fabry disease (FD) was an X-linked lysosomal storage disorder resulting from a deficiency in glycosphingolipid catabolism caused by mutations in the α-galactosidase A gene GLA. Variant FD patients did not present with classical symptoms during childhood and were undiagnosed or misdiagnosed with other kidney diseases, such as chronic glomerulonephritis (CGN). In this study, we utilized exome sequencing and Sanger sequencing identified the variation p.E66Q of GLA completely co-segregated with the disease phenotype in a Chinese family, which previously been diagnosed as possible CGN. Female patients exhibited preferential X-chromosome inactivation (XCI) of the normal p.E66 allele, as indicated by XCI analysis. By measuring α-Gal A activity, we found that male patients in the pedigree had just little enzymatic activity while female patients had residual enzymatic activity. These patients were diagnosed with renal variant FD in subsequent clinical review. Our results directly implicated the GLA mutation p.E66Q as the genetic etiology of the Chinese renal variant FD pedigree.

  6. Relationship Between Central Obesity and Spread of Spinal Anesthesia in Female Patients.

    PubMed

    Chang, Jee-Eun; Kim, Hyerim; Ryu, Jung-Hee; Lee, Jung-Man; Hwang, Jin-Young

    2017-05-01

    Central obesity may be related to the spread of spinal anesthesia in female patients. Fifty-seven female patients undergoing spinal anesthesia were allocated to either the central obesity or noncentral obesity group. After induction of spinal anesthesia, maximal sensory blockade (primary outcome), time for maximal sensory block, maximum motor block, time to maximum motor block, time to L2 regression, and time to Bromage scale 0 were evaluated. Multiple linear regression analyses showed that maximal sensory blockade was related to central obesity (P = .004). Central obesity is related to a more extensive spread of spinal anesthesia in female patients.

  7. Baseline Characteristics and Concerns of Female Cancer Patients/Survivors Seeking Treatment at a Female Sexual Medicine Program

    PubMed Central

    Carter, Jeanne; Stabile, Cara; Seidel, Barbara; Baser, Raymond E.; Gunn, Abigail R.; Chi, Stephanie; Steed, Rebecca F.; Goldfarb, Shari; Goldfrank, Deborah J.

    2016-01-01

    Purpose To characterize patients seeking treatment at a Female Sexual Medicine and Women’s Health Program and examine their sexual/vaginal health issues. Methods Data from clinical assessment forms were extracted from 509 women referred to the Female Sexual Medicine and Women’s Health Program during/after cancer treatment. The form consists of a Vaginal Assessment Scale [VAS], vaginal health items, patient-reported outcomes (PROs) (Sexual Activity Questionnaire [SAQ], Sexual Self-Schema Scale [SSS], Female Sexual Function Index [FSFI]), and exploratory items. Results Of 509 patients, 493 (97%) completed PROs; 253 (50%) received a pelvic examination. The majority had a history of breast (n=260, 51%), gynecologic (n=184, 36%), or colorectal/anal (n=35, 7%) cancer. Mean age was 51.2 years; 313 (62%) were married/partnered. Approximately two-thirds had elevated vaginal pH scores (5–6.5 [35%] or 6.5+ [33%]) and minimal (62%) or no (5%) vaginal moisture. Eighty-seven patients (44%) experienced pain during their exam (23% mild, 11% moderate, 1.5% severe, and 8.5% not indicated). Fifty-three percent engaged in sexual activity with a partner; only 43% felt confident about future sexual activity. Ninety-three percent were somewhat-to-very concerned/worried about sexual function/vaginal health. Approximately half had moderate/severe dryness (n=133, 51%) and dyspareunia (n=120, 46%). Mean SSS score was 60.7, indicating a slightly positive sexual self-view. However, 93.5% (n=429) had an FSFI score <26.55, suggesting sexual dysfunction. Conclusions At initial consult, women reported vaginal dryness, pain, and sexual dysfunction. For many women, pelvic exams showed elevated vaginal pH, lack of moisture, and discomfort with the exam itself. Future analyses will examine changes over time. PMID:25567673

  8. Hyperammonemia crisis following parturition in a female patient with ornithine transcarbamylase deficiency.

    PubMed

    Kido, Jun; Kawasaki, Tatsuya; Mitsubuchi, Hiroshi; Kamohara, Hidenobu; Ohba, Takashi; Matsumoto, Shirou; Endo, Fumio; Nakamura, Kimitoshi

    2017-02-28

    Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder, with an estimated prevalence of 1 per 80000 live births. Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders, such as genetic (private mutations and lyonization) and external factors; however, the outcomes of these conditions may differ. We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth. Hyperammonemia after parturition in a female patient with OTCD can be fatal, and this type of hyperammonemia persists for an extended period of time. Here, we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition. Once hyperammonemia crisis occurs after giving birth, it is difficult to improve the metabolic state. Therefore, it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.

  9. Hyperammonemia crisis following parturition in a female patient with ornithine transcarbamylase deficiency

    PubMed Central

    Kido, Jun; Kawasaki, Tatsuya; Mitsubuchi, Hiroshi; Kamohara, Hidenobu; Ohba, Takashi; Matsumoto, Shirou; Endo, Fumio; Nakamura, Kimitoshi

    2017-01-01

    Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder, with an estimated prevalence of 1 per 80000 live births. Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders, such as genetic (private mutations and lyonization) and external factors; however, the outcomes of these conditions may differ. We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth. Hyperammonemia after parturition in a female patient with OTCD can be fatal, and this type of hyperammonemia persists for an extended period of time. Here, we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition. Once hyperammonemia crisis occurs after giving birth, it is difficult to improve the metabolic state. Therefore, it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition. PMID:28293384

  10. 47,XYY karyotype and normal SRY in a patient with a female phenotype.

    PubMed

    Benasayag, S; Rittler, M; Nieto, F; Torres de Aguirre, N; Reyes, M; Copelli, S

    2001-06-01

    A rare case of a female patient with a 47,XYY karyotype is described. She had normal female external genitalia, bilateral testes, rudimentary Fallopian tubes and no uterus. Molecular analysis revealed a normal SRY encoding sequence. The possible events in the etiology of this sex reversal entity are discussed.

  11. Assessment of the female patient with urinary incontinence.

    PubMed

    Bates, Frankie

    2002-10-01

    Understanding the pelvic floor anatomy and all of its components is crucial when performing pelvic floor examination and assessing patients suffering from urinary incontinence. It is important for urology nurses to understand the pelvic floor, including the muscle, nerve, and fascia involved; external and internal examination of the vulva; and global assessment of the patient.

  12. 46,XX patients with congenital adrenal hyperplasia: initial assignment as male, reassigned female.

    PubMed

    Lee, Peter A; Witchel, Selma F

    2005-02-01

    Six 46,XX patients with congenital adrenal hyperplasia (CAH) presented with genital ambiguity, five so severe that initial gender assignment was male. Once diagnosis was realized, parents were involved in evaluation and chose sex re-assignment as female. To date, these girls and their parents all indicate satisfaction with their decision for a female sex of rearing. The girls have a female gender identity with behavior characteristics known for females with CAH. Thus, while outcome is satisfactory, it is realized that for most, expression of sexual orientation and adult life adjustments have not yet occurred.

  13. Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease.

    PubMed

    Hofmann, Lukas; Karl, Franziska; Sommer, Claudia; Üçeyler, Nurcan

    2017-01-01

    Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and naïve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors.

  14. Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease

    PubMed Central

    Karl, Franziska; Sommer, Claudia; Üçeyler, Nurcan

    2017-01-01

    Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and naïve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors. PMID:28662189

  15. Skewed X-inactivation in a tumor tissue from a female patient with leiomyomatosis

    SciTech Connect

    Kishino, T.; Jinno, Y.; Niikawa, N.

    1995-07-17

    Leiomyomatosis (multiple leiomyomas) is characterized by benign smooth muscle cell proliferations in the esophagus, tracheobronchial tree, and female genital tract. At least 3 genetically different hereditary leiomyomatoses have been identified. Among them, an X-linked leiomyomatosis is often associated with an Alport syndrome-like nephropathy. It has remained obscure whether the leiomyomata occur monoclonally or polyclonally. The clonality of various malignancies has been examined by analysis of X-inactivation patterns in female patients heterozygous for polymorphic alleles of X-linked genes. We examined the clonality of a leiomyoma in a female patient by a polymerase chain reaction (PCR)-based X-inactivation assay. 6 refs., 1 fig.

  16. The effect of office based flexible and rigid cystoscopy on pain experience in female patients

    PubMed Central

    Vriesema, Jessica L.; Stomps, Saskia P.; van Balen, Olav L.W.B.; Cornel, Erik B.

    2017-01-01

    Purpose Rigid and flexible cystoscopies are both routinely used in female patients. Literature is conflicting whether flexible cystoscopy is less painful compared to rigid cystoscopy. The aim of this study was therefore to investigate whether using flexible cystoscopy leads to less discomfort and pain compared to rigid cystoscopy in female patients who underwent first time cystoscopy. Materials and Methods One hundred eighty-nine female patients, who never had undergone cystoscopy, were randomized into 2 groups: 92 patients underwent rigid cystoscopy and 97 patients flexible cystoscopy. Directly after the cystoscopy procedure all patients were asked to fill out their pain experience on a 100-mm visual analogue pain scale (VAS). Results Median VAS score was significantly lower for women undergoing flexible cystoscopy (0 [0–20]) compared to rigid cystoscopy (15 [0–38], p<0.001). In addition, age was inversely associated with VAS score, indicating that younger females experienced more pain (R=−0.30, p=0.001). The use of flexible cystoscopy was associated with a decrease in VAS score and remained significant after adjustment for age, sex of urologist, performing urologist and indication (standardized β=−0.17, p=0.048). Conclusions The use of flexible cystoscopy resulted in a significantly lower pain experience compared to rigid cystoscopy. Based on patient's pain experience during cystoscopy, this study implicates to use flexible cystoscopy in female patients who undergo first time cystoscopy. PMID:28097268

  17. The effect of office based flexible and rigid cystoscopy on pain experience in female patients.

    PubMed

    Casteleijn, Niek F; Vriesema, Jessica L; Stomps, Saskia P; van Balen, Olav L W B; Cornel, Erik B

    2017-01-01

    Rigid and flexible cystoscopies are both routinely used in female patients. Literature is conflicting whether flexible cystoscopy is less painful compared to rigid cystoscopy. The aim of this study was therefore to investigate whether using flexible cystoscopy leads to less discomfort and pain compared to rigid cystoscopy in female patients who underwent first time cystoscopy. One hundred eighty-nine female patients, who never had undergone cystoscopy, were randomized into 2 groups: 92 patients underwent rigid cystoscopy and 97 patients flexible cystoscopy. Directly after the cystoscopy procedure all patients were asked to fill out their pain experience on a 100-mm visual analogue pain scale (VAS). Median VAS score was significantly lower for women undergoing flexible cystoscopy (0 [0-20]) compared to rigid cystoscopy (15 [0-38], p<0.001). In addition, age was inversely associated with VAS score, indicating that younger females experienced more pain (R=-0.30, p=0.001). The use of flexible cystoscopy was associated with a decrease in VAS score and remained significant after adjustment for age, sex of urologist, performing urologist and indication (standardized β=-0.17, p=0.048). The use of flexible cystoscopy resulted in a significantly lower pain experience compared to rigid cystoscopy. Based on patient's pain experience during cystoscopy, this study implicates to use flexible cystoscopy in female patients who undergo first time cystoscopy.

  18. Optimism, pessimism and self-efficacy in female cancer patients.

    PubMed

    Thieme, Maik; Einenkel, Jens; Zenger, Markus; Hinz, Andreas

    2017-09-01

    The aim of this examination was to study whether psychological resource variables (optimism and self-efficacy) decrease when cancer is present and to test the predictive power of these variables for anxiety, depression and quality of life (QoL). The patient sample was comprised of 354 German women suffering from breast cancer or gynecological cancer. Participants filled in the resource assessment tools Life Orientation Test-Revised and the General Self-Efficacy Scale as well as the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-4 and the QoL instrument EORTC QLQ-C30 at two time points: (t1) during patients' hospital stay and (t2) 3 months later. The mean scores for optimism (total score: M = 16.2) and self-efficacy (M = 29.8) were even somewhat higher than the corresponding means of the general population. Optimism and self-efficacy were positively correlated with QoL (r between 0.15 and 0.17, P < 0.01) and negatively associated with anxiety and depression (r between -0.17 and -0.36, P < 0.01). However, only optimism was predictive of the t2 anxiety, depression and QoL scores when statistically taking into account the baseline levels of the outcome variables. Having cancer does not generally reduce optimism and self-efficacy on the level of patients' mean scores. Cancer patients with a high level of habitual optimism will adapt to their disease better than pessimistic patients, even if the baseline levels of the outcome variables have been accounted for.

  19. The relationship between body esteem, exercise motivations, depression, and social support among female free clinic patients.

    PubMed

    Kamimura, Akiko; Christensen, Nancy; Al-Obaydi, Sarah; Solis, Silvia Patricia; Ashby, Jeanie; Greenwood, Jessica L J; Reel, Justine J

    2014-01-01

    Obesity is a significant public health problem in women's health. This study examined relationship between body esteem, exercise motivations, depression, and social support among female free clinic patients. Low-income women who are at risk for obesity and other health concerns would benefit from health education efforts. We compared 299 female and 164 male free clinic patients 18 years or older using assessments for body esteem, motivation to exercise, depression, and social support. Although female participants reported lower levels of body esteem and higher levels of depression compared with male participants (p < .01), female participants were more motivated to exercise for weight-related reasons than male participants (p < .05). U.S.-born female participants reported lower exercise motivations compared with non-U.S.-born female participants (p < .01). Social support might be an important factor to increase exercise motivation among female free clinic patients (p < .05); depression lowers levels of body esteem (p < .01). The results of this study suggest that female free clinic patients should receive gender-specific interventions to promote positive body image and physical activity. It is important for health educators to engage a myriad of physical activity motives to increase the likelihood that clients will experience enjoyment and sustained adoption of exercise into their lifestyle. Future practice and research should warrant the implementation of body image and physical activity programs and the potential impact of using exercise to reducing depression among female patients at free clinics. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  20. Sexual Concerns of Male Spouses of Female Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Litz, Brett T.; And Others

    1990-01-01

    Presents case study which highlights attendant cognitive changes that occur in Alzheimer's patient, presenting caregiver with challenges to couple's sexual functioning. Describes man who reported erectile dysfunction directly stemming from stressful changes that had occurred in his relationship to his wife who had Alzheimer's disease. General…

  1. Sexual Concerns of Male Spouses of Female Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Litz, Brett T.; And Others

    1990-01-01

    Presents case study which highlights attendant cognitive changes that occur in Alzheimer's patient, presenting caregiver with challenges to couple's sexual functioning. Describes man who reported erectile dysfunction directly stemming from stressful changes that had occurred in his relationship to his wife who had Alzheimer's disease. General…

  2. Clinical characteristics of male and female Korean patients with systemic lupus erythematosus: a comparative study.

    PubMed

    Hwang, Jiwon; Lee, Jaejoon; Ahn, Joong Kyoung; Park, Eun-Jung; Cha, Hoon-Suk; Koh, Eun-Mi

    2015-03-01

    To compare the clinical characteristics and outcomes of systemic lupus erythematosus between male and female Korean patients. A retrospective analysis was performed at a single tertiary hospital from August 1994 to May 2010. Male patients were matched with two to three female patients based on age and disease duration. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SLICC/ACR DI). Fifty-three male patients were compared with 150 female patients. Renal disorders were found more frequently in male patients at disease onset (p < 0.001); the adjusted odds ratio (OR) demonstrated a significant sex preponderance for renal manifestations (OR, 3.26; 95% confidence interval [CI], 1.62 to 6.57). Diffuse proliferative lupus nephritis and end-stage renal disease requiring dialysis during the disease course were more prevalent in male patients (p = 0.025 and p < 0.001, respectively). The risk for requiring long-term dialysis was significantly higher in male than in female patients (OR, 4.02; 95% CI, 1.07 to 15.06), as was the mean SLICC/ACR DI (1.55 ± 1.35 vs. 1.02 ± 1.57, respectively; p = 0.028). Our data demonstrate that Korean patients with lupus have characteristics similar to those of cohorts reported previously. Male patients had significantly higher incidences of renal manifestations and organ damage.

  3. Survival Outcomes and Predictive Factors for Female Urethral Cancer: Long-term Experience with Korean Patients.

    PubMed

    Kang, Minyong; Jeong, Chang Wook; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

    2015-08-01

    The aim of this study was to evaluate female urethral cancer (UCa) patients treated and followed-up during a time period spanning more than 20 yr at single institution in Korea. We reviewed medical records of 21 consecutive patients diagnosed with female UCa at our institution between 1991 and 2012. After exclusion of two patients due to undefined histology, we examined clinicopathological variables, as well as survival outcomes of 19 patients with female UCa. A Cox proportional hazards ratio model was used to identify significant predictors of prognosis according to variables. The median age at diagnosis was 59 yr, and the median follow-up duration was 87.0 months. The most common initial symptoms were voiding symptoms and blood spotting. The median tumor size was 3.4 cm, and 55% of patients had lesions involving the entire urethra. The most common histologic type was adenocarcinoma, and the second most common type was urothelial carcinoma. Fourteen patients underwent surgery, and 7 of these patients received adjuvant radiation or systemic chemotherapy. Eleven patients experienced tumor recurrence after primary therapy. Patients with high stage disease, advanced T stage (≥T3), and positive lymph nodes had worse survival outcomes compared to their counterparts. Particularly, lymph node positivity and advanced T stage were significant predictive factors for all survival outcomes. Tumor location was the only significant predictor for recurrence-free survival. Although our study included a small number of patients, it conveys valuable information about this rare female urologic malignancy in a Korean population.

  4. Female Sexual Dysfunction in Presymptomatic Mutation Carriers and Patients with Huntington's Disease.

    PubMed

    Kolenc, Matej; Kobal, Jan; Podnar, Simon

    2017-01-01

    Although in Huntington's disease (HD) movement, cognition, and personality are most significantly affected, autonomic dysfunction should not be neglected. In women with HD sexual dysfunction has not been adequately studied yet. To report sexual dysfunction in a systematically studied cohort of female HD patients and compare it with controls of a similar age. In female HD patients and presymptomatic HD mutation carriers, we compared the Female Sexual Function Index (FSFI) questionnaire, neurologic assessment using the Unified Huntington's Disease Rating Scale (UHDRS) and the Total Functional Capacity (TFC). Of 44 female HD patients and 9 presymptomatic HD mutation carriers, 30 HD patients and 8 HD mutation carriers responded our invitation to complete FFSI questionnaire. Finally, 23 HD women with a partner were compared to 47 controls with a partner. HD patients had more problems with sexual arousal, lubrication, orgasm and sexual satisfaction. By contrast, we found no difference in sexual desire and pain. Sexual dysfunction progressed in parallel with the decline in the TFC; severe sexual dysfunction occurred with TFC <7/13. Our study demonstrated a significant impact of HD on female sexual function that progressed with patients' functional decline and impaired patients' quality of life. Sexual dysfunction may be caused by progression of the disease itself, side effects of medication, and comorbidities like depression or dementia.

  5. A fe/male transsexual patient in psychoanalysis.

    PubMed

    Quinodoz, D

    1998-02-01

    The author describes the analysis of a transsexual who had undergone a vaginoplasty as a young man and had since been living as a woman. The complexity of the psychic reality is epitomised by the analyst's difficulty in deciding whether to use masculine or feminine grammatical forms to refer to this patient. The author tells how she assumed the fantasy role of parents expecting a baby whose sex they did not yet know. She discusses at length her hesitation about accepting a transsexual patient into analysis and reports how she overcame her misgivings after analysing her own countertransference and consulting the literature. Noting that this borderline analysand resorted to both psychotic and neurotic mechanisms, the analyst decided to rely on the capacity for symbolisation and mental representation evinced in the latter. On the psychotic level, the delusional neo-reality of the appearance of a woman sought to replace the unbearable reality of being a man, whereas the neurotic part was aware that s/he could never really be a woman. The author observes that in this analysand sexualisation served to conceal a fundamental narcissistic fault. She also describes how she worked with her own madness to help the patient emerge from a situation of paradoxical fusion with the mother in madness.

  6. Bulbocavernosus Reflex Test for Diagnosis of Pudendal Nerve Injury in Female Patients with Diabetic Neurogenic Bladder

    PubMed Central

    Niu, Xiaoting; Wang, Xun; Huang, Huanjie; Ni, Peiqi; Lin, Yuanshao; Shao, Bei

    2016-01-01

    The study was designed to investigate the clinical application and significance of the bulbocavernosus reflex (BCR) test for diagnosing diabetic neurogenic bladder (DNB) in female subjects. In this study, 68 female patients with DNB and 40 female normal controls were subjected to a nerve conduction study (NCS) of all four limbs and the BCR test. The data were analyzed and compared, and the corresponding diagnostic sensitivities were discussed. Mean BCR latency for female DNB patients was significantly prolonged, compared to that of the control group, suggesting pudendal nerve injuries in female DNB patients. Moreover, DNB patients were categorized according to the diabetes course. Compared to that of Group A (diabetes course < 5 y), the mean BCR latency was significantly prolonged in Group B (diabetes course between 5 and 10 y) and then further prolonged in Group C (diabetes course > 10 y), which were all longer than the control group. Furthermore, compared with that of the controls, the mean BCR latency was prolonged in DNB patients with or without NCS abnormalities in limbs. Nevertheless, no significant difference was observed in BCR latency between DNB patients with and without NCS abnormalities. Significantly increasing trends were also observed in the NCS and BCR abnormality rates along with increased diabetes course. Most importantly, compared with the NCS of limbs, the BCR test was more sensitive in diagnosing DNB in the female subjects. Overall, our findings suggest that the BCR test would help to assess the pudendal nerve injury in female DNB patients, which might be a potential diagnostic tool in the clinic. PMID:28053822

  7. Case study on the pathophysiology of Fabry Disease: Abnormalities of cellular membranes can be reversed by substrate reduction in vitro.

    PubMed

    Brogden, Graham; Shammas, Hadeel; Maalouf, Katia; Naim, Samara L; Wetzel, Gabi; Amiri, Mahdi; von Köckritz-Blickwede, Maren; Das, Anibh M; Naim, Hassan Y

    2017-03-28

    It is still not entirely clear how a-galactosidase (GAA) deficiency translates into clinical symptoms of Fabry disease (FD). The current communication investigates the effects of the mutation N215S in FD on the trafficking and processing of lysosomal GAA and their potential association with alterations in the membrane lipid composition. Abnormalities in lipid rafts were observed in fibroblasts isolated from a male patient with Fabry disease bearing the mutation N215S. Interestingly, lipid raft analysis revealed that the distribution of cholesterol and flotillin-2 are distinctly altered in the Fabry fibroblasts when compared to that of wild type cells. Furthermore, increased levels of glycolipid Gb3 (globotriaosylceramide 3) and sphingomyelin were observed in non-raft membrane fractions of Fabry cells. Substrate reduction with N-butyldeoxynojirimycin in vitro was capable of reversing these abnormalities in this patient. These data lead to the hypothesis that alterations of lipid rafts may contribute to the pathophysiology of Morbus Fabry. Furthermore, it may be suggested that substrate reduction therapy with N-butyldeoxynojirimycin might be a promising approach for the treatment of GAA-deficiency at least for selected patients.

  8. Female gender lost protective effect against disease progression in elderly patients with chronic hepatitis B

    PubMed Central

    You, Hong; Kong, Yuanyuan; Hou, Jinlin; Wei, Lai; Zhang, Yuexin; Niu, Junqi; Han, Tao; Ou, Xiaojuan; Dou, Xiaoguang; Shang, Jia; Tang, Hong; Xie, Qing; Ding, Huiguo; Ren, Hong; Xu, Xiaoyuan; Xie, Wen; Liu, Xiaoqing; Xu, Youqing; Li, Yujie; Li, Jie; Chow, Shein-Chung; Zhuang, Hui; Jia, Jidong

    2016-01-01

    Female gender and younger age are protective factors against disease progression in chronic hepatitis B (CHB). However, it is not clear whether the disease progression still remains slow in elderly females. This study investigated the interaction of female gender and older age on the development of cirrhosis in patients recorded in China Registry of Hepatitis B. A total of 17,809 CHB patients were enrolled in this multi-center cross-sectional study. The prevalence of cirrhosis in female CHB patients increased faster than that in male CHB patients over 50 years old. Multivariate analysis showed that the increase of adjusted ORs for developing cirrhosis in females started to accelerate after 50 years old: 11.19 (95% CI: 5.93–21.11) in women versus 14.75 (95% CI: 8.35–26.07) in men at ages of 50–59 years, 21.67 (95% CI: 11.05–42.47) versus 24.4 (95% CI: 13.00–45.80) at ages 60–69 years, and 18.78 (95% CI: 6.61–53.36) versus 12.09 (95% CI: 4.35–33.61) in those over 70 years. In conclusion, the protective effect of female gender against cirrhosis gradually lost with increasing age, therefore disease progression should be monitored more closely in elderly women with CHB. PMID:27892487

  9. Comparison of Hospital Mortality and Readmission Rates for Medicare Patients Treated by Male vs Female Physicians

    PubMed Central

    Tsugawa, Yusuke; Jena, Anupam B.; Figueroa, Jose F.; Orav, E. John; Blumenthal, Daniel M.; Jha, Ashish K.

    2017-01-01

    IMPORTANCE Studies have found differences in practice patterns between male and female physicians, with female physicians more likely to adhere to clinical guidelines and evidence-based practice. However, whether patient outcomes differ between male and female physicians is largely unknown. OBJECTIVE To determine whether mortality and readmission rates differ between patients treated by male or female physicians. DESIGN, SETTING, AND PARTICIPANTS We analyzed a 20% random sample of Medicare fee-for-service beneficiaries 65 years or older hospitalized with a medical condition and treated by general internists from January 1, 2011, to December 31, 2014. We examined the association between physician sex and 30-day mortality and readmission rates, adjusted for patient and physician characteristics and hospital fixed effects (effectively comparing female and male physicians within the same hospital). As a sensitivity analysis, we examined only physicians focusing on hospital care (hospitalists), among whom patients are plausibly quasi-randomized to physicians based on the physician’s specific work schedules. We also investigated whether differences in patient outcomes varied by specific condition or by underlying severity of illness. MAIN OUTCOMES AND MEASURES Patients’ 30-day mortality and readmission rates. RESULTS A total of 1 583 028 hospitalizations were used for analyses of 30-day mortality (mean [SD] patient age, 80.2 [8.5] years; 621 412 men and 961 616 women) and 1 540 797 were used for analyses of readmission (mean [SD] patient age, 80.1 [8.5] years; 602 115 men and 938 682 women). Patients treated by female physicians had lower 30-day mortality (adjusted mortality, 11.07% vs 11.49%; adjusted risk difference, −0.43%; 95% CI, −0.57% to −0.28%; P < .001; number needed to treat to prevent 1 death, 233) and lower 30-day readmissions (adjusted readmissions, 15.02% vs 15.57%; adjusted risk difference, −0.55%; 95% CI, −0.71% to −0.39%; P < .001; number

  10. Fourier Transform Fabry-Perot Interferometer

    NASA Technical Reports Server (NTRS)

    Snell, Hilary E.; Hays, Paul B.

    1992-01-01

    We are developing a compact, rugged, high-resolution remote sensing instrument with wide spectral scanning capabilities. This relatively new type of instrument, which we have chosen to call the Fourier-Transform Fabry-Perot Interferometer (FT-FPI), is accomplished by mechanically scanning the etalon plates of a Fabry-Perot interferometer (FPI) through a large optical distance while examining the concomitant signal with a Fourier-transform analysis technique similar to that employed by the Michelson interferometer. The FT-FPI will be used initially as a ground-based instrument to study near-infrared atmospheric absorption lines of trace gases using the techniques of solar absorption spectroscopy. Future plans include modifications to allow for measurements of trace gases in the stratosphere using spectral lines at terahertz frequencies.

  11. Fourier Transform Fabry-Perot Interferometer

    NASA Technical Reports Server (NTRS)

    Snell, Hilary E.; Hays, Paul B.

    1992-01-01

    We are developing a compact, rugged, high-resolution remote sensing instrument with wide spectral scanning capabilities. This relatively new type of instrument, which we have chosen to call the Fourier-Transform Fabry-Perot Interferometer (FT-FPI), is accomplished by mechanically scanning the etalon plates of a Fabry-Perot interferometer (FPI) through a large optical distance while examining the concomitant signal with a Fourier-transform analysis technique similar to that employed by the Michelson interferometer. The FT-FPI will be used initially as a ground-based instrument to study near-infrared atmospheric absorption lines of trace gases using the techniques of solar absorption spectroscopy. Future plans include modifications to allow for measurements of trace gases in the stratosphere using spectral lines at terahertz frequencies.

  12. What Do Clinicians Expect?: Comparing Envisioned and Reported Violence for Male and Female Patients

    ERIC Educational Resources Information Center

    Skeem, Jennifer L.; Mulvey, Edward P.; Odgers, Candice; Schubert, Carol; Stowman, Stephanie; Gardner, William; Lidz, Charles

    2005-01-01

    Mental health professionals' (MHPs') accuracy in assessing the risk of violence in female patients is particularly limited. Based on assessments made by 205 MHPs of 605 patients in an emergency room, this study explored potential causes of MHPs' poorer accuracy in assessing women's potential for violence. The dimensions that underlie MHPs'…

  13. Female Genital Dialogues: Female Genital Self-Image, Sexual Dysfunction, and Quality of Life in Patients With Vitiligo With and Without Genital Affection.

    PubMed

    Sarhan, Deena; Mohammed, Ghada F A; Gomaa, Amal H A; Eyada, Moustafa M K

    2016-01-01

    Vitiligo has a major effect on sexual health because of the disfiguring skin lesions affecting self-image and self-esteem. However, this topic has not explored. This article aimed to assess the effect of vitiligo on genital self-image, sexual function, and quality of life in female patients. This cross-sectional study included 50 sexually active women with vitiligo and 25 women without vitiligo. All participants subjected to full history taking and examination. Extent of vitiligo was assessed with the Vitiligo Area Scoring Index score, sexual function with the Female Sexual Function Index, genital self-image with Female Genital Self-Image Score and quality of life with the Dermatology Life Quality Index questionnaires. The main outcome measures were correlation between Vitiligo Area Scoring Index, Female Genital Self-Image Score, Female Sexual Function Index, and Dermatology Life Quality Index domains was determined using t test and Pearson correlation. This study revealed a negative correlation between the Vitiligo Area Scoring Index score and sexual satisfaction. Vitiligo Area Scoring Index and Dermatology Life Quality Index score was significantly correlated with Arabic Version of the Female Genital Self-Image Score alone and with Arabic Version of the Female Sexual Functioning Index alone and with both the Arabic Version of the Female Genital Self-Image Score and the Arabic Version of the Female Sexual Functioning Index (p <.05). Sexual and psychological assessment of patients with vitiligo is imperative to improve outcomes and increase patients' compliance with treatment.

  14. Fertility preservation in female cancer patients: An overview

    PubMed Central

    Mahajan, Nalini

    2015-01-01

    Fertility preservation is becoming increasingly important to improve the quality of life in cancer survivors. Despite guidelines suggesting that discussion of fertility preservation should be done prior to starting cancer therapies, there is a lack of implementation in this area. A number of techniques are available for fertility preservation, and they can be used individually or together in the same patient to maximize efficiency. Oocyte and embryo cryopreservation are now established techniques but have their limitations. Ovarian tissue cryopreservation though considered experimental at present, has a wider clinical application and the advantage of keeping the fertility window open for a longer time. Both chemotherapy and radiotherapy have a major impact on reproductive potential and fertility preservation procedures should be carried out prior to these treatments. The need for fertility preservation has to be weighed against morbidity and mortality associated with cancer. There is thus a need for a multidisciplinary collaboration between oncologists and reproductive specialists to improve awareness and availability. PMID:25838742

  15. Dietary Intake In Adult Female Coeliac Disease Patients In Slovenia

    PubMed Central

    Mičetić-Turk, Dušanka

    2016-01-01

    Abstract Objectives The aim of the study was to assess dietary intake of coeliac disease (CD) patients and to determine if they are meeting the dietary reference values for a balanced diet. Subjects/Methods 40 women with CD, aged from 23 to 76 participated in our study. Total daily intake was assessed by a three-day food diary. Resting metabolic rate (RMR) was calculated using Harris-Benedict equation. Considering physical activity level (PAL) 1.4, the recommended total energy expenditure (TEE) value was determined. The data was evaluated with professional evaluation software Prodi and statistically analysed. Results 40 participants returned the food diary. The average energy intake was significantly too low to ensure the meeting of all-day energy needs (p<0.05). The meals contained a recommended proportion of protein, but a statistically significantly higher proportion of fat (p<0.05), lower proportion of carbohydrates and a significantly lower intake of dietary fibre (p<0.05). Regarding macro-, micro- elements and vitamins, there was a significant lack in the intake of calcium and iodine, folic acid, vitamin D and vitamin A (p<0.05), meanwhile iron intake was at the lower limit of the recommended intake, whereas zinc, potassium and vitamin K intake were significantly higher according to the recommended values, but were comparable with the intake of the general population in the Central European area. Conclusion Even in subjects with adequate or low daily energy intake, their meals contained too much fat, too few carbohydrates and dietary fibre as well as inorganic substances. The patients with CD should get regular nutritional monitoring and education on the quality and balance of a gluten-free diet. PMID:27284377

  16. Establishing 3-nitrotyrosine as a biomarker for the vasculopathy of Fabry disease

    PubMed Central

    Shu, Liming; Vivekanandan-Giri, Anuradha; Pennathur, Subramaniam; Smid, Bouwien E; Aerts, Johannes M FG; Hollak, Carla E M; Shayman, James A

    2014-01-01

    The endothelial dysfunction of Fabry disease results from α-galactosidase A deficiency leading to the accumulation of globotriaosylceramide. Vasculopathy in the α-galactosidase A null mouse is manifested as oxidant-induced thrombosis, accelerated atherogenesis, and impaired arterial reactivity. To better understand the pathogenesis of Fabry disease in humans, we generated a human cell model by using RNA interference. Hybrid endothelial cells were transiently transfected with small interfering RNA (siRNA) specifically directed against α-galactosidase A. Knockdown of α-galactosidase A was confirmed using immunoblotting and globotriaosylceramide accumulation. Endothelial nitric oxide synthase (eNOS) activity was correspondingly decreased by >60%. Levels of 3-nitrotyrosine (3NT), a specific marker for reactive nitrogen species and quantified using mass spectrometry, increased by 40- to 120-fold without corresponding changes in other oxidized amino acids, consistent with eNOS-derived reactive nitrogen species as the source of the reactive oxygen species. eNOS uncoupling was confirmed by the observed increase in free plasma and protein-bound aortic 3NT levels in the α-galactosidase A knockout mice. Finally, 3NT levels, assayed in biobanked plasma samples from patients with classical Fabry disease, were over sixfold elevated compared with age- and gender-matched controls. Thus, 3NT may serve as a biomarker for the vascular involvement in Fabry disease. PMID:24402087

  17. Fabry-Perot cavity hydrostatic pressure sensors

    NASA Astrophysics Data System (ADS)

    Carvalho, L.; Roriz, P.; Simões, J.; Santos, J. L.; Frazão, O.

    2014-05-01

    Interferometric fiber optic based sensors, namely those based on the Fabry-Perot (F-P) configuration seem very attractive for biomechanical and biomedical applications. The present study is focused on the proof of concept of two developed FP based sensors, for high and low pressure measurements of fluids. For low pressure sensor, it was used a polymeric diaphragm in a microstrutured fiber. It was obtained a good agreement between wavelength shift and the pressure, for the two tested sensors.

  18. Extrinsic Fabry-Perot ultrasonic detector

    NASA Astrophysics Data System (ADS)

    Kidwell, J. J.; Berthold, John W., III

    1996-10-01

    We characterized the performance of a commercial fiber optic extrinsic Fabry-Perot interferometer for use as an ultrasonic sensor, and compared the performance with a standard lead zirconate titanate (PZT) detector. The interferometer was unstabilized. The results showed that the fiber sensor was about 12 times less sensitive than the PZT detector. Ultrasonic frequency response near 100 kHz was demonstrated. We describe the design of the fiber sensor, the details of the tests performed, and potential applications.

  19. Fabry disease: characterisation of the plasma proteome pre- and post-enzyme replacement therapy.

    PubMed

    Heo, Sun Hee; Kang, Eungu; Kim, Yoon-Myung; Go, Heounjeong; Kim, Kyung Yong; Jung, Jae Yong; Kang, Minji; Kim, Gu-Hwan; Kim, Jae-Min; Choi, In-Hee; Choi, Jin-Ho; Jung, Sung-Chul; Desnick, Robert J; Yoo, Han-Wook; Lee, Beom Hee

    2017-08-23

    Fabry disease is characterised by the progressive accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in vascular endothelial cells. Enzyme replacement therapy (ERT) clears this accumulation. We analysed plasma proteome profiles before and after ERT to characterise its molecular pathology. Two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight tandem mass spectrometry (MALDI-TOF MS) and tandem mass spectrometry (MS/MS) were done using plasma samples before and after ERT in eight patients with classical Fabry disease RESULTS: After short-term ERT (4-12 months), the levels of 15 plasma proteins involved in inflammation, oxidative and ischaemic injury, or complement activation were reduced significantly. Among them, β-actin (ACTB), inactivated complement C3b (iC3b), and C4B were elevated significantly in pre-ERT Fabry disease plasma compared with control plasma. After longer-term ERT (46-96 months), iC3b levels gradually decreased, whereas the levels of other proteins varied. The gradual reduction of iC3b was comparable to that of Gb3 levels. In addition, iC3b increased significantly in pre-ERT Fabry disease mouse plasma, and C3 deposits were notable in renal tissues of pre-enzyme replacement therapy patients. These results indicated that C3-mediated complement activation might be altered in Fabry disease and ERT might promote its stabilisation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. An Archetype Semi-Ring Fabry-Perot (SRFP) Resonator

    NASA Technical Reports Server (NTRS)

    Taghavi-Larigani, Shervin; VanZyl, Jakob

    2009-01-01

    We introduce and demonstrate the generation of a novel resonator, termed Semi-Ring Fabry-Perot (SRFP), that exhibits unique features, such as, its use of one plane mirror, allowing the SRFP to be easily fabricated as a symmetrical device. In addition to its unique features, it exhibits advantages of ring and Fabry-Perot resonators: 1) compared to a ring resonator that only allows a transmitted intensity, the Semi-Ring Fabry-Perot (SRFP) supports standing waves, allowing both a reflected and transmitted intensity; 2) the reflected light spectrum of the SRFP resonator is much narrower than similar Fabry-Perot, implying higher finesse.

  1. A simple method for quantification of plasma globotriaosylsphingosine: Utility for Fabry disease.

    PubMed

    Talbot, Andrew; Nicholls, Kathy; Fletcher, Janice M; Fuller, Maria

    2017-09-01

    Fabry disease (FD) results from impaired globotriaosylceramide (Gb3) catabolism, due to a deficiency of the lysosomal hydrolase, α-galactosidase A (α-GalA). As a direct consequence, the deacetylated derivative, globotriaosylsphingosine (lyso-Gb3), is produced and contemporary evidence exemplifies its use as a biomarker. Here we developed a simple method to enable quantification of lyso-Gb3 in just 0.01mL of plasma and explored its concentration in a cohort of 73 Australian FD patients, as well as in individuals with other sphingolipidoses. In 2000 patients without FD, but with related metabolic conditions, lyso-Gb3 returned concentrations of <5pmol/mL. In the FD cohort, 53/60 patients with classical mutations returned lyso-Gb3 concentrations≥5pmol/mL whereas only 4/13 patients with "late-onset" mutations had lyso-Gb3≥5pmol/mL. Five females with normal α-GalA activity and genetically confirmed FD returned lyso-Gb3≥5pmol/mL. The prevalence of clinically significant disease including cardiomyopathy, nephropathy and cerebrovascular disease was congruent with higher lyso-Gb3 concentrations. Repeat testing was available for 51 patients-26 undergoing enzyme replacement therapy-and concentrations of lyso-Gb3 remained unaltered throughout 6-18 months independent of sex, mutation or treatment status. Our data suggest that the optimum use of lyso-Gb3 resides in laboratory confirmation of classical FD and for monitoring at least the initial response to therapeutic intervention. There is no evidence that lyso-Gb3 can inform on clinical events. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Quality of life, depression, and sexual dysfunction in spouses of female patients with fibromyalgia.

    PubMed

    Tutoglu, Ahmet; Boyaci, Ahmet; Koca, Irfan; Celen, Esra; Korkmaz, Nurdan

    2014-08-01

    The aim of this study was to investigate the effects of the quality of life and psychological condition of female patients with fibromyalgia and their spouses on sexual function. A total of 32 female patients diagnosed with fibromyalgia and their spouses were analyzed. Thirty married couples were included in the study as the control group. The demographic data of the fibromyalgia patients were recorded, a visual analog scale was used to evaluate the level of pain, and the Fibromyalgia Impact Questionnaire was used to evaluate the impact of the symptoms on the quality of life of the patients. The quality of life of both the patients and the control group were evaluated using the Short Form 36 (SF-36), and psychological variables were evaluated using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory. Sexual function was assessed using the Female Sexual Function Index for female participants and the International Index of Erectile Function (IIEF) for male participants. The IIEF erectile dysfunction scores were significantly lower in the spouses of female patients with fibromyalgia than in the control group (p < 0.05), and the BDI scores were significantly higher in the spouses of the female patients with fibromyalgia (p < 0.05). Among the SF-36 scores, the emotional and physical roles were significantly lower in the spouses of the female patients with fibromyalgia (p = 0.003 and p = 0.004, respectively). In all spouses of FMS patients and controls, there was a significantly negative correlation between erectile function, the BDI score, and to be married with FMS patient and positive correlations between erectile function and emotional role, social function, mental health, SF-36 pain score, and general health (p < 0.05 for all). In a linear regression model, BDI, to be married with FMS patient and general health were found to affect erectile function (beta regression coefficient = -0.572, SE = 0.082, p = 0.001; beta regression coefficient = -0.332, SE = 1

  3. Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium.

    PubMed

    Moon, James C C; Sachdev, Bhavesh; Elkington, Andrew G; McKenna, William J; Mehta, Atul; Pennell, Dudley J; Leed, Philip J; Elliott, Perry M

    2003-12-01

    Anderson-Fabry Disease (AFD), an X-linked disorder of sphingolipid metabolism, is a cause of idiopathic left ventricular hypertrophy but the mechanism of hypertrophy is poorly understood. Gadolinium enhanced cardiovascular magnetic resonance can detect focal myocardial fibrosis. We hypothesised that hyperenhancement would be present in AFD. Eighteen males (mean 43+/-14 years) and eight female heterozygotes (mean 48+/-12 years) with AFD underwent cine and late gadolinium cardiovascular magnetic resonance. Nine male (50%) had myocardial hyperenhancement ranging from 3.4% to 20.6% (mean 7.7+/-5.7%) of total myocardium; in males, percentage hyperenhancement related to LV mass index (r=0.78, P=0.0002) but not to ejection fraction or left ventricular volumes. Lesser hyperenhancement was also found in four (50%) heterozygous females (mean 4.6%). In 12 (92%) patients with abnormal gadolinium uptake, hyperenhancement occurred in the basal infero-lateral wall where, unlike myocardial infarction, it was not sub-endocardial. In two male patients with severe LVH (left ventricular hypertrophy) and systolic impairment there was additional hyperenhancement in other myocardial segments. These observations suggests that myocardial fibrosis occurs in AFD and may contribute to the hypertrophy and the natural history of the disease.

  4. Identification of intellectual disability genes in female patients with a skewed X inactivation pattern

    PubMed Central

    Fieremans, Nathalie; Van Esch, Hilde; Holvoet, Maureen; Van Goethem, Gert; Devriendt, Koen; Rosello, Monica; Mayo, Sonia; Martinez, Francisco; Jhangiani, Shalini; Muzny, Donna M.; Gibbs, Richard A.; Lupski, James R.; Vermeesch, Joris R.; Marynen, Peter; Froyen, Guy

    2016-01-01

    Intellectual disability (ID) is a heterogeneous disorder with an unknown molecular etiology in many cases. Previously, X-linked ID (XLID) studies focused on males due to the hemizygous state of their X chromosome. Carrier females are generally unaffected due to the presence of a second normal allele, or inactivation of the mutant X chromosome in most of their cells (skewing). However, in female ID patients, we hypothesized that the presence of skewing of X-inactivation would be an indicator for an X chromosomal ID cause. We analysed the X-inactivation patterns of 288 females with ID, and found that 22 (7.6%) had extreme skewing (>90%), which is significantly higher than observed in the general population (3.6%; p=0.029). Whole exome sequencing of 19 females with extreme skewing revealed causal variants in 6 females in the XLID genes DDX3X, NHS, WDR45, MECP2 and SMC1A. Interestingly, variants in genes escaping X-inactivation presumably cause both XLID and skewing of X-inactivation in 3 of these patients. Moreover, variants likely accounting for skewing only, were detected in MED12, HDAC8 and TAF9B. All tested candidate causative variants were de novo events. Hence, extreme skewing is a good indicator for the presence of X-linked variants in female patients. PMID:27159028

  5. Identification of Intellectual Disability Genes in Female Patients with a Skewed X-Inactivation Pattern.

    PubMed

    Fieremans, Nathalie; Van Esch, Hilde; Holvoet, Maureen; Van Goethem, Gert; Devriendt, Koenraad; Rosello, Monica; Mayo, Sonia; Martinez, Francisco; Jhangiani, Shalini; Muzny, Donna M; Gibbs, Richard A; Lupski, James R; Vermeesch, Joris R; Marynen, Peter; Froyen, Guy

    2016-08-01

    Intellectual disability (ID) is a heterogeneous disorder with an unknown molecular etiology in many cases. Previously, X-linked ID (XLID) studies focused on males because of the hemizygous state of their X chromosome. Carrier females are generally unaffected because of the presence of a second normal allele, or inactivation of the mutant X chromosome in most of their cells (skewing). However, in female ID patients, we hypothesized that the presence of skewing of X-inactivation would be an indicator for an X chromosomal ID cause. We analyzed the X-inactivation patterns of 288 females with ID, and found that 22 (7.6%) had extreme skewing (>90%), which is significantly higher than observed in the general population (3.6%; P = 0.029). Whole-exome sequencing of 19 females with extreme skewing revealed causal variants in six females in the XLID genes DDX3X, NHS, WDR45, MECP2, and SMC1A. Interestingly, variants in genes escaping X-inactivation presumably cause both XLID and skewing of X-inactivation in three of these patients. Moreover, variants likely accounting for skewing only were detected in MED12, HDAC8, and TAF9B. All tested candidate causative variants were de novo events. Hence, extreme skewing is a good indicator for the presence of X-linked variants in female patients. © 2016 WILEY PERIODICALS, INC.

  6. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

    PubMed Central

    Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

    2006-01-01

    Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder

  7. Catastrophic antiphospholipid antibody syndrome presenting as acute vascular occlusion in a young female patient.

    PubMed

    Alonso, Joaquín Valle; Del Pozo, Francisco Javier Fonseca; Álvarez, Manuel Vaquero; Pedraza, Jorge; Aguayo, Miguel Angel; Sanchez, Almudena

    2016-10-10

    Acquired thrombotic and thromboembolic disorders may be presented initially with symptoms and signs of acute ischaemia or organ dysfunction that will lead many of these patients to seek care in the emergency department. We report a case of a 19-year-old female patient who developed catastrophic antiphospholipid syndrome (CAPS syndrome or Asherson syndrome) 6 weeks post stillbirth with an initial presentation of acute vascular occlusion. The patient was immediately operated and anticoagulated with significant improvement.

  8. Severe intimate partner violence and alcohol use among female trauma patients.

    PubMed

    Weinsheimer, R L; Schermer, C R; Malcoe, L H; Balduf, L M; Bloomfield, L A

    2005-01-01

    The lifetime prevalence of intimate partner violence (IPV) among women in the United States is reported to be between 18 and 50%. One-third of female homicide victims are killed by an intimate partner and alcohol is often involved. Despite these figures, 77% of women have never been screened for IPV. Substance abuse in male partners is known to place women at risk. We examined the role of female alcohol use on rates of severe IPV. Our hypotheses were: (1) the prevalence of IPV among women seen in trauma centers is greater than that found in national surveys; (2) alcohol problems among abused women and their partners are greater than those among non-abused women; (3) females and their partners alcohol problems are each independently associated with IPV; and (4) female trauma center patients support domestic violence screening. An in-person survey was administered to 95 consecutive adult female trauma patients admitted to a Level I Trauma Center. The survey included questions about past-year and lifetime severe IPV, female and male partner alcohol use, and willingness to participate in IPV screening and referral. The multivariate associations of female and partner alcohol use with past-year severe IPV were assessed with logistic regression. Nearly one-half (46.3%) of women reported a lifetime history of severe IPV, with 26% experiencing severe IPV in the past year. Past-year IPV was identified in 59.1% of women screening positive for drinking problems, but in only 12.7% of those screening negative for drinking problems (p = 0.001). Similarly, past-year IPV prevalence was 55.2% when the partner was a problem drinker versus 8.3% when he was not (p = 0.001). Multivariate analysis showed that female problem drinking (odds ratio [OR] = 5.8) and partner problem drinking (OR=8.9) were independent predictors of past-year severe IPV. The majority of women (90.5%) felt that it was appropriate for health care professionals to screen for IPV; 90% of women with a history of IPV

  9. Study of functional brain homogeneity in female patients with major depressive disorder.

    PubMed

    Zhang, X; Tang, Y; Zhu, Y; Li, Y; Tong, S

    2016-08-01

    Women are at a twofold higher risk of developing major depressive disorder (MDD) than that of men. However, the investigation of female MDD patients functional brain activity is rare and the detailed mechanism remains unclear. The present work is to explore the altered spontaneous neural activity measured with regional homogeneity (ReHo) in female MDD patients using resting-state functional magnetic resonance imaging (fMRI) technique. Twelve MDD females and twelve matched healthy participants were included in the study. The ReHo analysis method was used to detect regional homogeneity features across the whole brain. Increased ReHo value was found in the left anterior cingulate gyrus (ACC_L) and right fusiform gyrus, and decreased ReHo value in the right putamen, left middle frontal gyrus and left middle occipital gyrus was shown in female MDD patients compared to healthy controls. Also, a significant positive correlation between patients ReHo value and HAMA score (r = 0.59, p = 0.045) was found in the ACC_L. The study of spontaneous neuronal activity alteration using ReHo analysis improves our understanding about the mechanism of female depression.

  10. Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.

    PubMed

    Kreuter, Alexander; Kryvosheyeva, Yulia; Terras, Sarah; Moritz, Rose; Möllenhoff, Katrin; Altmeyer, Peter; Scola, Nina; Gambichler, Thilo

    2013-03-27

    Lichen sclerosus is a relatively common chronic inflammatory skin disease that predominantly affects the anogenital area. Accumulating evidence indicates that lichen sclerosus in women may be associated with other autoimmune disease, whereas this association seems to lack in male patients. We retrospectively evaluated the prevalence of autoimmune diseases and serological parameters indicative for autoimmunity in male and female patients with lichen sclerosus. Of the 532 patients (396 women, 136 men; 500 adults, 32 children; mean age: 49 years; range 1-89 years; female:male ratio 3:1), 452 (85%) had genital and 80 (15%) had extragenital disease. In women, lichen sclerosus was significantly more often associated with at least one autoimmune disease as compared to men (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.9-9.6; p<0.0001). Moreover, female patients with lichen sclerosus had sinificantly more often associated autoimmune thyroid diseases (OR 4.7, 95% CI 1.8-11.9; p<0.0002), antithyroid-antibodies (OR 2.7, 95% CI 1.1-6.5; p=0.023), and elevated autoantibodies (OR 4.1, 95% CI 1.9-9.3; p<0.0001) as compared to male patients. This observation is suggestive for a different pathogenetic background in male and female patients.

  11. Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics.

    PubMed

    Favalli, Valentina; Disabella, Eliana; Molinaro, Mariadelfina; Tagliani, Marilena; Scarabotto, Anna; Serio, Alessandra; Grasso, Maurizia; Narula, Nupoor; Giorgianni, Carmela; Caspani, Clelia; Concardi, Monica; Agozzino, Manuela; Giordano, Calogero; Smirnova, Alexandra; Kodama, Takahide; Giuliani, Lorenzo; Antoniazzi, Elena; Borroni, Riccardo G; Vassallo, Camilla; Mangione, Filippo; Scelsi, Laura; Ghio, Stefano; Pellegrini, Carlo; Zedde, Marialuisa; Fancellu, Laura; Sechi, GianPietro; Ganau, Antonello; Piga, Stefania; Colucci, Annarita; Concolino, Daniela; Di Mascio, Maria Teresa; Toni, Danilo; Diomedi, Marina; Rapezzi, Claudio; Biagini, Elena; Marini, Massimiliano; Rasura, Maurizia; Melis, Maurizio; Nucera, Antonia; Guidetti, Donata; Mancuso, Michelangelo; Scoditti, Umberto; Cassini, Pamela; Narula, Jagat; Tavazzi, Luigi; Arbustini, Eloisa

    2016-09-06

    Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients. In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations. Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively. Screening probands with clinically

  12. Differences in the treatment of male and female patients with end-stage renal disease.

    PubMed Central

    Florakas, C; Wilson, R; Toffelmire, E; Godwin, M; Morton, R

    1994-01-01

    OBJECTIVE: To determine whether there is a difference in the allocation of types of dialysis to male and female patients with end-stage renal disease (ESRD). DESIGN: Descriptive study. SETTING: Canada. PATIENTS: All patients registered with the Canadian Organ Replacement Register (CORR) whose treatment began between 1981 and 1991. Data were obtained for 19,732 patients, of whom 18,010 had sufficiently complete data and were being treated with either peritoneal dialysis or hemodialysis 3 months after the diagnosis of ESRD. OUTCOME MEASURES: Proportions of patients receiving peritoneal dialysis and hemodialysis according to sex. RESULTS: Significantly more male (58.1%) than female (50.8%) patients were receiving hemodialysis 3 months after diagnosis (p < 0.00001). Multivariate analysis to control for the possible confounding effects of age, province of treatment, diagnosis, concurrent illness and year of diagnosis did not explain the difference. CONCLUSIONS: In Canada from 1981 to 1991 male patients were more likely than female patients to receive hemodialysis for the treatment of ESRD. Additional research is needed to explain this finding. PMID:7954176

  13. Separate patient serum sodium medians from males and females provide independent information on analytical bias.

    PubMed

    Hansen, Steen Ingemann; Petersen, Per Hyltoft; Lund, Flemming; Fraser, Callum G; Sölétormos, György

    2017-04-27

    During monitoring of monthly medians of results from patients undertaken to assess analytical stability in routine laboratory performance, the medians for serum sodium for male and female patients were found to be significantly related. Daily, weekly and monthly patient medians of serum sodium for both male and female patients were calculated from results obtained on samples from the population >18 years on three analysers in the hospital laboratory. The half-range of medians was applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated. The medians of both genders demonstrated dispersions over time, but they were closely connected in like patterns, which were confirmed by the half-range of the ratios of medians for males and females that varied from 0.36% for daily, 0.14% for weekly and 0.036% for monthly ratios over all instruments. The tight relationship between the gender medians for serum sodium is only possible when raw laboratory data are used for calculation. The two patient medians can be used to confirm both and are useful as independent estimates of analytical bias during constant calibration periods. In contrast to the gender combined median, the estimate of analytical bias can be confirmed further by calculation of the ratios of medians for males and females.

  14. Proinflammatory proteins in female and male patients with primary antiphospholipid syndrome: preliminary data.

    PubMed

    Bećarević, Mirjana; Ignjatović, Svetlana

    2016-10-01

    The latest classification criteria for the diagnosis of the antiphospholipid syndrome (APS, an autoimmune disease characterized by thromboses, miscarriages and presence of antiphospholipid antibodies (Abs)) emphasized that thrombotic manifestations of APS should be without any signs of an inflammatory process. However, atherosclerosis (a chronic inflammatory response to the accumulation of lipoproteins in the walls of arteries) and APS are characterized by some similar features. We evaluated whether proinflammatory proteins were associated with the features of the primary APS (PAPS). PAPS patients without obstetric complications and with impaired lipid profile were included in the study. Antiphospholipid antibodies, TNF-alpha, and apo(a) were determined by ELISA. Complement components and hsCRP were measured by immunonephelometry. Decreased C3c was observed in female patients with increased titers of IgG anti-β2gpI (χ(2) = 3.939, P = 0.047) and in male patients with increased IgM anticardiolipin Abs (χ(2) = 4.286, P = 0.038). Pulmonary emboli were associated with interleukin (IL)-6 in male (χ(2) = 6.519, P = 0.011) and in female (χ(2) = 10.405, P = 0.001) patients. Cerebrovascular insults were associated with LDL-cholesterol (P = 0.05, 95 % CI: 1.003 - 12.739) in female and with apo(a) (P = 0.016, 95 % CI: 0.000-0.003) in male patients. Older female patients had increased LDL-cholesterol levels and frequency of myocardial infarctions. Proinflammatory proteins were associated with features of primary APS. No real gender differences in regard to proinflammatory protein levels were observed. Premenopausal state of female PAPS patients confers lower cardiovascular risk.

  15. Plasma mutant α-galactosidase A protein and globotriaosylsphingosine level in Fabry disease.

    PubMed

    Tsukimura, Takahiro; Nakano, Sachie; Togawa, Tadayasu; Tanaka, Toshie; Saito, Seiji; Ohno, Kazuki; Shibasaki, Futoshi; Sakuraba, Hitoshi

    2014-01-01

    Fabry disease is an X-linked genetic disorder characterized by deficient activity of α-galactosidase A (GLA) and accumulation of glycolipids, and various GLA gene mutations lead to a wide range of clinical phenotypes from the classic form to the later-onset one. To investigate the biochemical heterogeneity and elucidate the basis of the disease using available clinical samples, we measured GLA activity, GLA protein and accumulated globotriaosylsphingosine (Lyso-Gb3), a biomarker of this disease, in plasma samples from Fabry patients. The analysis revealed that both the enzyme activity and the protein level were apparently decreased, and the enzyme activity was well correlated with the protein level in many Fabry patients. In these cases, a defect of biosynthesis or excessive degradation of mutant GLAs should be involved in the pathogenesis, and the residual protein level would determine the accumulation of Lyso-Gb3 and the severity of the disease. However, there are some exceptional cases, i.e., ones harboring p.C142Y, p.R112H and p.M296I, who exhibit a considerable amount of GLA protein. Especially, a subset of Fabry patients with p.R112H or p.M296I has been attracted interest because the patients exhibit almost normal plasma Lyso-Gb3 concentration. Structural analysis revealed that C142Y causes a structural change at the entrance of the active site. It will lead to a complete enzyme activity deficiency, resulting in a high level of plasma Lyso-Gb3 and the classic Fabry disease. On the other hand, it is thought that R112H causes a relatively large structural change on the molecular surface, and M296I a small one in a restricted region from the core to the surface, both the structural changes being far from the active site. These changes will cause not only partial degradation but also degeneration of the mutant GLA proteins, and the degenerated enzymes exhibiting small and residual activity remain and probably facilitate degradation of Lyso-Gb3 in plasma, leading

  16. Novel α-Galactosidase A Mutation (K391E) in a Young Woman With Severe Cardiac and Renal Manifestations of Fabry Disease.

    PubMed

    Wakakuri, Hiroaki; Nakamura, Shunichi; Utsumi, Kouichi; Shimizu, Wataru; Yasutake, Masahiro

    2016-09-28

    Fabry disease, an X-linked lysosomal storage disorder due to α-galactosidase A deficiency, is associated with dysfunction of various cell types and results in a systemic vasculopathy. We describe a 29-year-old woman with Fabry disease presenting with severe cardiac and renal manifestations. Gene analysis demonstrated a novel mutation (K391E) in the GLA gene. Enzyme replacement therapy (ERT) was started with agalsidase-β after confirming the diagnosis of Fabry disease, resulting in normalization of LV systolic function and improvement of renal function. As early therapy is crucial for preventing life-threatening sequelae, clinicians should consider Fabry disease in young patients presenting with cardiac and renal disease without any likely causes.

  17. Angiotensinogen promoter and angiotensinogen II receptor type 1 gene polymorphisms and incidence of ischemic stroke and neurologic phenotype in Fabry disease.

    PubMed

    Altarescu, Gheona; Haim, Shimon; Elstein, Deborah

    2013-11-01

    Stroke and/or white matter lesions (WMLs) are significant in Fabry disease. Polymorphisms of angiotensinogen (AGT), AGT Promoter and angiotensinogen II receptor type 1 (AGTR1) are correlated with WMLs. We compared AGT. AGT Promoter and AGTR1 genotypes to stroke incidence, Fabry-specific [Mainz Severity Score Index (MSSI)] severity score, and neurologic sub-score (n-MSSI). Sixty-three Fabry patients and 49 matched controls plus historic controls were genotyped. Institutional Review Board approval was received. Results. C and/or CC alleles of AGT Promoter and AGTR1 were significantly correlated with stroke and n-MSSI. Findings are suggestive of role of AGT Promoter and AGTR1 genotypes in Fabry phenotypes.

  18. Gender identity and gender role orientation in female assigned patients with disorders of sex development.

    PubMed

    Mattila, Aino K; Fagerholm, Riitta; Santtila, Pekka; Miettinen, Päivi J; Taskinen, Seppo

    2012-11-01

    Gender identity and gender role orientation were assessed in 24 female assigned patients with disorders of sex development. A total of 16 patients were prenatally exposed to androgens, of whom 15 had congenital adrenal hyperplasia and 1 was virilized due to maternal tumor. Eight patients had 46,XY karyotype, of whom 5 had partial and 3 had complete androgen insensitivity syndrome. Gender identity was measured by the 27-item Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults with 167 female medical students as controls, and gender role was assessed by the femininity and masculinity subscales of the 30-item Bem Sex Role Inventory with 104 female and 64 male medical students as controls. No patient reached the cutoff for gender identity disorder on the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. However, patients with 46,XY karyotype demonstrated a somewhat more conflicted gender identity, although the overall differences were relatively small. As to gender role orientation, patients with complete androgen insensitivity syndrome had high scores on the femininity and masculinity scales of the Bem Sex Role Inventory, which made them the most androgynous group. Our findings, although clinically not clear cut, suggest that patients with disorders of sex development are a heterogeneous group regarding gender identity and gender role outcomes, and that this issue should be discussed with the family when treatment plans are made. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  19. Atrial Fibrillation is Associated With Morphine Treatment in Female Breast Cancer Patients

    PubMed Central

    Lee, Cynthia Wei-Sheng; Muo, Chih-Hsin; Liang, Ji-An; Lin, Ming-Chia; Kao, Chia-Hung

    2016-01-01

    Abstract We investigated the relationship between morphine treatment and the risk of atrial fibrillation (AF) in female patients with breast cancer. We identified a malignancy cohort of 73,917 female breast cancer patients without an AF history before the date of breast cancer diagnosis between 2000 and 2010 by using the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. This malignancy cohort was divided into morphine and comparison cohorts comprising 18,671 and 55,246 patients, respectively, and the incidences of newly diagnosed AF were calculated. We used the Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of AF. The effect of morphine was assessed through multivariable Cox proportional hazard regression controlling for age, the Charlson comorbidity index (CCI) score, and the use of bisphosphonates and paclitaxel. Compared with nonmorphine users, patients who received morphine exhibited a 4.37-fold (95% CI = 3.56–5.36) increase in the risk of developing AF. The risk of AF increased as the CCI score increased, but decreased in patients with tamoxifen treatment. This risk is especially significant in current morphine users of all ages and with low CCI score. AF risk increased as the duration of morphine use lengthened (P for trend <0.0001). The incidence of AF in female breast cancer patients in Taiwan is associated with morphine, but prevented by tamoxifen treatment. PMID:26986153

  20. A comparative analysis of nutritional parameters as predictors of outcome in male and female ESRD patients.

    PubMed

    Stenvinkel, Peter; Barany, Peter; Chung, Sung Hee; Lindholm, Bengt; Heimbürger, Olof

    2002-07-01

    Many patients with end-stage renal disease (ESRD) are malnourished and cross-sectional studies show that markers of malnutrition may predict death. Serum albumin (S-albumin), the commonest nutritional marker, has been criticized because it is so closely related to the effects of inflammation and other non-nutritional factors. Consequently, we need other nutritional markers that can predict outcome. However, males and females differ as regards body composition and it is not known how this may influence the predictive power of different nutritional markers. In 206 ESRD patients (126 males) aged 52+/-1 years, we evaluated the relationship between survival and five estimates of nutritional status (S-albumin, subjective global assessment (SGA), lean body mass (LBM), body fat mass (FM) assessed by dual-energy X-ray absorptiometry, and handgrip strength (HGS)) close to start of renal replacement therapy (RRT). The patients were also classified as regards the presence of cardiovascular disease (CVD), diabetes mellitus (DM), and inflammation (CRP> or = 10 mg/l). Mortality was monitored over mean follow-up period of 37+/-2 months. In the whole patient group, the presence of CVD, DM, inflammation, and malnutrition (SGA >1) close to start of RRT all predicted poor outcome. However, whereas inflammation strongly predicted (P<0.0001) poor outcome in males, no such effect was observed in females. Also, differences were found between males and females regarding the predictive value of the five different nutritional estimates. Whereas HGS, SGA, and S-albumin independently predicted poor outcome in males, only SGA predicted outcome (independently of age, CVD, and DM) in females. Mild to moderate malnutrition, as assessed by SGA, was present in 39% of the patients and predicted outcome independently of age and co-morbidity in both males and females. However, the predictive power of various other nutritional markers differed markedly between male and female patients. Whereas a low HGS

  1. Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance.

    PubMed

    Urban, Renata R; Teng, Nelson N H; Kapp, Daniel S

    2011-05-01

    We report a case of uterine cancer and invasive cervical cancer, detected incidentally during the female-to-male sex reassignment surgery. The management of these patients is presented. Such individuals may not be receiving regular gynecologic care appropriate to their remaining genital organs; symptoms of malignant disease may be missed.

  2. Elephantiasis nostras verrucosa on the abdomen of a Turkish female patient caused by morbid obesity.

    PubMed

    Buyuktas, D; Arslan, E; Celik, O; Tasan, E; Demirkesen, C; Gundogdu, S

    2010-08-15

    Elephantiasis Nostras Verrucosa is a rare disorder of an extremity or a body region, which is associated with chronic lymphedema. There are 7 reported cases of abdominal elephantiasis in the medical literature. Here we report a morbidly obese female patient with elephantiasis nostras verrucosa on the abdominal wall.

  3. Hemizygous Fabry disease associated with IgA nephropathy: a case report.

    PubMed

    Shimohata, Homare; Yoh, Keigyou; Takada, Kenji; Tanaka, Hiroaki; Usui, Joichi; Hirayama, Kouichi; Kobayashi, Masaki; Yamagata, Kunihiro

    2009-01-01

    We present a 22-year-old male patient who showed both classical Fabry disease and IgA nephropathy. He had proteinuria (1.5 g/day), hypohidrosis and neuralgia with fever. Serum creatinine and blood urea nitrogen were 0.9 mg/dL and 11.4 mg/dL, respectively. Renal biopsy showed strikingly vacuolated podocytes and tubular epithelium cells. Myelin-like bodies were detected in podocytes, mesangial cells, endothelial cells and tubular epithelium cells by electron microscopy. On immunofluorescence microscopy, IgA and C3 deposits were detected in mesangial areas. From these results and a markedly low level of alpha-galactosidase A activity, this patient was diagnosed as having classical Fabry disease and IgA nephropathy.

  4. An economic Fabry-Perot wavelength reference

    NASA Astrophysics Data System (ADS)

    Fżrész, Gábor; Glenday, Alex; Latham, Christian

    2014-07-01

    Precision radial velocity (PRV) measurements are key in studying exoplanets, and so are wavelength calibrators in PRV instruments. ThAr lamps offer an affordable but somewhat limited solution for the visible passband. Laser frequency combs are ideal calibrators, except the (still) narrow wavelength coverage and large price tag. White light Fabry-Perot (FP) calibrators offer frequency-comb like properties in a more affordable and less complicated package1. Using a commercial solid FP etalon and off-the shelf components we have constructed an economic FP calibrator suitable for observatories on a smaller budget.

  5. Sexual dysfunction, mood, anxiety, and personality disorders in female patients with fibromyalgia

    PubMed Central

    Kayhan, Fatih; Küçük, Adem; Satan, Yılmaz; İlgün, Erdem; Arslan, Şevket; İlik, Faik

    2016-01-01

    Background We aimed to investigate the current prevalence of sexual dysfunction (SD), mood, anxiety, and personality disorders in female patients with fibromyalgia (FM). Methods This case–control study involved 96 patients with FM and 94 healthy women. The SD diagnosis was based on a psychiatric interview in accordance with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. Mood and anxiety disorders were diagnosed using the Structured Clinical Interview. Personality disorders were diagnosed according to the Structured Clinical Interview for DSM, Revised Third Edition Personality Disorders. Results Fifty of the 96 patients (52.1%) suffered from SD. The most common SD was lack of sexual desire (n=36, 37.5%) and arousal disorder (n=10, 10.4%). Of the 96 patients, 45 (46.9%) had a mood or anxiety disorder and 13 (13.5%) had a personality disorder. The most common mood, anxiety, and personality disorders were major depression (26%), generalized anxiety disorder (8.3%), and histrionic personality disorder (10.4%). Conclusion SD, mood, and anxiety disorders are frequently observed in female patients with FM. Pain plays a greater role in the development of SD in female patients with FM. PMID:26937190

  6. Standards for Clinical Trials in Male and Female Sexual Dysfunction: II. Patient-Reported Outcome Measures.

    PubMed

    Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

    2016-12-01

    The second article in this series, Standards for Clinical Trials in Male and Female Sexual Dysfunction, focuses on measurement of patient-reported outcomes (PROs). Together with the design of appropriate phase I to phase IV clinical trials, the development, validation, choice, and implementation of valid PRO measurements-the focus of the present article-form the foundation of research on treatments for male and female sexual dysfunctions. PRO measurements are assessments of any aspect of a patient's health status that come directly from the patient (ie, without the interpretation of the patient's responses by a physician or anyone else). PROs are essential for assessing male and female sexual dysfunction and treatment response, including symptom frequency and severity, personal distress, satisfaction, and other measurements of sexual and general health-related quality of life. Although there are some relatively objective measurements of sexual dysfunction (ie, intravaginal ejaculatory latency time, frequency of sexual activity, etc), these measurements do not comprehensively assess the occurrence and extent of sexual dysfunction or treatment on the patient's symptoms, functioning, and well-being. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patient's perspective. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  7. Sexual dysfunction, mood, anxiety, and personality disorders in female patients with fibromyalgia.

    PubMed

    Kayhan, Fatih; Küçük, Adem; Satan, Yılmaz; İlgün, Erdem; Arslan, Şevket; İlik, Faik

    2016-01-01

    We aimed to investigate the current prevalence of sexual dysfunction (SD), mood, anxiety, and personality disorders in female patients with fibromyalgia (FM). This case-control study involved 96 patients with FM and 94 healthy women. The SD diagnosis was based on a psychiatric interview in accordance with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. Mood and anxiety disorders were diagnosed using the Structured Clinical Interview. Personality disorders were diagnosed according to the Structured Clinical Interview for DSM, Revised Third Edition Personality Disorders. Fifty of the 96 patients (52.1%) suffered from SD. The most common SD was lack of sexual desire (n=36, 37.5%) and arousal disorder (n=10, 10.4%). Of the 96 patients, 45 (46.9%) had a mood or anxiety disorder and 13 (13.5%) had a personality disorder. The most common mood, anxiety, and personality disorders were major depression (26%), generalized anxiety disorder (8.3%), and histrionic personality disorder (10.4%). SD, mood, and anxiety disorders are frequently observed in female patients with FM. Pain plays a greater role in the development of SD in female patients with FM.

  8. Dissociative symptoms in female patients with mood and anxiety disorders: a psychopathological and temperamental investigation.

    PubMed

    Bersani, G; Moscariello, M A; Bersani, F S; Colletti, C; Anastasia, A; Prinzivalli, E; Valeriani, G; Salviati, M

    2014-01-01

    Dissociative symptoms are frequent among psychiatric patients and may considerably affect patients' psychopathological condition and treatment outcomes. The objectives of the study are to assess the presence of dissociative symptoms in female patients with mood and anxiety disorders, to investigate their correlation with the clinical severity of the disorders and to investigate those personality traits that are more frequent in patients with high levels of dissociation. 50 Caucasian females were enrolled in the study. Patients were assessed through the Self-Report Symptom Check-List, the Dissociative Experiences Scale (DES) and rating scales for Depression and Anxiety. The mean DES score in the overall sample was 16.6. 32% of patients had a DES score > 20. Depressive symptoms positively correlated with the DES total scores. Dissociator patients presented some significantly different temperamental characteristics in comparison with non dissociator patients. Dissociative symptoms are highly present in patients with mood and anxiety disorders and correlate with the severity of depressive symptoms. Specific personality traits more frequently observed in dissociator people may represent predisposing factors; their early identification could be clinically relevant.

  9. Examining Patient Conceptions: A Case of Metastatic Breast Cancer in an African American Male to Female Transgender Patient

    PubMed Central

    Dhand, Amar

    2009-01-01

    An African American male to female transgender patient treated with estrogen detected a breast lump that was confirmed by her primary care provider. The patient refused mammography and 14 months later she was diagnosed with metastatic breast cancer with spinal cord compression. We used ethnographic interviews and observations to elicit the patient’s conceptions of her illness and actions. The patient identified herself as biologically male and socially female; she thought that the former protected her against breast cancer; she had fears that excision would make a breast tumor spread; and she believed injectable estrogens were less likely than oral estrogens to cause cancer. Analysis suggests dissociation between the patient’s social and biological identities, fear and fatalism around cancer screening, and legitimization of injectable hormones. This case emphasizes the importance of eliciting and interpreting a patient’s conceptions of health and illness when discordant understandings develop between patient and physician. PMID:19898907

  10. Diagnostic performance of initial serum lactate for predicting bacteremia in female patients with acute pyelonephritis.

    PubMed

    Seo, Dong Young; Jo, Sion; Lee, Jae Baek; Jin, Young Ho; Jeong, Taeoh; Yoon, Jaechol; Park, Boyoung

    2016-08-01

    The purpose of the present study was to investigate the diagnostic value of lactate for predicting bacteremia in female patients with acute pyelonephritis (APN). We conducted a retrospective study of female patients with APN who visited the study hospital emergency department. The demographics, comorbidities, physiologies, and laboratory variables including white blood cell count and segmented neutrophil count, C-reactive protein, and initial serum lactate levels were collected and analyzed to identify associations with the presence of bacteremia. During the study period, a total of 314 patients were enrolled. One hundred twenty-three patients (39.2%) had bacteremia. Escherichia coli was the most frequent pathogen. Logistic regression analysis demonstrated that the lactate level was independently associated with the presence of bacteremia (odds ratio, 1.39 [95% confidence interval, 1.08-1.78]). The C-statistic of the lactate level was 0.67 (95% CI, 0.60-0.73). At a cutoff value of 1.4mmol/L, the lactate level predicted bacteremia with a sensitivity (53.7%), specificity (72.3%), positive predictive value (55.5%), negative predictive value (70.8%), positive likelihood ratio (1.93), and negative likelihood ratio (0.64). The initial serum lactate level showed poor discriminative performance for predicting bacteremia in female patients with APN. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. A randomised, double-blinded study comparing giving etoricoxib vs. placebo to female patients with fibromyalgia.

    PubMed

    Mahagna, H; Amital, D; Amital, H

    2016-02-01

    Current therapeutic approaches to fibromyalgia syndrome (FMS) do not provide satisfactory pain control to a high percentage of patients. This unmet need constantly fuels the pursuit for new modalities for pain relief. This randomised, double-blind, controlled study assessed the efficacy and safety of adding etoricoxib vs. placebo to the current therapeutic regimen of female patients with FMS. In this double-blind, placebo-controlled study, female patients were randomised to receive either 90 mg etoricoxib once daily or placebo for 6 weeks. Several physical and mental parameters were assessed throughout the study. The primary end-point was the response to treatment, defined as ≥ 30% reduction in the average Brief Pain Inventory score. Secondary outcomes were changes in the Fibromyalgia Impact Questionnaire, SF-36 Quality of Life assessment questionnaire and Hamilton rating scales for anxiety and depression. Overall, 73 patients were recruited. Although many outcome measures improved throughout the study, no difference was recorded between the etoricoxib- and placebo-treated groups. The Brief Pain Inventory, Fibromyalgia Impact Questionnaire, The Hamilton Anxiety and Depression scores did not differ between the two groups. This is the first randomised, double-blind study assessing the effect of adding etoricoxib to pre-existing medications for female patients with FMS. Although being mildly underpowered this study clearly has shown that etoricoxib did not improve pain scores and did not lead to any beneficial mental or physical effects. © 2016 John Wiley & Sons Ltd.

  12. Prospective study of depression and anxiety in female fertility preservation and infertility patients.

    PubMed

    Lawson, Angela K; Klock, Susan C; Pavone, Mary Ellen; Hirshfeld-Cytron, Jennifer; Smith, Kristin N; Kazer, Ralph R

    2014-11-01

    To prospectively assess anxiety, depression, coping, and appraisal in female fertility preservation (FP) patients compared with infertile patients. Prospective pre- and post-treatment survey. Academic medical center. Forty-seven women with cancer (FP patients) and 91 age-matched infertile patients. None. Depression, anxiety, coping, infertility-related stress, appraisal of treatment, and medical outcomes. FP patients reported more symptoms of anxiety and depression than infertile patients, but infertile patients' symptoms worsened over time; 44% of FP and 14% of infertile patients' scores exceeded the clinical cutoff for depression before treatment. The interval between surveys and medical treatment data did not predict changes in mood symptoms. Coping strategies and infertility-related stress did not differ between groups, and avoidant coping predicted higher depression and anxiety scores. FP patients reported more anxiety and depression than infertile patients at enrollment in treatment, with more than one-third of FP patients reporting clinically significant depressive symptoms. However, infertile patients' anxiety and depressive symptoms increased across treatment. This increase was not related to time between registration for IVF and oocyte retrieval or the medical aspects of treatment. FP and infertile patients should be provided psychologic consultation before treatment to identify mood and anxiety symptoms and to refer patients for counseling as needed to prevent worsening of symptoms. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Serum adipocytokine profile and metabolic syndrome in young adult female dermatomyositis patients.

    PubMed

    Silva, Marilda Guimarães; Borba, Eduardo Ferreira; Mello, Suzana Beatriz Veríssimo de; Shinjo, Samuel Katsuyuki

    2016-12-01

    To analyse the frequency of metabolic syndrome in young adult female dermatomyositis patients and its possible association with clinical and laboratory dermatomyositis-related features and serum adipocytokines. This cross-sectional study included 35 dermatomyositis patients and 48 healthy controls. Metabolic syndrome was defined according to the 2009 Joint Interim Statement. Patient age was comparable in the dermatomyositis and control groups, and the median disease duration was 1.0 year. An increased prevalence of metabolic syndrome was detected in the dermatomyositis group (34.3% vs. 6.3%; p=0.001). In addition, increased serum adiponectin and resistin levels were noted in contrast to lower leptin levels. In dermatomyositis patients, adipocytokine levels were correlated with the levels of total cholesterol, low-density cholesterol, triglycerides and muscle enzymes. A comparison of dermatomyositis patients with (n=12) and without (n=23) syndrome metabolic revealed that adipocytokine levels were also correlated with age, and that dermatomyositis patients with metabolic syndrome tended to have more disease activity despite similar adipocytokine levels. Metabolic syndrome is highly prevalent in young adult female dermatomyositis patients and is related to age and disease activity. Moreover, increased serum adiponectin and resistin levels were detected in dermatomyositis patients, but lower serum leptin levels were observed.

  14. Serum adipocytokine profile and metabolic syndrome in young adult female dermatomyositis patients

    PubMed Central

    Silva, Marilda Guimarães; Borba, Eduardo Ferreira; de Mello, Suzana Beatriz Veríssimo; Shinjo, Samuel Katsuyuki

    2016-01-01

    OBJECTIVES: To analyse the frequency of metabolic syndrome in young adult female dermatomyositis patients and its possible association with clinical and laboratory dermatomyositis-related features and serum adipocytokines. METHOD: This cross-sectional study included 35 dermatomyositis patients and 48 healthy controls. Metabolic syndrome was defined according to the 2009 Joint Interim Statement. RESULTS: Patient age was comparable in the dermatomyositis and control groups, and the median disease duration was 1.0 year. An increased prevalence of metabolic syndrome was detected in the dermatomyositis group (34.3% vs. 6.3%; p=0.001). In addition, increased serum adiponectin and resistin levels were noted in contrast to lower leptin levels. In dermatomyositis patients, adipocytokine levels were correlated with the levels of total cholesterol, low-density cholesterol, triglycerides and muscle enzymes. A comparison of dermatomyositis patients with (n=12) and without (n=23) syndrome metabolic revealed that adipocytokine levels were also correlated with age, and that dermatomyositis patients with metabolic syndrome tended to have more disease activity despite similar adipocytokine levels. CONCLUSIONS: Metabolic syndrome is highly prevalent in young adult female dermatomyositis patients and is related to age and disease activity. Moreover, increased serum adiponectin and resistin levels were detected in dermatomyositis patients, but lower serum leptin levels were observed. PMID:28076515

  15. De novo SHANK3 mutation causes Rett syndrome-like phenotype in a female patient.

    PubMed

    Hara, Munetsugu; Ohba, Chihiro; Yamashita, Yushiro; Saitsu, Hirotomo; Matsumoto, Naomichi; Matsuishi, Toyojiro

    2015-07-01

    Rett syndrome (RTT) is a neurodevelopmental disorder predominantly affecting females. Females with the MECP2 mutations exhibit a broad spectrum of clinical manifestations ranging from classical Rett syndrome to asymptomatic carriers. Mutations of genes encoding cyclin-dependent kinase-like 5 (CDKL5) and forkhead box G1 (FOXG1) are also found in early onset RTT variants. Here, we present the first report of a female patient with RTT-like phenotype caused by SHANK3 (SH3 and multiple ankylin repeat domain 3) mutation, indicating that the clinical spectrum of SHANK3 mutations may extend to RTT-like phenotype in addition to (severe) developmental delay, absence of expressive speech, autistic behaviors and intellectual disability.

  16. Mortality 6 years after inpatient treatment of female Japanese patients with eating disorders associated with alcoholism.

    PubMed

    Suzuki, Kenji; Takeda, Aya; Yoshino, Aihide

    2011-06-01

    This study was conducted to clarify the mortality of patients with eating disorders associated with alcoholism. We focused on the mortality rate 6 years after inpatient treatment of patients with eating disorders associated with alcoholism compared with eating disorder patients without alcoholism and alcoholic patients without eating disorders. The subjects were 164 female Japanese patients 30 years of age or younger with eating disorders or alcoholism who were inpatients at some time during the period from 1990 to 1998 at the Japanese National Hospital Organization, Kurihama Alcoholism Center. A semi-structured interview concerning alcohol problems, eating problems, psychiatric disorders and other clinical characteristics was conducted at the time of the first admission. A survey concerning survival was conducted in October 2001, and 100% of the patients were followed up. The mortality of the 47 eating disorder patients with alcoholism, 86 eating disorder patients without alcoholism, and 31 alcoholics without eating disorders was 27.7%, 3.5%, and 19.4%, respectively, at 6 years after inpatient treatment, showing significant differences. On the Kaplan-Meier survival curves, the mortality of the eating disorder patients with alcoholism was significantly higher than that of the patients without alcoholism, but not significantly higher than that of young female alcoholics without eating disorders. The 13 eating disorder patients with alcoholism who had died were five anorexia nervosa and seven bulimia nervosa patients. The results of the study suggest that comorbid alcoholism is a major factor in the death of anorexia nervosa and bulimia nervosa patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

  17. Acute Myocardial Infarction due to Polyarteritis Nodosa in a Young Female Patient.

    PubMed

    Wi, Jin; Choi, Hyun Hee; Lee, Chan Joo; Kim, Taehoon; Shin, Sanghoon; Ko, Young-Guk; Jang, Yangsoo; Park, Yong Bum; Kwon, Young Joo

    2010-04-01

    Coronary artery aneurysms are uncommon, are usually associated with atherosclerosis, and rarely involve all three major coronary arteries. The present report describes a rare case of a young female patient presenting with acute myocardial infarction (AMI). Coronary angiography revealed multiple severe aneurysmal and stenotic changes. Based on clinical feature and angiographic findings, it was strongly suspected that the patient had polyarteritis nodosa (PAN) complicated by AMI. The patient was treated with standard cardiac medications and immunosuppressive agents and has remained stable without further complications during a follow-up period of 6 months.

  18. Oral Spironolactone in Post-teenage Female Patients with Acne Vulgaris

    PubMed Central

    Kim, Grace K.

    2012-01-01

    Oral spironolactone has been used for over two decades in the dermatological setting. Although it is not generally considered a primary option in the management of female patients with acne vulgaris, the increase in office visits by post-teenage women with acne vulgaris has recently placed a spotlight on the use of this agent in this subgroup of patients. This article reviews the literature focusing on the use of oral spironolactone in this subset of women with acne vulgaris, including discussions of the recommended starting dose, expected response time, adjustments in therapy, potential adverse effects, and patient monitoring. PMID:22468178

  19. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

    PubMed Central

    2011-01-01

    Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be

  20. Low Serum Urate Levels Are Associated to Female Gender in Multiple Sclerosis Patients

    PubMed Central

    Zoccolella, Stefano; Tortorella, Carla; Iaffaldano, Pietro; Direnzo, Vita; D’Onghia, Mariangela; Luciannatelli, Elena; Paolicelli, Damiano; Livrea, Paolo; Trojano, Maria

    2012-01-01

    Background Urate is a natural antioxidant and may prevent CNS tissue damage and the clinical manifestations of experimental autoimmune encephalitis. Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain. Objective To evaluate serum urate levels in MS patients and their relationships with clinical, demographic and MRI variables. Methods Levels of non-fasting serum uric acid and creatinine were determined by an automated enzymatic assay and glomerular filtration rate was assessed in 245 MS patients, in 252 age/sex-matched neurological controls (NC) and in 59 Healthy controls (HC). Results Median serum urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02), whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5 mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL), compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR ≤2: 3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female sex (beta: −0.53; p<0.00001) was the most significant determinant of serum urate concentrations in MS patients on multivariate regression analysis. Conclusions Our findings suggest that low urate levels could be of significance in predominantly inflammatory phases of MS even at the early stage and mainly in females. PMID:22848387

  1. Relation of burden of myocardial fibrosis to malignant ventricular arrhythmias and outcomes in Fabry disease.

    PubMed

    Krämer, Johannes; Niemann, Markus; Störk, Stefan; Frantz, Stefan; Beer, Meinrad; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2014-09-15

    The aim of this study was to investigate the impact of myocardial fibrosis in Fabry disease. Seventy-three patients with genetically confirmed Fabry disease were followed for 4.8 ± 2.4 years. In accordance with current guidelines, 57 patients received enzyme replacement therapy (ERT) after study inclusion, whereas 16 did not. At baseline and latest possible follow-up, myocardial fibrosis was assessed noninvasively by cardiac magnetic resonance, and biomarkers of collagen metabolism were determined. Holter electrocardiography and clinical follow-up at yearly intervals were used to monitor malignant ventricular arrhythmias (MVAs; nonsustained and sustained ventricular tachycardia and sudden cardiac death). In total, 48 patients (66%) showed fibrosis assessed by late enhancement (LE) at baseline, and 4 patients developed new LE during follow-up, 2 of them despite ERT. The 2 patients receiving ERT (1.4 ± 1.9% vs 2.5 ± 2.6%, p <0.001) and the patients not receiving ERT (0.5 ± 0.8% vs 0.7 ± 1.0%, p = 0.035) showed a progression of LE during follow-up. None of the patients displayed reductions of LE during follow-up. Collagen biomarkers were elevated in patients with and without LE but did not correlate with LE amount. Thirteen LE-positive patients at the baseline examination had documented MVAs (including 5 sudden cardiac deaths), whereas none of the patients without LE had MVAs. The yearly increase in fibrosis was 0.9 ± 0.6% in patients with MVAs and 0.2 ± 0.3% in patients without MVAs (p <0.001). Logistic multivariate regression analysis revealed that the annual increase in fibrosis during follow-up was the only independent predictor of MVAs. In conclusion, myocardial fibrosis in Fabry disease is progressive, apparently not modified by ERT, and a crucial outcome determinant.

  2. Reproducibility and genital sparing with a vaginal dilator used for female anal cancer patients.

    PubMed

    Briere, Tina Marie; Crane, Christopher H; Beddar, Sam; Bhosale, Priya; Mok, Henry; Delclos, Marc E; Krishnan, Sunil; Das, Prajnan

    2012-08-01

    Acute vulvitis, acute urethritis, and permanent sexual dysfunction are common among patients treated with chemoradiation for squamous cell carcinoma of the anal canal. Avoidance of the genitalia may reduce sexual dysfunction. A vaginal dilator may help delineate and displace the vulva and lower vagina away from the primary tumor. The goal of this study was to evaluate the positional reproducibility and vaginal sparing with the use of a vaginal dilator. Ten female patients treated with IMRT for anal cancer were included in this study. A silicone vaginal dilator measuring 29 mm in diameter and 114 mm in length was inserted into the vagina before simulation and each treatment. The reproducibility of dilator placement was investigated with antero-posterior and lateral images acquired daily. Weekly cone beam CT (CBCT) imaging was used to confirm coverage of the GTV, which was typically posterior and inferior to the dilator apex. Finally, a planning study was performed to compare the vaginal doses for these 10 patients to a comparable group of 10 female patients who were treated for anal cancer with IMRT without vaginal dilators. The absolute values of the location of the dilator apex were 7.0 ± 7.8mm in the supero-inferior direction, 7.5 ± 5.5 mm in the antero-posterior, and 3.8 ± 3.1mm in the lateral direction. Coverage of the GTV and CTV was confirmed from CBCT images. The mean dose to the vagina was lower by 5.5 Gy, on average, for the vaginal dilator patients, compared to patients treated without vaginal dilators. The vaginal dilator tended to be inserted more inferiorly during treatment than during simulation. For these ten patients, this did not compromise tumor coverage. Combined with IMRT treatment planning, use of a vaginal dilator could allow for maximum sparing of female genitalia for patients undergoing radiation therapy for anal cancer. Published by Elsevier Ireland Ltd.

  3. AIB1 Genomic Amplification Predicts Poor Clinical Outcomes in Female Glioma Patients

    PubMed Central

    Chen, Lihong; Wang, Changwei; Zhang, Xinyuan; Gao, Ke; Liu, Rui; Shi, Bingyin; Hou, Peng

    2016-01-01

    Amplified in breast cancer 1 (AIB1) gene, a coactivator for steroid receptor, is frequently amplified in diverse cancers and is considered as an oncogene in tumorigenesis. However, the prognostic significance of AIB1 amplification in gliomas remains totally unclear. In this study, 115 gliomas and 16 benign meningiomas as control subjects were enrolled, and the copy number of AIB1 was analyzed in these samples. In addition, we explored potential correlation of AIB1 amplification with clinicopathological characteristics and clinical outcomes of glioma patients. Our data showed that glioma samples exhibited a significantly higher AIB1 copy number than control subjects as determined by quantitative polymerase chain reaction (qPCR) approach. Moreover, univariate analysis showed that AIB1 amplification (≥3.5 copies) was strongly correlated with cancer-related death (P =0.03). Interestingly, our data revealed a significant association of AIB1 amplification with WHO grade (P =0.03), tumor recurrence (P =0.03) and survival status (P =0.03) in female patients but not in male patients. Multivariate analysis further demonstrated that AIB1 amplification was independent factor for cancer-related death in female patients. Importantly, AIB1 amplification was closely relevant to worse survival in female patients (P =0.001), but not in male patients (P =1.00). In addition, the patients with AIB1 amplification were resistant to radiotherapy. Altogether, our data demonstrate that AIB1 amplification is a common genetic event in glioma tumorigenesis, and suggest that AIB1 amplification is not only a prognostic factor for poor clinical outcomes in glioma patients, but also a predictor of radiotherapy resistance in gliomas. PMID:27877220

  4. Sexual harassment of female physicians by patients. What is to be done?

    PubMed Central

    Phillips, S.

    1996-01-01

    OBJECTIVE: To determine the responses of female physicians who have been sexually harassed by patients, as a means of answering the question, "What is to be done?" DESIGN: As part of a larger study on the topic, randomly selected participants were mailed a questionnaire requesting information about the nature and extent of sexual harassment by patients and about resulting feelings, actions, and suggestions for prevention. SETTING: Family practices in Ontario. PARTICIPANTS: A random sample of the 1064 female certificants of the College of Family Physicians of Canada in active practice in Ontario during 1992 was selected. A total of 599 were surveyed; 422 (70%) replied. MAIN OUTCOME MEASURES: Responses to survey questions. RESULTS: Of the 422 respondents, 76% reported sexual harassment by patients and their reactions to it. Though most respondents had many suggestions about how to minimize harassment, written comments suggested confusion as to its cause. Many participants wondered whether their behaviour, manner, or dress provoked unwanted responses. The ability to root the cause of the harassment externally as a social rather than a personal problem seemed to decrease immobilization. CONCLUSIONS: There is no single effective response to sexual harassment, but understanding its source as an abuse of the power of gender* (perhaps to overcome the powerlessness felt as a patient) could enable female physicians to act in protective and effective ways. PMID:8924816

  5. [Control study for muscle force and component of body of female patients with knee osteoarthritis].

    PubMed

    Pang, Jian; Cao, Yue-long; Shi, Yin-yu; Zhou, Ji-wei; Wang, Xiang; Shi, Ying

    2008-11-01

    To understand the information of female patients with knee osteoarthritis regarding muscle force, constitution parameter. Thirty-seven cases diagnosed as knee osteoarthritis and 37 controls were examined by MES. T-test was used to analysis two groups differences of muscle force, constitution parameter, et al. Compared between affected limbs and controls limbs in patients revealed that the lower limb muscle distribution index of the affected limbs was higher than the control limbs (P<0.05), but comparison in functional status the lower limb muscle force, muscle functional index and muscle force of unit volume of the affected limbs were lower than the control limbs (P<0.05). Compared between patients group and control group the muscle force of both lower limbs, muscle functional index and muscle force of unit volume were lower than control group (P<0.001). The utility muscle force of lower limbs of female patients with knee osteoarthritis is weaker than healthy female. Muscle function disorder instead of muscle atrophy is the key cause of the weakness.

  6. Combined Application of Ultrasound and CT Increased Diagnostic Value in Female Patients with Pelvic Masses.

    PubMed

    Liu, Yan; Zhang, Hui; Li, Xiaoqian; Qi, Guiqin

    2016-01-01

    Purpose. The current study aimed to evaluate whether combined application of ultrasound and CT had increased Diagnostic Value in Female Patients with Pelvic Masses over either method alone. Patients and Methods. 240 female patients with pelvic masses were detected preoperatively with ultrasound and CT prior to surgery. The sensitivity, specificity, and accuracy of ultrasound, CT, and combined ultrasound/CT application were evaluated, respectively. Results. The sensitivity, specificity, and accuracy of ultrasound were 52.8%, 86.7%, and 68.75%, respectively. The sensitivity, specificity, and accuracy of CT were 80.3%, 90.3%, and 85%, respectively. The sensitivity, specificity, and accuracy of combined application of ultrasound and CT were 89%, 94.7%, and 91.7%. The sensitivity, specificity, and accuracy of combined application of ultrasound and CT were higher than those of either ultrasound or CT. Conclusions. The combined application of ultrasound and CT had higher Diagnostic Value in Female Patients with Pelvic Masses than either method alone.

  7. Alteration of prolactin serum levels during alcohol withdrawal correlates with craving in female patients.

    PubMed

    Hillemacher, Thomas; Bayerlein, Kristina; Wilhelm, Julia; Reulbach, Udo; Frieling, Helge; Bönsch, Dominikus; Kornhuber, Johannes; Bleich, Stefan

    2005-12-01

    Dopaminergic transmission has been suggested to be a main mechanism mediating reinforcement, withdrawal and craving in alcohol dependency. Dopamine is associated with prolactin secretion, acting as a prolactin inhibitor. The aim of the present study was to investigate whether there is an association between altered prolactin levels and craving during early and late alcohol withdrawal. Therefore, we examined 145 patients suffering from alcohol dependency after admission to the detoxification unit, assessing craving with the Obsessive Compulsive Drinking Scale (OCDS) and measuring prolactin serum levels during early withdrawal (-EW: day 0 or day 1) and late withdrawal (-LW: day 7-day 10). We observed a significant influence of the alteration of prolactin during withdrawal on craving in female patients (Spearman's rho, OCDS-EW: r=-0.607, p=0.001; OCDS-LW: r=-0.730, p<0.001; n=26). The association between prolactin alteration in percentage and craving in females was confirmed with general linear models (OCDS-EW: F=15.819, p=0.001, r(2)=0.530; OCDS-LW: F=17.091, p<0.001, r(2)=0.535). In male patients we did not find any significant results. Our findings support the previously described role of the hypothalamic-pituitary-adrenal (HPA) axis in the neurobiology of alcohol craving and show evidence of an association between increased prolactin serum levels and lower craving during alcohol withdrawal in female patients.

  8. Combined Application of Ultrasound and CT Increased Diagnostic Value in Female Patients with Pelvic Masses

    PubMed Central

    Liu, Yan; Zhang, Hui; Li, Xiaoqian

    2016-01-01

    Purpose. The current study aimed to evaluate whether combined application of ultrasound and CT had increased Diagnostic Value in Female Patients with Pelvic Masses over either method alone. Patients and Methods. 240 female patients with pelvic masses were detected preoperatively with ultrasound and CT prior to surgery. The sensitivity, specificity, and accuracy of ultrasound, CT, and combined ultrasound/CT application were evaluated, respectively. Results. The sensitivity, specificity, and accuracy of ultrasound were 52.8%, 86.7%, and 68.75%, respectively. The sensitivity, specificity, and accuracy of CT were 80.3%, 90.3%, and 85%, respectively. The sensitivity, specificity, and accuracy of combined application of ultrasound and CT were 89%, 94.7%, and 91.7%. The sensitivity, specificity, and accuracy of combined application of ultrasound and CT were higher than those of either ultrasound or CT. Conclusions. The combined application of ultrasound and CT had higher Diagnostic Value in Female Patients with Pelvic Masses than either method alone. PMID:27867419

  9. A Case of Behcet’s Disease Combined with Pulmonary Artery Aneurysm in a Korean Female Patient

    PubMed Central

    Uh, Sootaek; Kim, Jin Oh; You, Yong Kyu; Moon, Seung Hyug; Park, Choon Sik

    1994-01-01

    Behcet’s disease (BD) is a systemic disorder of unknown process resulting from systemic vasculitis. The pulmonary involvements in BD are uncommon. Furthermore, in the female, involvement of the pulmonary artery is quite rare. There were a few cases of female patients with BD with pulmonary artery aneurysm confirmed by pulmonary artery angiogram. In this article, we report a case of BD, combined with pulmonary artery aneurysm, confirmed by pulmonary angiogram and treated by surgery in a Korean female patient. PMID:8038147

  10. Exercise increases serum endostatin levels in female and male patients with diabetes and controls

    PubMed Central

    2014-01-01

    Background Type 2 diabetes mellitus (T2DM) is often associated with atherosclerotic changes in coronary vessels, most notably plaques. The angiostatic parameter endostatin is able to inhibit angiogenesis in tissue as well as in plaques and therefore plays an important role in physiological and pathological neovascularisation. The aim of the present study was to investigate sex-specific differences and the influence of exercise on circulating endostatin levels in patients suffering from diabetes, and control subjects. Methods In total, 42 T2DM-patients and 45 control subjects were investigated. They underwent a graded physical stress test (ergometry). Serum endostatin levels were measured in venous blood at rest and directly after reaching maximum workload. Results Females showed significantly higher endostatin levels at baseline measurements compared to men, independently of their underlying disease. In both female and male T2DM-patients endostatin levels were significantly lower compared to controls. Both groups and sexes showed a significant increase of endostatin after physical stress, whereas the extent of endostatin-increase was between 10.59-15.05%. Conclusion Middle-aged healthy female individuals as well as female T2DM-patients showed higher circulating serum endostatin levels compared to males, suggesting a hormonal influence on baseline circulating endostatin amounts. Exercise-induced increase in endostatin is also observable in patients suffering from T2DM. Concerning vascularisation, lower endostatin levels in T2DM might be advantageous. Concerning plaque stability, lower levels might be prejudicial. Trial registration Clinical Trial Registration-URL: http://clinicaltrials.gov/ct2/results?term=NCT01165515 PMID:24393402

  11. Quality of Life and Migraine Disability among Female Migraine Patients in a Tertiary Hospital in Malaysia

    PubMed Central

    Shaik, Munvar Miya; Hassan, Norul Badriah; Gan, Siew Hua

    2015-01-01

    Background. Disability caused by migraine may be one of the main causes of burden contributing to poor quality of life (QOL) among migraine patients. Thus, this study aimed to measure QOL among migraine sufferers in comparison with healthy controls. Methods. Female diagnosed migraine patients (n= 100) and healthy controls (n=100) completed the Malay version of the World Health Organization QOL Brief (WHOQOL-BREF) questionnaire. Only migraine patients completed the Malay version of the Migraine Disability Assessment questionnaire. Results. Females with migraines had significantly lower total WHOQOL-BREF scores (84.3) than did healthy controls (91.9, P<0.001). Similarly, physical health (23.4 versus 27.7, P<0.001) and psychological health scores (21.7 versus 23.2, P< 0.001) were significantly lower than those for healthy controls. Seventy-three percent of patients experienced severe disability, with significantly higher number of days with headaches (13.8 days/3 months, P< 0.001) and pain scores (7.4, P< 0.013). Furthermore, migraine patients with lower total QOL scores had 1.2 times higher odds of having disability than patients with higher total QOL scores. Conclusions. The present study showed that migraine sufferers experienced significantly lower QOL than the control group from a similar population. Disability was severe and frequent and was associated with lower QOL among the migraine patients. PMID:25632394

  12. Successful pregnancy in a female patient with congenital chloride diarrhea (CLD) and renal impairment.

    PubMed

    Shimizu, Yoshio; Kamoda, Tomohiro; Nagata, Michio; Yoh, Keigyo; Hashimoto, Yuko; Matsui, Akira; Yoshikawa, Hiroyuki; Yamagata, Kunihiro; Koyama, Akio

    2009-01-01

    We report a successful case of pregnancy in a female patient with congenital chloride diarrhea (CLD) and reduced renal function due to interruption of treatment. CLD is an autosomal recessive disorder of intestinal electrolyte absorption caused by mutations in the solute carrier family 26, member 3 (SLC26A3) gene, and continuous production of watery diarrhea induces dehydration, metabolic alkalosis and many kinds of electrolyte disturbances in CLD patients. The patient in our case was a 24-year-old female CLD patient with moderate renal impairment; a renal biopsy specimen showed minimal glomerular changes, but tubulointerstitial damage by crystal formation, consistent with renal function data. One year after our initial examination and reinstitution of therapy, the patient got married and soon conceived. There were no major problems during the course of pregnancy, and the patient successfully delivered a healthy full-term infant vaginally. The symptoms and clinical course of the patient were particularly mild, and we discuss possible reasons for these observations from a perspective of genotype, phenotype and environmental conditions.

  13. MALDI-TOF and cluster-TOF-SIMS imaging of Fabry disease biomarkers

    NASA Astrophysics Data System (ADS)

    Touboul, David; Roy, Sandrine; Germain, Dominique P.; Chaminade, Pierre; Brunelle, Alain; Laprevote, Olivier

    2007-02-01

    Fabry disease is an X-linked disorder of glycosphingolipid metabolism, in which a partial or total deficiency of [alpha]-galactosidase A, a lysosomal enzyme, results in the progressive accumulation of neutral glycosphingolipids (globotriaosylceramide and digalactosylceramide) in most fluids and tissues of the body. Few information is available about the composition and distribution in tissues of the accumulated glycosphingolipids species. Mass spectrometry imaging is an innovative technique, which can provide pieces of information about the distribution of numerous biological compounds, such as lipids, directly on the tissue sections. MALDI-TOF and cluster-TOF-SIMS imaging approaches were used to study the localization of lipids (cholesterol, cholesterol sulfate, vitamin E, glycosphingolipids ...) on skin and kidney sections of patients affected by the Fabry disease. Numerous information on pathophysiology were enlightened by both techniques.

  14. Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease.

    PubMed

    Shin, Youn-Jeong; Jeon, Yeo Jin; Jung, Namhee; Park, Joo-Won; Park, Hae-Young; Jung, Sung-Chul

    2015-10-01

    Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the α-galactosidase A (α-Gal A) lysosomal enzyme, which results in globotriaosylceramide (Gb3) storage in vascular endothelial cells and different cell types throughout the body. Involvement of the kidney and heart is life threatening, and fibrosis of these organs is considered to be involved in the pathogenesis of Fabry disease. An increased concentration of deacylated Gb3 (lyso‑Gb3) in the plasma of symptomatic patients has also been suggested as a causative molecular event. To elucidate the molecular mechanisms involved in renal fibrosis in Fabry disease, the present analyzed the changes in global gene expression prior to and following Gb3 or lyso‑Gb3 treatment in two types of kidney cell lines, human proximal renal tubular epithelial (HK‑2) and mouse renal glomerular mesangial (SV40 MES 13) cells. Gb3 and lyso‑Gb3 treatment regulated the expression of 199 and 328 genes in each cell type, demonstrating a >2.0‑fold change. The majority of the biological functions of the regulated genes were associated with fibrogenesis or epithelial‑mesenchymal transition (EMT). The gene expression patterns of sphingolipid‑treated HK‑2 cells were distinguishable from the patterns in the SV40 MES 13 cells. Several genes associated with the EMT were selected and evaluated further in kidney cells and in Fabry mouse kidney tissues. In the SV40 MES 13 cells, the DLL1, F8, and HOXA11 genes were downregulated, and FOXP2 was upregulated by treatment with Gb3 or lyso‑Gb3. In the HK‑2 cells, the ADAMTS6, BEST1, IL4, and MYH11 genes were upregulated. Upregulation of the FOXP2, COL15A1, IL4, and MYH11 genes was also observed in the Fabry mouse kidney tissues. The gene expression profiles in kidney cells following the addition of Gb3 or lyso‑Gb3 revealed substrate‑specific and cell‑specific patterns. These findings suggested that Gb3 and lyso‑Gb3 lead to renal

  15. E-Learning for Rare Diseases: An Example Using Fabry Disease.

    PubMed

    Cimmaruta, Chiara; Liguori, Ludovica; Monticelli, Maria; Andreotti, Giuseppina; Citro, Valentina

    2017-09-24

    Rare diseases represent a challenge for physicians because patients are rarely seen, and they can manifest with symptoms similar to those of common diseases. In this work, genetic confirmation of diagnosis is derived from DNA sequencing. We present a tutorial for the molecular analysis of a rare disease using Fabry disease as an example. An exonic sequence derived from a hypothetical male patient was matched against human reference data using a genome browser. The missense mutation was identified by running BlastX, and information on the affected protein was retrieved from the database UniProt. The pathogenic nature of the mutation was assessed with PolyPhen-2. Disease-specific databases were used to assess whether the missense mutation led to a severe phenotype, and whether pharmacological therapy was an option. An inexpensive bioinformatics approach is presented to get the reader acquainted with the diagnosis of Fabry disease. The reader is introduced to the field of pharmacological chaperones, a therapeutic approach that can be applied only to certain Fabry genotypes. The principle underlying the analysis of exome sequencing can be explained in simple terms using web applications and databases which facilitate diagnosis and therapeutic choices.

  16. Isolation and characterization of microsatellite loci in Quercus fabri (Fagaceae).

    PubMed

    Xiao, Z Z; Chen, W W; Bao, W; Wang, R; Li, Y Y

    2016-06-21

    Quercus fabri is a pioneer species of secondary succession in evergreen broadleaved forests in China. In this study, we isolated and developed 12 polymorphic and 2 monomorphic microsatellite loci for Q. fabri using the biotin-streptavidin capture method. We characterized 12 polymorphic loci in 52 individuals from two populations. The number of alleles per locus ranged from 3 to 23. The observed and expected heterozygosities per locus were 0.033-0.773 and 0.138-0.924, respectively. These microsatellite loci will facilitate the studies on genetic variation, mating system, and gene flow of Q. fabri.

  17. Involvement of dorsal root ganglia in Fabry's disease.

    PubMed

    Gadoth, N; Sandbank, U

    1983-08-01

    Bouts of shooting pain along the extremities are common in the early stages of Fabry's disease. No pathological explanation has been advanced to clarify the mechanism of such pain. In the present case neuronal storage of glycolipid was confined to dorsal root ganglia neurones only. It is suggested that this may explain the shooting pain in Fabry's disease. In hereditary sensory radicular neuropathy, familial dysautonomia, and tabes dorsalis, changes in dorsal root ganglia cells cause similar clinical signs and thus it may be concluded that shooting pains in Fabry's disease may be caused by damage to dorsal root ganglia neurones.

  18. Involvement of dorsal root ganglia in Fabry's disease.

    PubMed Central

    Gadoth, N; Sandbank, U

    1983-01-01

    Bouts of shooting pain along the extremities are common in the early stages of Fabry's disease. No pathological explanation has been advanced to clarify the mechanism of such pain. In the present case neuronal storage of glycolipid was confined to dorsal root ganglia neurones only. It is suggested that this may explain the shooting pain in Fabry's disease. In hereditary sensory radicular neuropathy, familial dysautonomia, and tabes dorsalis, changes in dorsal root ganglia cells cause similar clinical signs and thus it may be concluded that shooting pains in Fabry's disease may be caused by damage to dorsal root ganglia neurones. Images PMID:6413695

  19. Serum levels of metal ions in female patients with breast cancer.

    PubMed

    Pavithra, V; Sathisha, T G; Kasturi, K; Mallika, D Siva; Amos, S Jeevan; Ragunatha, S

    2015-01-01

    Breast cancer is the second commonest form of cancer among women. Several studies have been conducted to identify potential risk factors. However, role of trace elements or metals in causing breast cancer has not been studied to great extent. To estimate the serum levels of calcium, copper, magnesium, iron, phosphorus and zinc and determine their role in causing breast cancer in female patients. A case-control study on female patients with breast cancer was conducted in a private superspecialty hospital and Cancer centre situated in Southern part of India. Newly diagnosed female patients with breast cancer in the age group of 30-60 y attending Oncology clinic were included in the study. These cases were selected irrespective of type and stage of the disease. The age matched control subjects were drawn from apparently healthy women attending master health check at superspecialty hospital. The patients or controls suffering from co-morbid conditions which affect serum levels of metal ions and other malignancies, and those undergoing treatment for breast cancer were excluded from the study. Serum was separated and tests were performed according to standard procedure for each metal ion on the same day. The estimation of metal ions was done by UV-Visible Spectrophotometer-CHEM 7. Independent Samples T-test was used to calculate difference between the two means. The p-value of <0.05 was considered as significant. The study was conducted on 54 female patients with breast cancer and 54 female controls with mean age of 47.2±8.14 y and 46.8±8.4 y respectively. There was statistically significant increase in serum levels of calcium, copper, iron and phosphorus in patients with breast cancer when compared to controls. The increase in serum levels of magnesium was insignificant. A statistically significant decrease in serum zinc levels was observed in patient with breast cancer when compared to controls. The present study highlights the role of calcium, copper, iron

  20. Transaxillary Subpectoral Placement of Cardiac Implantable Electronic Devices in Young Female Patients

    PubMed Central

    Oh, Joo Hyun; Kim, Chae Min; Song, Seung Yong; Uhm, Jae Sun; Lew, Dae Hyun

    2017-01-01

    Background The current indications of cardiac implantable electronic devices (CIEDs) have expanded to include young patients with serious cardiac risk factors, but CIED placement has the disadvantage of involving unsightly scarring and bulging of the chest wall. A collaborative team of cardiologists and plastic surgeons developed a technique for the subpectoral placement of CIEDs in young female patients via a transaxillary approach. Methods From July 2012 to December 2015, subpectoral CIED placement via an axillary incision was performed in 10 young female patients, with a mean age of 25.9 years and mean body mass index of 20.1 kg/m2. In the supine position, with the patient's shoulder abducted, an approximately 5-cm linear incision was made along one of the deepest axillary creases. The submuscular plane was identified at the lateral border of the pectoralis major, and the dissection continued over the clavipectoral fascia until the subpectoral pocket could securely receive a pulse generator. Slight upward dissection also exposed an entrance to the subclavian vein, allowing the cardiology team to gain access to the vein. One patient with dilated cardiomyopathy underwent augmentation mammoplasty and CIED insertion simultaneously. Results One case of late-onset device infection occurred. All patients were highly satisfied with the results and reported that they would recommend the procedure to others. Conclusions With superior aesthetic outcomes compared to conventional methods, the subpectoral placement of CIEDs via a transaxillary approach is an effective, single-incision method to hide operative scarring and minimize bulging of the device, and is particularly beneficial for young female or lean patients. PMID:28194345

  1. FISH analysis of a subtle familial Xp deletion in a female patient with Madelung deformity

    SciTech Connect

    Hsu, T.Y.; Gibson, L.H.; Pober, B.R.

    1994-09-01

    A subtle deletion of Xp [del(X)(p22.32)]was identified by high-resolution chromosome analysis in a twelve-year-old female with short stature (<2 percentile) and Madelung deformity suggestive of Turner syndrome. The proband`s mother, who has short stature (<2 percentile) and demyelinating disorder, also showed this deletion. The maternal grandmother is of normal height and carries two normal X chromosomes. Both the patient and her mother have no other physical abnormalities and are of normal intelligence. To confirm and delineate this Xp deletion, fluorescence in situ hybridization (FISH) was performed on metaphases from the patient and her mother using probes of DXYS20 (a pseudoautosomal locus), DXS232A, and a newly isolated Xp YAC clone, YHX2, whose relative map position is unknown. Hybridization signals of DXS232A were detected on both X chromosomes, and DXYS20 and YHX2 were missing from one of the X`s of both the patient and her mother. YHX2 was thus placed distal to DXS232A (tel-DXYS20-YHX2-S232A-cen). This familial deletion with a breakpoint distal to DXS232A, which is located at -900 Kb telomeric to STS locus, appears to be the smallest Xp deletion reported thus far. Short stature is consistently associated with females carrying Xp deletions. Madelung deformity has been found in some patients with Turner syndrome or Dyschondrosteosis but it has not been reported in patients with Xp deletion. Our results suggest that the phenotype of our patient is associated with her chromosome abnormality. Due to the subtlety of the deletion identified in our patient and her mother, females presenting with short stature warrant careful clinical and cytogenetic evaluation.

  2. Fabry disease in children and the effects of enzyme replacement treatment.

    PubMed

    Pintos-Morell, Guillem; Beck, Michael

    2009-11-01

    Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a deficiency in the activity of the lysosomal enzyme, alpha-galactosidase A. In affected patients, the enzyme substrate, globotriaosylceramide (Gb3), accumulates in cells of various tissues and organs. Lysosomal accumulation of Gb3 begins in utero, and signs and symptoms of Fabry disease emerge in childhood and adolescence. The earliest presenting symptoms are typically neuropathic pain and gastrointestinal problems, which can have a substantial impact on health-related quality of life. Life-threatening major organ involvement is rare in young patients, but signs of kidney dysfunction (e.g., proteinuria), left ventricular hypertrophy, and stroke have been reported in children. There are two enzyme preparations for therapy: agalsidase alfa and beta. In two clinical trials of enzyme replacement therapy (ERT) with agalsidase alfa, including 37 children, boys demonstrated reductions in plasma Gb3 levels, and both boys and girls reported reductions in neuropathic pain and in the use of neuropathic pain medications. Heart rate variability, which is reduced in boys with Fabry disease, was statistically significantly improved with 6 months of agalsidase alfa treatment. In a single clinical study of agalsidase beta in children (n =16), skin Gb3 deposits and plasma Gb3 levels were reduced in boys. Differences exist in the administration and the safety profile of these two enzyme formulations. Follow-up of these cohorts and additional studies will be necessary to fully evaluate long-term efficacy of ERT in children with Fabry disease.

  3. Increased expression of Trpv1 in peripheral terminals mediates thermal nociception in Fabry disease mouse model

    PubMed Central

    Lakomá, Jarmila; Rimondini, Roberto; Ferrer Montiel, Antonio; Donadio, Vincenzo; Liguori, Rocco

    2016-01-01

    Fabry disease is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (α-GalA) enzyme. α-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3) in the endothelium and vascular smooth muscles. A hallmark symptom of Fabry disease patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. The α-GalA gene null mouse model (α-GalA(−/0)) has provided molecular evidence for the molecular alterations in small type-C nociceptors in Fabry disease that may underlie their hyperexcitability, although the specific mechanism remains elusive. Here, we have addressed this question and report that small type-C nociceptors from α-GalA(−/0) mice exhibit a significant increase in the expression and function of the TRPV1 channel, a thermoTRP channel implicated in painful heat sensation. Notably, male α-GalA(−/0) mice displayed a ≈2-fold higher heat sensitivity than wild-type animals, consistent with the augmented expression levels and activity of TRPV1 in α-GalA(−/0) nociceptors. Intriguingly, blockade of neuronal exocytosis with peptide DD04107, a process that inhibits among others the algesic membrane recruitment of TRPV1 channels in peptidergic nociceptors, virtually eliminated the enhanced heat nociception of α-GalA(−/0) mice. Together, these findings suggest that the augmented expression of TRPV1 in α-GalA(−/0) nociceptors may underly at least in part their increased heat sensitivity, and imply that blockade of peripheral neuronal exocytosis may be a valuable pharmacological strategy to reduce pain in Fabry disease patients, increasing their quality of life. PMID:27531673

  4. [Clinical and laboratory features of pheochromocytoma in a 52-year-old female patient].

    PubMed

    Aranguren, Otmara; Mora, Idania Teresa; Cardosa, Maritza; León, Olga; López, María Victoria; Portales, Ramón

    2014-04-22

    The article aims to describe the clinical and laboratory features of a female patient suffering from pheochromocytoma. The case is a 52-year-old female patient who presents to our healthcare center with high blood pressure, cold limbs, sweating, jitteriness, and episodes of oppressive chest pain that appear several times per day. She also reports fatigue and a 13-kilogram weight loss. The sonogram revealed a nodular image in the right adrenal gland that had low echogenicity and regular margins measuring 5 mm. The image was confirmed with a contrast-enhanced adrenal CAT scan. Urine vanillylmandelic acid levels were high and an adrenal biopsy confirmed a pheochromocytoma measuring 4.5 x 3.5 x 3 cm.

  5. Prolactin levels and autoantibodies in female patients with systemic lupus erythematosus.

    PubMed

    Kozáková, D; Rovenský, J; Cebecauer, L; Bosák, V; Jahnová, E; Vigas, M

    2000-01-01

    We investigated the relationships between prolactin (PRL) levels and antibody occurrence in systemic lupus erythematosus (SLE). No significant association between PRL levels and the majority of the autoantibodies studied (anti-U1 RNP, anti-rRNP, anti-Sm, anti-dsDNA, anti-DNP, auto-LCA, anti-EACA) could be confirmed (P > 0.05), anti-Ro/SSA antibodies being an exception. Our results showed significantly increased frequencies of these antibodies in the group of female SLE patients with normal PRL levels (< 20 micrograms/L): anti Ro/SSA in 53% (P < 0.025, chi 2 = 5.80, RR = 4.0) and anti-Ro/SSA + anti-Ro/La in 60% (P < 0.05, chi 2 = 4.05) compared with female SLE patients with hyperprolactinemia.

  6. Efficacy of Self-Hypnosis in Pain Management in Female Patients with Multiple Sclerosis.

    PubMed

    Hosseinzadegan, Fariba; Radfar, Moloud; Shafiee-Kandjani, Ali Reza; Sheikh, Naser

    2017-01-01

    Pain is common in patients with multiple sclerosis. This study evaluated self-hypnosis for pain control in that population. A randomized clinical trial was conducted on 60 patients, who were assigned to either a control group or to a self-hypnosis group, in which patients performed self-hypnosis at least 10 times a day. All patients were trained to score the perceived pain twice daily on a numerical rating scale and also reported the quality of pain with the McGill Pain questionnaire. Repeated-measures analysis showed a significant difference between the groups; pain was lower in the self-hypnosis group but was not maintained after 4 weeks. Self-hypnosis could effectively decrease the intensity and could modify quality of pain in female patients with multiple sclerosis.

  7. Low-frequency electrotherapy for female patients with detrusor underactivity due to neuromuscular deficiency.

    PubMed

    Xu, Dan-Feng; Zhang, Shen; Wang, Cun-Zhou; Li, Jun; Qu, Chuang-Yu; Cui, Xin-Gang; Zhao, Sheng-Jia

    2012-08-01

    The aim of the study was to assess the efficacy of low-frequency electrotherapy (LFE) for female patients with early-stage detrusor underactivity (DUA) due to neuromuscular deficiency. A total of 102 female patients were divided randomly into four groups: LFE-NC (normal compliance), LFE-LC (low compliance), CON (control)-NC and CON-LC. Patients in the LFE-NC and LFE-LC groups received LFE, and those in the CON-NC and CON-LC groups received conservative treatment. Urodynamic evaluation was performed before and after treatment. After treatment, 82 % of the LFE-NC regained detrusor contractility, whereas only 2 (8 %) of the CON-NC had normal detrusor contraction. None of LFE-LC or CON-LC regained detrusor contractility (p < 0.01). The per cent of LFE-NC who relied on catheterization for bladder emptying decreased by 43 % (p < 0.01). Those in the LFE-LC, CON-NC and CON-LC groups decreased by only 4, 12 or 0 % (p > 0.05). LFE was more effective for DUA patients with normal compliance; these patients benefited from LFE, but DUA patients with low compliance did not.

  8. Defaecography and colonic transit time for the evaluation of female patients with obstructed defaecation.

    PubMed

    Cosentino, Maria; Beati, Claudio; Fornari, Simona; Capalbo, Emanuela; Peli, Michela; Lovisatti, Maria; Cariati, Maurizio; Cornalba, Gianpaolo

    2014-11-01

    Colonic transit time and defaecography are well known, commonly used studies for evaluating patients with chronic constipation. The aim of this study was to compare colonic transit time with radiopaque markers and defaecography in female patients with obstructed defaecation. In a prospective observational study, between January 2010 and December 2012, a total of 30 female patients, mean age 60 years, with symptoms of obstructed defaecation were subjected to colonic transit time and defaecography, and divided into two groups: normal or abnormal colon transit time. The results were statistically compared using the Chi-square test. The comparison of data between colonic transit time and defaecography showed the following groups: group 1 (6/30 = 20 %) with normal colonic transit time but abnormal defaecography, and group 2 (24/30 = 80 %) with abnormal colonic transit time; the latter was further divided into two subgroups: group 2a (4/24 = 17 %), patients with inertia coli; group 2b (20/24 = 83 %), patients with impaired defaecation demonstrated at defaecography. There was a significant statistical difference between the radiological findings in these groups. This study confirmed the value of both defaecography and colonic transit time in assessing clinically obstructed women. Obstructed defaecation might not always be associated with abnormal colonic transit time. Likewise, not all constipated patients had signs of obstructed defaecation. The differential diagnosis between colonic slow transit constipation and constipation due to pelvic floor disorders is essential for an adequate strategy of care.

  9. Occurrence of epidermolysis bullosa along with Amelogenesis imperfecta in female patient of India.

    PubMed

    Javed, A P; Shenai, Prashanth; Chatra, Laxmikanth; Veena, K M; Rao, Prasanna Kumar; Prabhu, Rachana

    2013-11-01

    Epidermolysis bullosa (EB) is an inherited disorder, which is characteristically presented as skin blisters developing in response to minor injury. Junctional variety of EB is also associated with enamel hypoplasia. Amelogenesis imperfecta presents with abnormal formation of the enamel both in deciduous and permanent dentition. This article describes a previously unreported case of Amelogenesis imperfecta with complete loss of enamel in a young female patient with EB.

  10. Determinants of sexual disability and dissatisfaction in female patients with rheumatoid arthritis.

    PubMed

    Abdel-Nasser, Ahmed M; Ali, Essam I

    2006-11-01

    Previous research has identified two main problems of sexuality in female rheumatoid arthritis (RA) patients: difficulties in sexual performance and diminution of sexual desire and satisfaction. This study attempts to determine the clinical and psychological factors significantly contributing to sexual disability and dissatisfaction in female RA patients. Ninety consecutive female RA outpatients were assessed by a gynecologist. After excluding patients who were not sexually active and those with genital tract abnormalities, 52 patients were examined and investigated rheumatologically and given questionnaires assessing sexual performance, desire, and satisfaction, as well as demographic variables, pain, disability, anxiety, and depression. Following a correlation analysis, the contributions of demographic, disease, and psychological variables to sexual disability and dissatisfaction were explored by hierarchical and stepwise regression. Thirty-two patients (62%) had difficulties in sexual performance including nine patients (17%) who were totally unable to engage in sexual intercourse because of arthritis. Sexual desire or satisfaction were diminished in 24 patients (46%) and completely lost in 24 patients (46%). Sexual disability was not significantly correlated with any psychodemographic variables, but with parameters of disease activity (p<0.001), Health Assessment Questionnaire (HAQ)-disability (p<0.001), hip (p<0.001) but not knee joint disease, seropositivity (p<0.05), and diminished desire (p<0.05). However, HAQ-disability and hip joint disease were the only independent and significant determinants of sexual disability in the regression model after controlling for the effects of age and disease duration. These variables together explained 64% of the variance of sexual disability. On the other hand, pain (p<0.001), age (p<0.05), and depression (p<0.05) were the significant determinants in the regression model for sexual dissatisfaction, all together

  11. Pap test use is lower among female-to-male patients than non-transgender women.

    PubMed

    Peitzmeier, Sarah M; Khullar, Karishma; Reisner, Sari L; Potter, Jennifer

    2014-12-01

    A paucity of empirical research to date has examined cervical cancer screening in female-to-male (FTM) transgender men who retain their natal reproductive structures compared to non-transgender women. To examine patient and provider characteristics associated with being up-to-date on Pap tests, with a focus on gender identity and sexual orientation. Retrospective chart review of 5,232 patients (4,882 women, 350 FTM transgender men) at an urban community health center. All HIV-negative primary care patients aged 21-64 years (inclusive) with at least one medical visit during the 2012 calendar year and who had a cervix as of December 31, 2012, were included. Data were analyzed in 2013 using a multilevel logistic regression model nesting patients within providers. FTM patients were significantly less likely to be up-to-date on Pap tests (AOR=0.63, 95% CI=0.47, 0.85) compared to non-transgender women, after adjusting for individual- and provider-level factors. Behaviorally bisexual patients, compared to patients who had sex with men exclusively, were more likely to be up-to-date (AOR=1.73, 95% CI=1.32, 2.26); patients reporting only sex with women were not significantly more or less likely to be up-to-date (AOR=1.01, 95% CI=0.83, 1.23). Transgender patients are not accessing the same level of preventive cervical screening care as non-transgender female patients. There is a need to better understand barriers to care in this population. Contrary to findings in other settings, history of sex with women was not negatively associated with Pap utilization. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Gender Identity and Gender Role in DSD Patients Raised as Females: A Preliminary Outcome Study.

    PubMed

    Ercan, Oya; Kutlug, Seyhan; Uysal, Omer; Alikasifoglu, Mujgan; Inceoglu, Derya

    2013-01-01

    Gender identity and gender role are expected to be consistent with gender assignment for optimal DSD management outcome. To our knowledge, our study is the first to attempt evaluation of gender related outcomes in Turkish DSD patients. After receiving institutional ethical board approval and subject (or parent) informed consent, subjects with DSD raised as girls (22 patients 46 XX DSD, 11 patients 46 XY DSD) answered 566 questions of the Minnesota Multiphasic Personality Inventory (MMPI) questionnaire including 60-item Masculinity-Femininity (MF) subscale which was the focus in this study. Controls (n: 50) were females similar to the probands in age, level of education, relationship status, and having a job or not also answered all questions. The answers were evaluated by a trained psychologist (Derya Inceoglu) on MMPI. For statistical purposes, seven findings were obtained from the data related to the MF subscale from the patients and controls. Of these seven findings (S1-S7), two were associated with masculinity (S3-S4) and another two were associated with femininity (S5-S6). In DSD patients, the percentages of masculinity findings were significantly higher when compared to controls (p < 0.001 and p < 0.001 for S3 and S4, respectively). In controls, the percentages of femininity findings were significantly higher when compared to DSD females (p < 0.001 and p < 0.001 for S5 and S6 respectively). There was no significant difference between 46 XX DSD patients and 46 XY DSD patients with respect to the percentage of any of the seven findings. Two patients requested gender change to male; only these two patients had the finding stating that sexual impulses could come to existence as actions (S7). In conclusion efforts to identify modifiable factors with negative impact and thus modifying them, and professional guidance may be important in minimizing the encountered gender related problems in DSD patients.

  13. Comparison of coronary plaque subtypes in male and female patients using 320-row MDCTA.

    PubMed

    Khosa, Faisal; Khan, Atif N; Nasir, Khurram; Bedayat, Arash; Malik, Zehra; Jon, Ali F; Cheema, Ahmad R; Clouse, Melvin E; Welty, Francine K

    2013-02-01

    Determine plaque subtype and volume difference in male and female patients with obstructive and non-obstructive CAD using 320-row MDCTA. 128 patients with suspected CAD underwent MDCTA. All studies were divided into two groups based on disease severity. 0-70% stenosis (non-obstructive CAD) & >70% (obstructive). All were compared for plaque quantity and subtypes by gender. Main arteries, RCA, LM, LAD and LCX were analyzed using Vitrea 5.2 software to quantify fatty, fibrous and calcified plaque. Thresholds for coronary plaque quantification (volume in mm(3)) were preset at 35 ± 12 HU for fatty, 90 ± 24 HU for fibrous and >130 HU for calcified/mixed plaque and analyzed using STATA software. Total plaque burden in 118 patients [65M: 53F] was significantly higher in all arteries in males compared to females with non-obstructive disease. Total plaque volume for males vs. females was: RCA: 10.10 ± 5.02 mm(3) vs. 6.89 ± 2.75 mm(3), respectively, p = 0.001; LAD: 7.21 ± 3.38 mm(3) vs. 5.89 ± 1.93 mm(3), respectively, p = 0.04; LCX: 9.13 ± 3.27 mm(3) vs. 7.16 ± 1.73 mm(3), respectively, p = 0.002; LM 15.13 ± 4.51 mm(3) vs. 11.85 ± 4.03 mm(3), respectively, p = 0.001. In sub-analyses, males had significantly more fibrous and fatty plaque in LM, LAD & LCX than females. However in the RCA, only fibrous plaque was significantly greater in males. Calcified plaque volume was not significantly different in both genders. Only 8% of patients had obstructive CAD (>70% stenosis); there was no significant difference in plaque volume or subtypes. In patients with non-obstructive CAD, males were found to have significantly higher total coronary plaque volume with predominance of fibrous and fatty subtypes compared to females of the same age and BMI. There was no significant difference in plaque subtype or volume in patients with obstructive disease. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients

    PubMed Central

    Levenson, Amy E.; Haas, Mary E.; Miao, Ji; Brown, Rebecca J.; de Ferranti, Sarah D.; Muniyappa, Ranganath

    2016-01-01

    Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5–23 y) with sc metreleptin injections (∼4.4 mg/d) for 4–6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r2 = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol. PMID:26824363

  15. Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients.

    PubMed

    Levenson, Amy E; Haas, Mary E; Miao, Ji; Brown, Rebecca J; de Ferranti, Sarah D; Muniyappa, Ranganath; Biddinger, Sudha B

    2016-04-01

    Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5-23 y) with sc metreleptin injections (∼4.4 mg/d) for 4-6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r(2) = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol.

  16. Decreased functional connectivity density in pain-related brain regions of female migraine patients without aura.

    PubMed

    Gao, Qing; Xu, Fei; Jiang, Cui; Chen, Zhifeng; Chen, Huafu; Liao, Huaqiang; Zhao, Ling

    2016-02-01

    Migraine is one of the most prevalent neurological disorders which is suggested to be associated with dysfunctions of the central nervous system. The purpose of the present study was to detect the altered functional connectivity architecture in the large-scale network of the whole brain in migraine without aura (MWoA). Meanwhile, the brain functional hubs which are targeted by MWoA could be identified. A new voxel-based method named functional connectivity density (FCD) mapping was applied to resting-state functional magnetic resonance imaging data of 55 female MWoA patients and 44 age-matched female healthy controls (HC). Comparing to HC, MWoA patients showed abnormal short-range FCD values in bilateral hippocampus, bilateral insula, right amygdale, right anterior cingulate cortex, bilateral putamen, bilateral caudate nucleus and the prefrontal cortex. The results suggested decreased intraregional connectivity of these pain-related brain regions in female MWoA. In addition, short-range FCD values in left prefrontal cortex, putamen and caudate nucleus were significantly negatively correlated with duration of disease in MWoA group, implying the repeated migraine attacks over time may consistently affect the resting-state functional connectivity architecture of these brain hubs. Our findings revealed the dysfunction of brain hubs in female MWoA, and suggested the left prefrontal cortex, putamen and caudate nucleus served as sensitive neuroimaging markers for reflecting the disease duration of female MWoA. This may provide us new insights into the changes in the organization of the large-scale brain network in MWoA. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Adrenocortical response to low-dose ACTH test in female patients with rheumatoid arthritis.

    PubMed

    Radikova, Zofia; Rovensky, Jozef; Vlcek, Miroslav; Penesova, Adela; Kerlik, Jana; Vigas, Milan; Imrich, Richard

    2008-12-01

    Alterations in adrenal steroid production have been suggested in females with rheumatoid arthritis (RA). The aim of the present study was to assess adrenocortical function in RA females. We examined 11 female RA patients (RA: age 30 +/- 2 years, BMI 21.0 +/- 0.7 kg/m(2)) and 10 matched healthy controls (C: age 31 +/- 1 years, BMI 21.6 +/- 0.6 kg/m(2)). Low-dose adrenocorticotropic hormone (ACTH) test (i.v. bolus of 1 microg synthetic ACTH) was performed at 10.00 h with blood sampling every 15 min for 90 min. Cortisol, 17-OH-progesterone (17OHP), androstenedione (ASD), and dehydroepiandrosterone (DHEA) were assayed in plasma. Baseline cortisol levels were higher in RA patients (RA: 385 +/- 38 versus C: 229 +/- 28 nmol/L, P= 0.007). In both study groups, ACTH administration increased all the four steroids measured (P < 0.001). Cortisol response to ACTH administration was diminished in RA patients when compared to controls (Delta(max): 284 +/- 24 in RA versus 424 +/- 31 nmol/L in C, P= 0.002). ACTH-induced maximal rise in plasma DHEA was significantly lower in RA patients when compared to controls (Delta(max): 2.59 +/- 0.68 in RA versus 5.57 +/- 1.25 ng/mL in C, P= 0.015). No significant between-groups differences were found in responses of ASD or 17OHP. The molar ratio of ASD:cortisol was significantly lower (P < 0.05) in RA patients at base line, but did not differ during ACTH test. After ACTH bolus, the cortisol:17OHP ratio decreased significantly in the RA group (P < 0.001), whereas there was no change in the control group. The present results show decreased secretion of cortisol and DHEA in RA patients in response to ACTH, suggesting a subtle HPA hypofunction at the adrenocortical level.

  18. Diagnostic dilemmas in Fabry disease: a case series study on GLA mutations of unknown clinical significance.

    PubMed

    Smid, B E; Hollak, C E M; Poorthuis, B J H M; van den Bergh Weerman, M A; Florquin, S; Kok, W E M; Lekanne Deprez, R H; Timmermans, J; Linthorst, G E

    2015-08-01

    Fabry disease' (FD) phenotype is heterogeneous: alpha-galactosidase A gene mutations (GLA) can lead to classical or non-classical FD, or no FD. The aim of this study is to describe pitfalls in diagnosing non-classical FD and assess the diagnostic value of plasma globotriaosylsphingosine. This is a case series study. Family 1 (p.A143T) presented with hypertrophic cardiomyopathy (HCM), absent classical FD signs, high residual alpha-galactosidase A activity (AGAL-A) and normal plasma globotriaosylsphingosine. Co-segregating sarcomeric mutations were found. Cardiac biopsy excluded FD. In family 2 (p.P60L), FD was suspected after kidney biopsy in a female with chloroquine use. Males had residual AGAL-A, no classical FD signs and minimally increased plasma globotriaosylsphingosine, indicating that p.P60L is most likely non-pathogenic. Non-specific complications and histology can be explained by chloroquine and alternative causes. Males of two unrelated families (p.R112H) show AGAL-A <5%, but slightly elevated plasma globotriaosylsphingosine (1.2-2.0 classical males >50 nmol/l). Histological evidence suggests a variable penetrance of this mutation. Patients with GLA mutations and non-specific findings such as HCM may have non-classical FD or no FD. Other (genetic) causes of FD-like findings should be excluded, including medication inducing FD-like storage. Plasma globotriaosylsphingosine may serve as a diagnostic tool, but histology of an affected organ is often mandatory. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Fabry-Perot resonance of water waves.

    PubMed

    Couston, Louis-Alexandre; Guo, Qiuchen; Chamanzar, Maysamreza; Alam, Mohammad-Reza

    2015-10-01

    We show that significant water wave amplification is obtained in a water resonator consisting of two spatially separated patches of small-amplitude sinusoidal corrugations on an otherwise flat seabed. The corrugations reflect the incident waves according to the so-called Bragg reflection mechanism, and the distance between the two sets controls whether the trapped reflected waves experience constructive or destructive interference within the resonator. The resulting amplification or suppression is enhanced with increasing number of ripples and is most effective for specific resonator lengths and at the Bragg frequency, which is determined by the corrugation period. Our analysis draws on the analogous mechanism that occurs between two partially reflecting mirrors in optics, a phenomenon named after its discoverers Charles Fabry and Alfred Perot.

  20. Optically addressed asymmetric Fabry-Perot modulator

    NASA Technical Reports Server (NTRS)

    Larsson, A.; Maserjian, J.

    1991-01-01

    A low power, high contrast optically addressed modulator, operating with normal incidence, has been fabricated. Optically controlled reflection modulation is achieved through optically induced absorption modulation in a periodically delta-doped InGaAs/GaAs multiple quantum well structure inserted in an integrated asymmetric Fabry-Perot resonator. A contrast ratio over 60:1 was measured using a spectrally matched low power InGaAs/GaAs quantum well laser to generate the write (control) signal. The insertion loss for the normally off modulator is 4.6 dB at the highest write signal power (30 mW) used. The device lends itself to the fabrication of arrays for optically addressed spatial light modulation.

  1. Modeling of Fabry-Perot collection optics

    SciTech Connect

    Frank, A.M.

    1984-07-16

    The purpose of these calculations was to determine whether the collection optics of the Fabry-Perot velocimeter could be improved by conversion to a relay system. In this study the optical design code ACCOS5 was used to model both the current system and a relay. The ACCOS5 printouts are given. Spot diagrams of 1000 rays each were computed from four locations for each of the two configurations. These include source points on axis and 150 ..mu..m off axis for the system both in focus and with the object advanced 40 mm towards the objective. The back focus (BF) of both systems is optimized by the program for best paraxial focus. The distance was then fixed for the 40 mm defocused case.

  2. Fabry-Perot resonance of water waves

    NASA Astrophysics Data System (ADS)

    Couston, Louis-Alexandre; Guo, Qiuchen; Chamanzar, Maysamreza; Alam, Mohammad-Reza

    2015-10-01

    We show that significant water wave amplification is obtained in a water resonator consisting of two spatially separated patches of small-amplitude sinusoidal corrugations on an otherwise flat seabed. The corrugations reflect the incident waves according to the so-called Bragg reflection mechanism, and the distance between the two sets controls whether the trapped reflected waves experience constructive or destructive interference within the resonator. The resulting amplification or suppression is enhanced with increasing number of ripples and is most effective for specific resonator lengths and at the Bragg frequency, which is determined by the corrugation period. Our analysis draws on the analogous mechanism that occurs between two partially reflecting mirrors in optics, a phenomenon named after its discoverers Charles Fabry and Alfred Perot.

  3. The Malus Fabry-Perot interferometer

    NASA Astrophysics Data System (ADS)

    Vallet, M.; Bretenaker, F.; Le Floch, A.; Le Naour, R.; Oger, M.

    1999-09-01

    We describe a general model for the behaviour of a sensor based on a Fabry-Perot interferometer placed between crossed polarizers. Compared to single-pass polarimeters, the sensitivity for the measurement of intracavity anisotropies is shown to be enhanced by a factor of the order of the square of the finesse compared to single-pass polarimeters. Our model, based on a vectorial spatial description of the cavity, predicts the response of the system to circular and/or linear intracavity anisotropies. It also gives the ultimate sensitivity and takes into account the spurious backgrounds. Experimental illustrations are presented for different types of reciprocal and non-reciprocal anisotropies. Moreover, it is shown that the insertion of an optical bias combined with a modulation of the intracavity anisotropies leads to experimental sensitivities limited only by the shot noise level, in agreement with theoretical predictions. We discuss further improvements and potential applications for the polarimeter.

  4. Therapeutic experience with oral finasteride for androgenetic alopecia in female-to-male transgender patients.

    PubMed

    Moreno-Arrones, O M; Becerra, A; Vano-Galvan, S

    2017-10-01

    Androgenic treatment of female-to-male transgender patients may result in androgenetic alopecia (AGA). Use of 5-alpha-reductase inhibitors are useful as oral treatment of AA in men. There are no previous studies of the use of finasteride in transgender men as treatment of AGA. To evaluate the effectiveness and safety of an oral 5α-reductase inhibitor (finasteride) for AA developed in transgender men. This single-centre retrospective study enrolled female-to-male transgender patients with a clinical diagnosis of AGA to receive 1 mg of an oral type II 5α-reductase inhibitor for at least 12 months. In all, 10 patients were included in the study. All the patients received a clinical diagnosis of male-pattern AGA, with 90% classified as stage IV on the Norwood-Hamilton scale. Mean onset of AGA was 3.25 years after the introduction of androgenic treatment, and 70% of the patients had a family history of AGA. All the patients improved one grade on the Norwood-Hamilton scale after a mean of 5.5 months (range 4-6 months) since the start of finasteride treatment. Two patients stopped treatment for economic reasons and one stopped due to dyspepsia. No sexual or other adverse effects were observed. Patients were given periodic physical and analytical examinations by endocrinologists without any significant finding. Mean follow-up of patients was 16.2 months. AA in transgender men has a delayed onset, and is clinically and therapeutically similar to the common male-pattern-AGA in cis-gender men. © 2017 British Association of Dermatologists.

  5. Body positions and movement patterns in female patients with congenital adrenal hyperplasia.

    PubMed

    Dittmann, R W

    1992-12-01

    Female patients with congenital adrenal hyperplasia (CAH; N = 33; 11-41 years), simple-virilizing (SV) patients (N = 19), salt-wasting (SW) patients (N = 13), and sister controls (N = 14) were compared with regard to their body positions and movement patterns. Data collection comprised both self assessments and mothers' assessments using 20 sex-dimorphic items with corresponding "more masculine" and "more feminine" versions for each variable, represented in photographs (forced-choice approach). Primarily based on mothers' assessments, single-item results suggested slightly more masculine positions and patterns for female CAH patients compared to sisters, for SW patients more distinct than for SV patients. Results from an 11-item scale ("motor behavior", alpha = 0.59) revealed differences between SW (more masculine) and SV patients for self assessments (P, one-tailed, < 0.09); sisters were in an intermediate position closer to the SV patients. According to mothers' assessments, the CAH patient group as a whole differed (more masculine) from sisters (P < 0.06); this finding was mainly accounted for by the SW group (P < 0.04). Complex analyses on the relationship of motor behavior and intervening variables (e.g., postnatal androgenization, onset of puberty, menarche, height, weight, sexual orientation) revealed very few significant results. Findings rather suggested organizational hormonal effects on body positions and movements prenatally; they are in line with main results from the interview section of the Hamburg CAH study (e.g., "Gender-related behavior"). An approach of this kind seems to be justified for investigating motor behavior in future psychoendocrine studies.

  6. Prevalence of low phospholipid-associated cholelithiasis in young female patients.

    PubMed

    Condat, Bertrand; Zanditenas, David; Barbu, Véronique; Hauuy, Marie-Pierre; Parfait, Béatrice; El Naggar, Ahmed; Collot, Véronique; Bonnet, Joélle; Ngo, Yann; Maftouh, Anware; Dugué, Laurent; Balian, Chant; Charlier, Alain; Blazquez, Martine; Rosmorduc, Olivier

    2013-11-01

    We evaluated the prevalence of low phospholipid-associated cholelithiasis, a specific form of cholelithiasis associated with at least 2 of the 3 following criteria: first symptoms before the age of 40; intrahepatic comet tail artefacts, sludge or microlithiasis on ultrasound imaging; and recurrence of symptoms after cholecystectomy. We prospectively studied the cases of 60 consecutive female patients under 30 with symptomatic cholelithiasis. A diagnosis of low phospholipid-associated cholelithiasis was made in 14/60 patients (23%). The molecular analysis showed ABCB4 (n=4) and ABCB11 (n=4) gene mutations. Low phospholipid-associated cholelithiasis was frequently observed in non-overweight patients [13/27 (48%)], was present in most patients whose biliary symptoms occurred before the age of 18 [7/10 (70%)] and was often associated with cholangitis or acute pancreatitis [9/14 (64%), p<0.05] while "common" cholelithiasis was mainly associated with cholecystitis [16/46 (35%), p<0.05]. Nearly one quarter of the female patients under the age of 30 admitted for symptomatic cholelithiasis had low phospholipid-associated cholelithiasis; particularly if body weight was normal, the symptoms began before the age of 18 or in the presence of severe biliary complications. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. Robotic gastrectomy with transvaginal specimen extraction for female gastric cancer patients

    PubMed Central

    Zhang, Shu; Jiang, Zhi-Wei; Wang, Gang; Feng, Xiao-Bo; Liu, Jiang; Zhao, Jian; Li, Jie-Shou

    2015-01-01

    AIM: To describe the application of complete robotic gastrectomy with transvaginal specimen extraction (TVSE) for gastric cancer patients. METHODS: Between July and November 2014, eight female patients who were diagnosed with gastric adenocarcinoma underwent a TVSE following a full robot-sewn gastrectomy. According to the tumor location, the patients were allocated to two different groups; two patients received robotic total gastrectomy with TVSE and the other six received robotic distal gastrectomy with TVSE. RESULTS: Surgical procedures were successfully performed in all eight cases without conversion. The mean age was 55.3 (range, 42-69) years, and the mean body mass index was 23.2 (range, 21.6-26.0) kg/m2. The mean total operative time and blood loss were 224 (range, 200-298) min and 62.5 (range, 50-150) mL, respectively. The mean postoperative hospital stay was 3.6 (range, 3-5) d. The mean number of lymph nodes resected was 23.6 (range, 17-27). None was readmitted within 30 d of postoperation. During the follow-up, no stricture developed nor was any anastomotic leakage detected. CONCLUSION: It is possible to perform a TVSE following a full robot-sewn gastrectomy with standard D2 lymph node resection for female gastric cancer patients. PMID:26715817

  8. Breast cancer in a male-to-female transsexual patient with a BRCA2 mutation.

    PubMed

    Corman, Vinciane; Potorac, Iulia; Manto, Florence; Dassy, Sarah; Segers, Karin; Thiry, Albert; Bours, Vincent; Daly, Adrian F; Beckers, Albert

    2016-05-01

    Breast cancer is rare in male patients. Certain predisposing factors, be they genetic (e.g., BRCA2 gene mutations) or hormonal (imbalance between estrogen and androgen levels), have been implicated in male breast cancer pathophysiology. Male-to-female (MtF) transsexualism is a condition that generally involves cross-sex hormone therapy. Anti-androgens and estrogens are used to mimic the female hormonal environment and induce the cross-sex secondary characteristics. In certain situations, the change in the hormonal milieu can be disadvantageous and favor the development of hormone-dependent pathologies, such as cancer. We report a case of a MtF transgender patient who developed breast cancer after 7 years of cross-sex hormonal therapy. The patient was found to be BRCA2 positive, and suffered recurrent disease. The patient was unaware of being a member of an established BRCA2 mutation-positive kindred. This represents the first case of a BRCA2 mutation predisposing to breast cancer in a MtF transgender patient. © 2016 Society for Endocrinology.

  9. Genetic variants associated with gastrointestinal symptoms in Fabry disease

    PubMed Central

    Sestito, Simona; Nicoletti, Angela; Arbitrio, Mariamena; Guzzi, Pietro Hiram; Talarico, Valentina; Altomare, Federica; Sanseviero, Maria Teresa; Agapito, Giuseppe; Pisani, Antonio; Riccio, Eleonora; Borrelli, Osvaldo; Concolino, Daniela; Pensabene, Licia

    2016-01-01

    Gastrointestinal symptoms (GIS) are often among the earliest presenting events in Fabry disease (FD), an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A. Despite recent advances in clinical and molecular characterization of FD, the pathophysiology of the GIS is still poorly understood. To shed light either on differential clinical presentation or on intervariability of GIS in FD, we genotyped 1936 genetic markers across 231 genes that encode for drug-metabolizing enzymes and drug transport proteins in 49 FD patients, using the DMET Plus platform. All nine single nucleotide polymorphisms (SNPs) mapped within four genes showed statistically significant differences in genotype frequencies between FD patients who experienced GIS and patients without GIS: ABCB11 (odd ratio (OR) = 18.07, P = 0,0019; OR = 8.21, P = 0,0083; OR=8.21, P = 0,0083; OR = 8.21, P = 0,0083),SLCO1B1 (OR = 9.23, P = 0,0065; OR = 5.08, P = 0,0289; OR = 8.21, P = 0,0083), NR1I3 (OR = 5.40, P = 0,0191) and ABCC5 (OR = 14.44, P = 0,0060). This is the first study that investigates the relationships between genetic heterogeneity in drug absorption, distribution, metabolism and excretion (ADME) related genes and GIS in FD. Our findings provide a novel genetic variant framework which warrants further investigation for precision medicine in FD. PMID:27825144

  10. Light- and electron-microscopic histochemistry of Fabry's disease.

    PubMed Central

    Faraggiana, T.; Churg, J.; Grishman, E.; Strauss, L.; Prado, A.; Bishop, D. F.; Schuchman, E.; Desnick, R. J.

    1981-01-01

    A histochemical study was performed on light- and electron-microscopic level in a case of Fabry's disease. The patient underwent kidney transplantation for renal failure and died of heart failure 6 months later. Patient's tissues were studied at the light- and electron-microscopic levels with various embedding and staining techniques for lipids and carbohydrates. Two peroxidase-labeled lectins (from Ricinus communis and from Bandeiraea simplicifolia) known to have affinity for alpha- and beta-D-galactose, were strongly reactive with the storage material on frozen sections. The ultrahistochemical and extraction tests showed that the typical granules had a variable reactivity and morphologic characteristics in different cells, probably reflecting different composition. A small number of typical deposits were also observed in the transplanted kidney. This is the first reported case of recurrence of the storage disease in the allograft. Of interest was also the fact that the patient's blood inhibited normal alpha-galactosidase activity, suggesting a possible inhibitor-related mechanism in the pathogenesis of the recurrence. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 PMID:6786101

  11. Primary dysmenorrhea is potentially predictive for initial orthodontic pain in female patients.

    PubMed

    Ye, Rui; Wang, Sheng; Li, Yu; Wu, Ruixian; Pei, Jiao; Wang, Jue; Zhao, Zhihe

    2014-05-01

    To investigate the relationship between primary dysmenorrhea (PD) and orthodontic pain in female patients, and to test the hypothesis that the intensity and duration of orthodontic pain could be roughly predicted by severity of PD. One hundred twenty college females were enrolled and put into one of three groups-mild (Mi), moderate (Mo), or severe (S)-according to level of menstrual pain. Intensity of the orthodontic pain was measured by visual analog scale (VAS) on days 1, 2, 4, 7, 14, and 28 after archwire placement. As the intensity of orthodontic pain declined with time, the three groups demonstrated different changes during the initial week. Mi had the lowest VAS scores, whereas S possessed the highest scores. In contrast, Mo stayed in between. Significantly positive correlations were found between the severity of PD and the intensity of orthodontic pain at each time point within the first 2 weeks. In addition, though the majority of subjects reported disappearance of pain by the end of the second week in both Mi and Mo, a large proportion of females still perceived pain in S. Females with higher levels of menstrual pain tended to perceive orthodontic pain with higher intensity and more prolonged duration. Thus, PD could potentially serve as a reference to predict orthodontic pain in clinical settings.

  12. Dimensional analyses of frontal posed smile attractiveness in Japanese female patients.

    PubMed

    Hata, Kyoko; Arai, Kazuhito

    2016-01-01

    To identify appropriate dimensional items in objective diagnostic analysis for attractiveness of frontal posed smile in Japanese female patients by comparing with the result of human judgments. Photographs of frontal posed smiles of 100 Japanese females after orthodontic treatment were evaluated by 20 dental students (10 males and 10 females) using a visual analogue scale (VAS). The photographs were ranked based on the VAS evaluations and the 25 photographs with the highest evaluations were selected as group A, and the 25 photos with the lowest evaluations were designated group B. Then 12 dimensional items of objective analysis selected from a literature review were measured. Means and standard deviations for measurements of the dimensional items were compared between the groups using the unpaired t-test with a significance level of P < .05. Mean values were significantly smaller in group A than in group B for interlabial gap, intervermilion distance, maxillary gingival display, maximum incisor exposure, and lower lip to incisor (P < .05). Significant differences were observed only in the vertical dimension, not in the transverse dimension. Five of the 12 objective diagnostic items were correlated with human judgments of the attractiveness of frontal posed smile in Japanese females after orthodontic treatment.

  13. The many facets of the Fabry-Perot

    NASA Astrophysics Data System (ADS)

    Sánchez-Soto, Luis L.; Monzón, Juan J.; Leuchs, Gerd

    2016-11-01

    We address the response, both in amplitude and intensity, of a Fabry-Perot from a variety of viewpoints. These complementary pictures conspire to achieve a comprehensive and consistent theory of the operation of this system.

  14. Clinical utility of an intimate partner violence screening tool for female VHA patients.

    PubMed

    Iverson, Katherine M; King, Matthew W; Resick, Patricia A; Gerber, Megan R; Kimerling, Rachel; Vogt, Dawne

    2013-10-01

    Female Veterans are at high risk for physical, sexual, and psychological forms of intimate partner violence (IPV) victimization. This study evaluated the accuracy of a brief IPV victimization screening tool for use with female Veterans Health Administration (VHA) patients. Participants completed a paper-and-pencil mail survey that included the four-item Hurt/Insult/Threaten/Scream (HITS) and the 39-item Revised Conflict Tactics Scales (CTS-2). Operating characteristics, including sensitivity and specificity, were calculated using the CTS-2 as the reference standard for past-year IPV. Female veterans from a roster of randomly selected female patients of the New England VA Healthcare System. Women must have reported being in an intimate relationship in the past year to be included. Primary measures included the HITS (index test) and the CTS-2 (reference standard). This study included 160 women. The percentage of women who reported past-year IPV, as measured by any physical assault, sexual coercion, and/or severe psychological aggression on the CTS-2, was 28.8 %. The receiver-operator characteristic curve demonstrated that the HITS cutoff score of 6 maximizes the true positives while minimizing the false positives in this sample. The sensitivity of the optimal HITS cutoff score of 6 was 78 % (95 % CI 64 % to 88 %), specificity 80 % (95 % CI 71 % to 87 %), positive likelihood ratio 3.9 (95 % CI 2.61 to 5.76), negative likelihood ratio 0.27 (95 % CI 0.16 to 0.47), positive predictive value 0.61 (95 % CI 0.47, 0.73), and negative predictive value 0.90 (95 % CI 0.82, 0.95). For a low-burden screen, the HITS demonstrated good accuracy in detecting past-year IPV relative to the CTS-2 in a sample of female VHA patients with an optimal cutpoint of 6. The HITS may help VHA and other health-care providers detect past-year IPV and deliver appropriate care for female Veterans.

  15. Matched-pair analysis of patients with female and male breast cancer: a comparative analysis.

    PubMed

    Foerster, Robert; Foerster, Frank G; Wulff, Volkhard; Schubotz, Birgit; Baaske, Dieter; Wolfgarten, Matthias; Kuhn, Walther C; Rudlowski, Christian

    2011-08-04

    Male breast cancer (MBC) is a rare disease accounting for approximately 1% of all breast carcinomas. Presently treatment recommendations are derived from the standards for female breast cancer. However, those approaches might be inadequate because of distinct gender specific differences in tumor biology of breast cancer. This study was planned in order to contrast potential differences between female and male breast cancer in both tumor biological behavior and clinical management. MBC diagnosed between 1995-2007 (region Chemnitz/Zwickau, Saxony, Germany) was retrospectively analyzed. Tumor characteristics, treatment and follow-up of the patients were documented. In order to highlight potential differences each MBC was matched with a female counterpart (FBC) that showed accordance in at least eight tumor characteristics (year of diagnosis, age, tumor stage, nodal status, grade, estrogen- and progesterone receptors, HER2 status). 108 male/female matched-pairs were available for survival analyses. In our study men and women with breast cancer had similar disease-free (DFS) and overall (OS) survival. The 5-years DFS was 53.4% (95% CI, range 54.1-66.3) in men respectively 62.6% (95% CI, 63.5-75.3) in women (p > 0.05). The 5-years OS was 71.4% (95% CI, 62.1-72.7%) and 70.3% (95% CI, 32.6-49.6) in women (p > 0.05). In males DFS analyses revealed progesterone receptor expression as the only prognostic relevant factor (p = 0.006). In multivariate analyses for OS both advanced tumor size (p = 0.01) and a lack of progesterone receptor expression were correlated (p = 0.01) with poor patients outcome in MBC. Our comparative study revealed no survival differences between male and female breast cancer patients and gives evidence that gender is no predictor for survival in breast cancer. This was shown despite of significant gender specific differences in terms of frequency and intensity of systemic therapy in favor to female breast cancer.

  16. Fabry disease: polymorphic haplotypes and a novel missense mutation in the GLA gene.

    PubMed

    Ferri, L; Guido, C; la Marca, G; Malvagia, S; Cavicchi, C; Fiumara, A; Barone, R; Parini, R; Antuzzi, D; Feliciani, C; Zampetti, A; Manna, R; Giglio, S; Della Valle, C M; Wu, X; Valenzano, K J; Benjamin, R; Donati, M A; Guerrini, R; Genuardi, M; Morrone, A

    2012-03-01

    Fabry disease: polymorphic haplotypes and a novel missense mutation in the GLA gene. Fabry disease (FD) is an X-linked lysosomal storage disorder with a heterogeneous spectrum of clinical manifestations that are caused by the deficiency of α-galactosidase A (α-Gal-A) activity. Although useful for diagnosis in males, enzyme activity is not a reliable biochemical marker in heterozygous females due to random X-chromosome inactivation, thus rendering DNA sequencing of the α-Gal-A gene, alpha-galactosidase gene (GLA), the most reliable test for the confirmation of diagnosis in females. The spectrum of GLA mutations is highly heterogeneous. Many polymorphic GLA variants have been described, but it is unclear if haplotypes formed by combinations of such variants correlate with FD, thus complicating molecular diagnosis in females with normal α-Gal-A activity. We tested 67 female probands with clinical manifestations that may be associated with FD and 110 control males with normal α-Gal-A activity. Five different combinations of GLA polymorphic variants were identified in 14 of the 67 females, whereas clearcut pathogenetic alterations, p.Met51Ile and p.Met290Leu, were identified in two cases. The latter has not been reported so far, and both mutant forms were found to be responsive to the pharmacological chaperone deoxygalactonojirimycin (DGJ; migalastat hydrochloride). Analysis of the male control population, as well as male relatives of a suspected FD female proband, permitted the identification of seven different GLA gene haplotypes in strong linkage disequilibrium. The identification of haplotypes in control males provides evidence against their involvement in the development of FD phenotypic manifestations.

  17. Factitious proteinuria - the most dominant feature in a young female patient with Munchausen syndrome.

    PubMed

    Lela, Ivana Vuković; Karanović, Sandra; Matišić, Danica; Kuzmanić, Duško; C Orić, Marijana; Šimić, Mirjana; Jelaković, Bojan

    2013-02-01

    Munchausen syndrome is a factitious disorder with predominantly physical signs and symptoms, resulting from the patient's high motivation for assuming a sick role, without any external incentives or boundaries. We report the case of a young female patient with factitious proteinuria in the nephrotic range and a fairly eventful medical history. After performing many expensive and unnecessary investigations and procedures,the real origin of the proteinuria was determined;it was found to be caused by the patient carefully adding calibrated egg albumin to her urine samples. This discovery roused suspicions about multiple, non-corroborated conditions from her history (e.g., multiple miscarriages, breast cancer, and thyroid disorders).The diversity of diseases presented by a single Munchausen patient tends to be bizarre,and thus is a challenge for health care providers to diagnose the condition. Teamwork is therefore of the utmost necessity to diagnose Munchausen syndrome.

  18. The right ventricle in Fabry disease: natural history and impact of enzyme replacement therapy.

    PubMed

    Niemann, Markus; Breunig, Frank; Beer, Meinrad; Herrmann, Sebastian; Strotmann, Jörg; Hu, Kai; Emmert, Andrea; Voelker, Wolfram; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2010-12-01

    Storage of globotriaosylceramides is present in the left and right ventricles of patients with Fabry disease. Improvement of left ventricular morphology and function during enzyme replacement therapy (ERT) has previously been reported. To analyse the effects of long term ERT on right ventricular morphology and function. This was a prospective follow-up of 75 genetically confirmed consecutive Fabry patients for 3.1±1.8 years. According to treatment guidelines the natural history was followed in 18 patients, whereas 57 patients received ERT. Standard echocardiography, strain rate imaging for regional deformation of the right and left ventricle, and magnetic resonance tomography with late enhancement (LE) imaging for the detection of fibrosis were all performed at yearly intervals. Right ventricular hypertrophy was evident in 53 patients (71%) at baseline. A significant positive correlation was found between left and right ventricular wall thickness (r=0.76; p<0.0001). LE was detected in half of the patients (n=38) in the left ventricle at baseline while no patient ever had LE of the right ventricle. Patients with LE in the left ventricle presented with the lowest right ventricular deformation properties. In contrast to the left ventricle, there was no change in right ventricular wall thickness (baseline 6.9±1.6 mm vs follow-up 6.7±1.5 mm; p=0.44) or systolic strain rate (2.2±0.7/s vs 2.1±0.8/s; p=0.31) during follow-up with ERT. The degree of right ventricular involvement in Fabry disease is related to the left ventricular cardiomyopathy stage. ERT seems to have no direct impact on right ventricular morphology and function.

  19. Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy

    PubMed Central

    Warnock, David G; Thomas, Christie P; Vujkovac, Bojan; Campbell, Ruth C; Charrow, Joel; Laney, Dawn A; Jackson, Leslie L; Wilcox, William R; Wanner, Christoph

    2015-01-01

    Background Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) in a study of classical Fabry patients receiving recombinant agalsidase-beta therapy. Methods and design The goal was maintenance of urine protein to creatinine ratio (UPCR) <0.5 g/g or a 50% reduction in baseline UPCR for 24 patients at eight study sites. The change in estimated glomerular filtration rate (eGFR) was assessed over 21 months of treatment. Results 18 out of 24 patients achieved the UPCR goal with eGFR slopes that were significantly better than six patients who did not achieve the UPCR goal (−3.6 (−4.8 to −1.1) versus −7.0 (−9.0 to −5.6) mL/min/1.73 m2/year, respectively, p=0.018). Despite achieving the UPCR goal, 67% (12/18 patients) still progressed with an eGFR slope <−2 mL/min/1.73 m2/year. Regression analysis showed that increased age at initiation of agalsidase-beta therapy was significantly associated with worsened kidney outcome. Hypotension and hyperkalaemia occurred in seven and eight patients, respectively, which required modification of antiproteinuric therapy but was not associated with serious adverse events. Conclusions This study documents the effectiveness of agalsidase-beta (1 mg/kg/2 weeks) and antiproteinuric therapy with ACE inhibitors and/or ARB in patients with severe Fabry nephropathy. Patients had preservation of kidney function if agalsidase-beta treatment was initiated at a younger age, and UPCR maintained at or below 0.5 g/g with antiproteinuric therapy. Trial registration number NCT00446862. PMID:26490103

  20. An autocorrelator based on a Fabry-Perot interferometer.

    PubMed

    An, Jungkwuen; Pyun, Kyungsuk; Kwon, Ojoon; Kim, Dong Eon

    2013-01-14

    An autocorrelator based on a Fabry-Perot interferometer is proposed for ultrashort pulse measurement. Main features of this autocorrelator due to the superposition of multiple pulses were investigated experimentally and theoretically. It turns out that the signal from a Fabry-Perot interferometer can be used as an autocorrelator signal. This autocorrelator provides more compact setup with a much easier alignment than a conventional autocorrelator based on a Michelson interferometer.

  1. [Violent women: a multicentre study of the characteristics of female forensic psychiatric patients].

    PubMed

    de Vogel, V; Stam, J; Bouman, Y; Ter Horst, P; Lancel, M

    2014-01-01

    Violence perpetrated by women has attracted more and more attention in the past few years. However, there is lack of background information about women admitted to forensic psychiatric hospitals and about risk factors for recidivism. To conduct a multicenter study which will give more insight into female psychiatric patients and which will probably have implications for psychodiagnostics, risk assessment and treatment in (forensic) psychiatric settings. We coded the files of 297 women who, between 1984 and 2013, had been admitted to one of four Dutch forensic psychiatric facilities by reason of violent delinquent behaviour. We used an extensive coding list and several risk assessment tools including the recently developed Female Additional Manual (fam) for women. The general picture that emerged was one of severely traumatised women with complex pathology and a high level of comorbidity. Many of the women had experienced previous treatment failures and had caused many incidents during treatment. Female forensic psychiatric patients are a complex group that deserves more specific attention. Attention for traumas from the past, intensive supervision in relationships and training for staff in dealing with, for instance, manipulative behaviour are the most important implications from this study.

  2. Increased serum levels of C21 steroids in female patients with multiple sclerosis.

    PubMed

    Kanceva, R; Stárka, L; Kancheva, L; Hill, M; Veliková, M; Havrdová, E

    2015-01-01

    Multiple sclerosis (MS) is one of the most common neurological diseases. This neurodegenerative autoimmune disease manifests as inflammatory and demyelinating impairment of the central nervous system (CNS). Although some studies demonstrated associations between altered steroidogenesis and pathophysiology of MS as well as the importance of steroids in the pathophysiology of MS, the knowledge concerning the steroid metabolome in female patients is limited. Hence, 51 steroids and steroid polar conjugates were measured in the serum of 12 women with MS, untreated with steroids and 6 age-corresponding female controls with the use of gas chromatography - mass spectrometry (GC-MS). The data were processed using age adjusted ANCOVA, receiver operating characteristics (ROC) analysis and orthogonal projections to latent structures (OPLS). Our data show higher levels of circulating C21 steroids including steroid modulators of ionotropic type A gamma-aminobutyric acid (GABA A) receptors and glutamate receptors. Furthermore, the levels of GABAergic androsterone and 5-androsten-3beta,7alpha,17beta-triol were also higher in the female MS patients. In conclusion, the data demonstrate higher levels of circulating C21 steroids and their polar conjugates and some bioactive C19 steroids in women with MS, which may influence neuronal activity and affect the balance between neuroprotection and excitotoxicity.

  3. Experiences of Being Heterozygous for Fabry Disease: a Qualitative Study.

    PubMed

    von der Lippe, Charlotte; Frich, Jan C; Harris, Anna; Solbrække, Kari Nyheim

    2016-10-01

    Little is known about the experiences of women with Fabry disease. The aim of this study was to explore women's experiences of being heterozygous for Fabry disease. We used an explorative qualitative study design and selected ten Norwegian women who were known heterozygous for Fabry disease to participate. We conducted in-depth semi-structured interviews and analyzed the interviews using inductive thematic analysis. We found that learning about one's heterozygous status may be devastating for some. However, for most of the participants, heterozygous status, as well as doctors' acceptance of symptoms in women heterozygous for Fabry disease, provided an explanation and relief. Although many women did not consider themselves ill, they wished to be acknowledged as more than "just carriers." The participants were grateful for enzyme replacement therapy, although it had its burdens regarding time, planning, and absences from school or work. Women with Fabry disease felt that the lack of knowledge among healthcare professionals about Fabry disease was frustrating and worrisome. These findings suggest that healthcare professionals should acknowledge the different ways women react to their diagnosis, and be aware of the personal costs of receiving treatment.

  4. Home infusion program with enzyme replacement therapy for Fabry disease: The experience of a large Italian collaborative group.

    PubMed

    Concolino, D; Amico, L; Cappellini, M D; Cassinerio, E; Conti, M; Donati, M A; Falvo, F; Fiumara, A; Maccarone, M; Manna, R; Matucci, A; Musumeci, M B; Nicoletti, A; Nisticò, R; Papadia, F; Parini, R; Peluso, D; Pensabene, L; Pisani, A; Pistone, G; Rigoldi, M; Romani, I; Tenuta, M; Torti, G; Veroux, M; Zachara, E

    2017-09-01

    Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infusions of agalsidase alfa. For the whole cohort, the average duration of home therapy was 1 year and 11 months (range 3 months-4 years and 6 months), and during this period, compliance to treatment (number of infusions performed vs scheduled) reached 100%. The EQ-5 VAS scale was administered to patients to evaluate the self-reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up compared to baseline (home treatment start) or remaining stable. A mild increase of average disease severity, measured through Mainz Severity Score Index (MSSI), was found during hospital treatment (p < 0,007), while it remained stable between the first home therapy infusion and last follow up. Interestingly, 4 out of 7 (57%) patients, showing an improvement in FD-related clinical status after starting home therapy, had previously a sub-optimal compliance to treatment during the period of hospital treatment management. Only 4 adverse non serious reactions (0,093%) were reported totally in 2 patients during home treatment. We conclude that home infusions in eligible patients with FD are safe, contribute to improve treatment compliance and therapeutic clinical outcomes, and may have a positive impact on self-perceived QoL.

  5. Health concerns related to radiation exposure of the female nuclear medicine patient.

    PubMed Central

    Stabin, M G

    1997-01-01

    The female nuclear medicine patient is of special concern in evaluating radiation dose and risk in nuclear medicine. The female's overall body size and organ sizes generally are smaller than those of her male counterpart (thus her radiation doses will be higher, given the same amounts of administered activity and similar biokinetics); female gonads are inside the body instead of outside and are near several organs often important as source organs in internal dosimetry (urinary bladder, liver, kidneys, intestines); risk of breast cancer is significantly higher among females than males; and in the case of pregnancy, exposure to radiation of the embryo/fetus and the nursing infant are of special concern in such an analysis. All these concerns are addressed in this study through a comparative study of radiation doses for males and females over a large number (approximately 60) of nuclear medicine studies and through a study of what is known about radiation dosimetry in pregnancy and breast feeding. It was found that women's critical organ doses and effective doses (as defined by the International Commission on Radiological Protection 60 [ICRP 60] are about 25% higher than those for men across all these studies. Women's gonad doses, however, may be as much as 10 to 30 times higher than those in men, although 2- to 3-fold differences are common. Many radiopharmaceuticals are administered to women of childbearing age; however, little is known about how much activity crosses the placenta and about the biokinetics in the fetus should it occur. Nonetheless, dose estimates are provided at four stages of pregnancy (early, 3-month, 6-month, and 9-month gestation) for a large number of radiopharmaceuticals, whether or not quantitative estimates of placental crossover can be made. Many radiopharmaceuticals are also excreted in breast milk of nursing mothers. Breast feeding interruption schedules are suggested through analysis of the observed kinetics of these pharmaceuticals and

  6. Sequential occurrence of combined pulmonary fibrosis and emphysema syndrome in a non-smoker female patient.

    PubMed

    Gupta, Pawan; Dash, Devijyoti; Mittal, Richa; Chhabra, Sunil K

    2017-05-01

    The combined pulmonary fibrosis and emphysema (CPFE) syndrome is a unique and an under-recognized disorder characterized by emphysema in the upper lobes and interstitial fibrosis in the lower lobes of the lung. It occurs predominantly in males and almost exclusively in smokers. This rare combination of a restrictive and an obstructive mechanical defect carries a poorer prognosis than either of the two components. We present a case of CPFE syndrome in a non-smoker female patient who developed lower lobe emphysema subsequent to development of interstitial fibrosis. The case was remarkable for the extreme rarity of several presenting features, namely, a lower lobe occurrence of emphysema subsequent to pre-existent interstitial fibrosis, female gender and absence of a history of smoking. © 2015 John Wiley & Sons Ltd.

  7. Prevalence and Risk Factors of Sleep Disordered Breathing in Fabry disease

    PubMed Central

    Franzen, Daniel; Gerard, Nicolas; Bratton, Daniel J.; Wons, Annette; Gaisl, Thomas; Sievi, Noriane A.; Clarenbach, Christian F.; Kohler, Malcolm; Krayenbühl, Pierre A.

    2015-01-01

    Abstract Excessive daytime sleepiness (EDS) is a frequently reported and not well-understood symptom in patients with Fabry disease (FD). Sleep-disordered breathing (SDB) is a possible factor. As deposition of glycosphingolipids in the upper airway muscles is likely, we hypothesized that obstructive sleep apnoea (OSA) is highly prevalent in FD and positively associated with its severity. All patients with FD who are followed in the Fabry cohort of the University Hospital Zurich (n = 62) were asked to participate in this prospective cohort study. Eligible patients were prospectively investigated by assessing their daytime sleepiness using the Epworth Sleepiness Scale (ESS), the severity of FD using the Mainz Severity Score Index (MSSI), and by an ambulatory overnight respiratory polygraphy between November 1, 2013, and January 31, 2015. SDB was defined as an apnea/hypopnea index (AHI) of > 5/h. Fifty-two patients (mean ± SD age 42.8 ± 14.7 years, 33% men, mean ± SD BMI 23.4 ± 3.6 kg/m2) with a median (IQR) MSSI of 12 (5–19) were included. Median (IQR) ESS was 6 (2–10) and 7 patients (14%) had an ESS > 10. Thirteen patients (25%) had SDB (78% obstructive sleep apnea, 22% central sleep apnea). In the multivariable analysis, the age was the only statistically significant predictor of SDB (OR 1.11, 95% CI 1.04–1.18, P = 0.001). ESS was associated with depression (P < 0.001) but not AHI nor age. This study shows that SDB, especially obstructive sleep apnea is highly prevalent in patients with Fabry disease. However, EDS in FD seems to be related with depression rather than SDB. ClinicalTrials.gov (identifier: NCT01947634). PMID:26717401

  8. The reported sex and surgery satisfactions of 28 postoperative male-to-female transsexual patients.

    PubMed

    Rehman, J; Lazer, S; Benet, A E; Schaefer, L C; Melman, A

    1999-02-01

    From 1980 to July 1997 sixty-one male-to-female gender transformation surgeries were performed at our university center by one author (A.M.). Data were collected from patients who had surgery up to 1994 (n = 47) to obtain a minimum follow-up of 3 years; 28 patients were contacted. A mail questionnaire was supplemented by personal interviews with 11 patients and telephone interviews with remaining patients to obtain and clarify additional information. Physical and functional results of surgery were judged to be good, with few patients requiring additional corrective surgery. General satisfaction was expressed over the quality of cosmetic (normal appearing genitalia) and functional (ability to perceive orgasm) results. Follow-up showed satisfied who believed they had normal appearing genitalia and the ability to experience orgasm. Most patients were able to return to their jobs and live a more satisfactory social and personal life. One significant outcome was the importance of proper preparation of patients for surgery and especially the need for additional postoperative psychotherapy. None of the patients regretted having had surgery. However, some were, to a degree, disappointed because of difficulties experienced postoperatively in adjusting satisfactorily as women both in their relationships with men and in living their lives generally as women. Findings of this study make a strong case for making a change in the Harry Benjamin Standards of Care to include a period of postoperative psychotherapy.

  9. Psychosocial reaction patterns to alopecia in female patients with gynecological cancer undergoing chemotherapy.

    PubMed

    Ishida, Kazuko; Ishida, Junko; Kiyoko, Kanda

    2015-01-01

    This study aims to clarify the psychosocial reactions of female patients with gynecological cancer undergoing chemotherapy and in the process of suffering from alopecia and to examine their nursing support. The target group comprised female patients who had received two or more cycles of chemotherapy, were suffering from alopecia, and were aged 30-65. Data were collected from semi-structured interviews, conducted from the time the patients were informed by their doctors that they might experience alopecia due to chemotherapy to the time they actually experienced alopecia and until they were able to accept the change. Inductive qualitative analysis was employed to close in on the subjective experiences of the cancer patients. The results showed the existence of six phases in the psychosocial reactions in the process of alopecia: phase one was the reaction after the doctor's explanation; phase two was the reaction when the hair starts to fall out; phase three was the reaction when the hair starts to intensely fall out; phase four was the reaction when the hair has completely fallen out; phase five was the reaction to behavior for coping with alopecia; and phase six was the reaction to change in interpersonal human relationships. The results also made it clear that there are five types of reaction patterns as follows: 1) treatment priority interpersonal relationship maintenance type; 2) alopecia agitated interpersonal relationship maintenance type; 3) alopecia agitated interpersonal relationship reduction type; 4) alopecia denial interpersonal relationship reduction type; and 5) alopecia denial treatment interruption type. It is important to find out which of the five types the patients belong to early during treatment and provide support so that nursing intervention that suits each individual can be practiced. The purpose of this study is to make clear the process in which patients receiving chemotherapy come to accept alopecia and to examine evidence-based nursing

  10. Atypical presentation to rocuronium allergy in a 19-year-old female patient.

    PubMed

    Kuric, Vladimir; Zaza, Khaled J; Algazlan, Sulaiman S

    2017-02-01

    The danger of anaphylaxis, a rare but life threatening complication of general anesthesia (GA) can be summarized in two: 1. General Anesthesia masks the typical early signs of allergy which can be seen in an awake patient. 2. Anaphylaxis during GA manifests mostly as circulatory/ventilatory failures which can be interpreted as adverse effects of anesthetics or surgery and this can lead to critical delay of effective therapy. A 19-year-old female admitted for posterior spinal fusion and instrumentation (the 5th surgery in patient's life) desaturated seconds after intubation. Cardiopulmonary resuscitation (CPR) was started and the absence of cutaneous signs along with a loud holosystolic murmur were questioned. The patient was promptly resuscitated and allergy to rocuronium was confirmed by intradermal tests 6weeks later. Factors influencing decision making and potential etiology of the newly heard holosystolic murmur during anaphylaxis are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Epidemiology of hospitalized female burns patients in a burn centre in Shiraz.

    PubMed

    Hosseini, R S; Askarian, M; Assadian, O

    2007-01-01

    During 2000 to 2001, all 170 female burn patients admitted to the Ghotbeddin Burn Centre in Shiraz were studied to determine the epidemiological characteristics and outcome of burn for these patients. The overall mortality rate was 64%. The highest frequency of burns (53.5%) occurred among 16-25-year-olds. The commonest cause of burn was flame (98.2%). The mean (SD) length of hospital stay was 13 (14.3) days. Mean (SD) of total body surface area (TBSA) burned among all patients was 56% (28.5%); among those who survived it was 29% (13.4%) and among those who died it was 72% (21.7%). The relation between TBSA and mortality was statistically significant.

  12. The evolution of a token economy programme for female chronic schizophrenic patients.

    PubMed

    Butler, R J

    1979-05-01

    Token economy programmes are becoming an increasingly familiar sight in British psychiatric hospitals, yet many remain inflexible and prone to breakdown after a period in operation. This paper describes the evolution of a token economy for female chronic schizophrenic patients, where the nursing staff with minimal 'psychological' support and in dealing with a programme free of research constraints, aimed to increase the therapeutic potential of the system. The major developments arose from the need: (i) to extinguish the emergence of undesirable behaviour; (2) to develop a more individualized approach to treating patients' problems; (3) to keep consistent adequate records; (4) to re-establish contact with the community and (5) to cater for patients' varied responses to treatment.

  13. Sometimes when you hear hoof beats, it could be a zebra: consider the diagnosis of Fabry disease

    PubMed Central

    2012-01-01

    Background Fabry disease is an X-linked lysosomal storage disorder that results from a deficiency of the enzyme α-galactosidase A. Fabry disease is present in 4–5% of men with unexplained left ventricular hypertrophy or cryptogenic stroke. As enzyme replacement therapy is now more widely available, it is important to recognise the signs and symptoms of the disease and establish the diagnosis so that early treatment can be started before irreversible organ damage occurs. Case Presentation A previously fit and well 32-year-old Caucasian male presented with multisystem dysfunction including renal impairment. Although he had no suggestive symptoms, a diagnosis of Fabry disease was first established on a native renal biopsy. This was confirmed by enzymatic testing and subsequent genetic analysis that revealed a potentially new pathogenic variant. Conclusions This case highlights the importance both of Fabry disease as a differential diagnosis in patients with renal impairment in the context of multi-system disease and also of adequate tissue sampling for electron microscopy when performing native renal biopsies. PMID:22849389

  14. Predictive risk factors for postoperative tetany in female patients with Graves' disease.

    PubMed

    Yamashita, H; Noguchi, S; Murakami, T; Uchino, S; Watanabe, S; Ohshima, A; Toda, M; Yamashita, H; Kawamoto, H

    2001-04-01

    Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a deficiency in calcium and vitamin D concomitant with transient hypoparathyroidism induced by surgery. In the present study, we further clarified the risk factors by referring to serum 25-hydroxyvitamin D [25(OH)D] and alkaline phosphatase. The serum levels of intact parathyroid hormone, calcium and other electrolytes, and 25-hydroxyvitamin D [25(OH)D] were measured preoperatively in 178 female patients with Graves' disease who underwent subtotal thyroidectomy. Of the 178 female patients, 15 (8.4%) developed tetany. Univariate analysis of 16 possible risk factors showed that 2 were statistically significant: serum 25(OH)D and alkaline phosphatase levels. The incidence of tetany according to the serum levels of 25(OH)D and alkaline phosphatase was 19.1% (9/47) in patients with 25(OH)D < or = 25 nmol/L and alkaline phosphatase > 155, 11.8% (4/34) in those with 25(OH)D < or = 25 nmol/L and alkaline phosphatase < or = 155, 6.7% (2/30) in those with 25(OH)D > 25 nmol/L and alkaline phosphatase > 155, and 0% (0/50) in those with 25(OH)D > 25 nmol/L and alkaline phosphatase < or = 155. Patients with Graves' disease who have vitamin D deficiency with high serum alkaline phosphatase levels are the highest-risk group for postoperative tetany. Serum 25(OH)D and alkaline phosphatase should be monitored in patients with Graves' disease.

  15. Long-Term Effects of Continuous Positive Airway Pressure Treatment on Sexuality in Female Patients with Obstructive Sleep Apnea

    PubMed Central

    Petersen, Marian; Kristensen, Ellids; Berg, Søren; Midgren, Bengt

    2013-01-01

    Introduction Results from a previous study showed that sexuality was negatively affected in females with untreated obstructive sleep apnea (OSA). Data are sparse on the long-term effects of nocturnal continuous positive airway pressure (CPAP) treatment on sexual difficulties and sexual distress in female patients with OSA. Aim The aim of the present study was to investigate the effects after 1 year of CPAP treatment on sexual difficulties, sexual distress, and manifest sexual dysfunction in female patients with OSA. The effect of CPAP on life satisfaction was also investigated. Methods Fifty-four therapy-compliant, female patients (age 22–71) received a survey before and after 1 year of nocturnal CPAP treatment. The questions on this survey were drawn from three self-administered questionnaires: two on sexuality and one on life satisfaction. The results were compared with a population sample. The Epworth Sleepiness Scale was used for assessment of daytime sleepiness. Main Outcome Measures The Female Sexual Function Index, Female Sexual Distress Scale, Manifest Female Sexual Dysfunction, four questions from Life Satisfaction 11, and the Epworth Sleepiness Scale were all used to measure outcome. Results In total, 44 patients responded to the survey (81% response rate). The results were a significant, positive change in manifest female sexual dysfunction, but no significant changes in isolated sexual difficulties or sexual distress. Daytime sleepiness significantly decreased after 1 year. The results from the Life Satisfaction 11 questionnaire remained unchanged after 1 year. Conclusions After 1 year of CPAP treatment, female patients with OSA reported reduced manifest sexual dysfunction. However, it cannot be concluded if this result is due to CPAP treatment alone. Furthermore, reduced daytime tiredness was found in the surveyed population. CPAP treatment, per se, does not seem to affect partner relationships. Petersen M, Kristensen E, Berg S, and Midgren B. Long

  16. Identification of a Novel GLA Gene Mutation, p.Ile239Met, in Fabry Disease With a Predominant Cardiac Phenotype.

    PubMed

    Csányi, Beáta; Hategan, Lidia; Nagy, Viktória; Obál, Izabella; Varga, Edina T; Borbás, János; Tringer, Annamária; Eichler, Sabrina; Forster, Tamás; Rolfs, Arndt; Sepp, Róbert

    2017-05-31

    Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutations in the GLA gene, encoding for the enzyme α-galactosidase A. Although hundreds of mutations in the GLA gene have been described, many of them are variants of unknown significance. Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. A 69 year-old female index patient with a clinical history of renal failure, hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in the GLA gene. Genetic screening identified a previously unreported heterozygous mutation in exon 5 of the GLA gene (c.717A>G; p.Ile239Met). Family screening indicated that altogether 6 family members carried the mutation (5 females, 1 male, average age: 55 ± 16 years). Three family members, including the index patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while two other family members were diagnosed with left ventricular hypertrophy. Taking affection status as the presence of hypertrophic cardiomyopathy, left ventricular hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the mutation. Linkage analysis of the family gave a two-point LOD score of 2.01 between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit of normal +2STD: ≤ 1.8 ng/mL). The GLA enzyme level was markedly reduced in the affected male family member (< 0.2 µmol/L/hour; upper limit of normal ± 2STD: ≥ 2.6 µmol/L/hour). We conclude that the p. Ile239Met GLA mutation is a pathogenic mutation for FD associated with predominant cardiac phenotype.

  17. Relation of the rs9939609 gene variant in FTO with metabolic syndrome in obese female patients.

    PubMed

    de Luis, Daniel Antonio; Aller, Rocío; Conde, Rosa; Izaola, Olatz; de la Fuente, Beatriz; Sagrado, Manuel Gonzalez

    2013-01-01

    Common polymorphisms of the fat mass and obesity associated gene (FTO) have been linked to obesity and diabetes mellitus type 2 in some populations. The aim of our study was to analyze the relationship of the rs9939609 FTO gene polymorphism with metabolic syndrome and its components. A population of 457 obese Caucasian females was analyzed in a cross-sectional survey. To estimate the prevalence of Metabolic Syndrome, the definitions of the ATPIII were considered. Genotype of FTO gene polymorphism (rs9939609) was studied. One hundred and thirty patients (28.4%) had the genotype TT (wild group), whereas 227 patients (49.7%) had the genotype TA and 100 patients (21.9%) had the genotype AA. Prevalence of metabolic syndrome (MS) with ATP III definition was 40.7% (186 patients) and 59.3% patients had no MS (n = 271). Prevalence of mutant FTO genotypes was similar in patients with metabolic syndrome (27.4% wild genotype and 72.6% mutant genotype) and without metabolic syndrome (29.2% wild genotype and 70.8% mutant genotype).Odds ratio of metabolic syndrome in wild vs mutant genotype was 1.04 (95% CI: 0.87-1.22). Insulin levels (13.9±6.3 mUI/L vs. 12.6 ± 3.4 mUI/L; p<0.05), HOMA-R (3.3 ± 1.6 vs. 2.8 ± 1.4; p < 0.05) and triglycerides concentrations (110.8 ± 27.3 mg/dl vs. 103.1 ± 47.3 mg/dl; p < 0.05) were lower in the mutant type group than the wild type group in patients without metabolic syndrome. The FTO gene polymorphism (rs9939609) was found to be associated with increased insulin resistance, insulin and triglyceride levels in obese females with TT variant and without metabolic syndrome. MS or its components were not associated with this polymorphism in obese females. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Hypercalcemia in a male-to-female transgender patient after body contouring injections: a case report

    PubMed Central

    2014-01-01

    Introduction Body contouring injections by non-licensed providers are frequently sought out by a subset of the male-to-female transgender community. Although short-term side effects such as pulmonary embolism and injection site infection are well known, long-term consequences of such practices are less well studied. Case presentation Here we describe the case of a 40-year-old African American male-to-female transgender patient who presented to our institution with hypercalcemia and acute renal failure secondary to body contouring injections with industrial strength silicone by non-licensed providers, a decade prior to her visit. Work-up revealed an extensive granulomatous inflammatory process in the injection area resulting in electrolyte abnormalities and kidney injury. The patient’s lab results and symptoms responded well to long-term corticosteroid treatment and correlated with treatment adherence. Conclusion Affected patients can sometimes present with unusual clinical symptoms many years after silicone injections. In a constantly growing transgender community that often utilizes non-licensed providers for silicone injections, the medical community will likely face an increasing number of patients with long-term side effects of such practices. Therefore, it is imperative for physicians to recognize such cases promptly and initiate potentially life-saving treatment. PMID:24572248

  19. Relationship between biological factors and catastrophizing and clinical outcomes for female patients with knee osteoarthritis.

    PubMed

    Ikemoto, Tatsunori; Miyagawa, Hirofumi; Shiro, Yukiko; Arai, Young-Chang Park; Akao, Machiko; Murotani, Kenta; Ushida, Takahiro; Deie, Masataka

    2017-03-18

    To investigate the correlations between clinical outcomes and biopsychological variables in female patients with knee osteoarthritis (OA). Seventy-seven patients with symptomatic knee OA were enrolled in this study. We investigated the age, body mass index (BMI), pain catastrophizing scale (PCS) and radiographic severity of bilateral knees using a Kellgren-Lawrence (K-L) grading system of the subjects. Subsequently, a multiple linear regression was conducted to determine which variables best correlated with main outcomes of knee OA, which were pain severity, moving capacity by measuring timed-up-and-go test and Japanese Knee Osteoarthritis Measure (JKOM). We found that the significant contributor to pain severity was PCS (β = 0.555) and BMI (β = 0.239), to moving capacity was K-L grade (β = 0.520) and to PCS (β = 0.313), and to a JKOM score was PCS (β = 0.485) and K-L grade (β = 0.421), respectively. The results suggest that pain catastrophizing as well as biological factors were associated with clinical outcomes in female patients with knee OA, irrespective of radiographic severity.

  20. Relationship between biological factors and catastrophizing and clinical outcomes for female patients with knee osteoarthritis

    PubMed Central

    Ikemoto, Tatsunori; Miyagawa, Hirofumi; Shiro, Yukiko; Arai, Young-Chang Park; Akao, Machiko; Murotani, Kenta; Ushida, Takahiro; Deie, Masataka

    2017-01-01

    AIM To investigate the correlations between clinical outcomes and biopsychological variables in female patients with knee osteoarthritis (OA). METHODS Seventy-seven patients with symptomatic knee OA were enrolled in this study. We investigated the age, body mass index (BMI), pain catastrophizing scale (PCS) and radiographic severity of bilateral knees using a Kellgren-Lawrence (K-L) grading system of the subjects. Subsequently, a multiple linear regression was conducted to determine which variables best correlated with main outcomes of knee OA, which were pain severity, moving capacity by measuring timed-up-and-go test and Japanese Knee Osteoarthritis Measure (JKOM). RESULTS We found that the significant contributor to pain severity was PCS (β = 0.555) and BMI (β = 0.239), to moving capacity was K-L grade (β = 0.520) and to PCS (β = 0.313), and to a JKOM score was PCS (β = 0.485) and K-L grade (β = 0.421), respectively. CONCLUSION The results suggest that pain catastrophizing as well as biological factors were associated with clinical outcomes in female patients with knee OA, irrespective of radiographic severity. PMID:28361021

  1. Impact of Radiotherapy on Fertility, Pregnancy, and Neonatal Outcomes in Female Cancer Patients

    SciTech Connect

    Wo, Jennifer Y.; Viswanathan, Akila N.

    2009-04-01

    Purpose: Radiation has many potential long-term effects on cancer survivors. Female cancer patients may experience decreased fertility depending on the site irradiated. Oncologists should be aware of these consequences and discuss options for fertility preservation before initiating therapy. Methods and Materials: A comprehensive review of the existing literature was conducted. Studies reporting the outcomes for female patients treated with cranio-spinal, abdominal, or pelvic radiation reporting fertility, pregnancy, or neonatal-related outcomes were reviewed. Results: Cranio-spinal irradiation elicited significant hormonal changes in women that affected their ability to become pregnant later in life. Women treated with abdomino-pelvic radiation have an increased rate of uterine dysfunction leading to miscarriage, preterm labor, low birth weight, and placental abnormalities. Early menopause results from low-dose ovarian radiation. Ovarian transposition may decrease the rates of ovarian dysfunction. Conclusions: There is a dose-dependent relationship between ovarian radiation therapy (RT) and premature menopause. Patients treated with RT must be aware of the impact of treatment on fertility and explore appropriate options.

  2. Accuracy of an intimate partner violence screening tool for female VHA patients: a replication and extension.

    PubMed

    Iverson, Katherine M; King, Matthew W; Gerber, Megan R; Resick, Patricia A; Kimerling, Rachel; Street, Amy E; Vogt, Dawne

    2015-02-01

    The 4-item Hurt/Insult/Threaten/Scream (HITS) tool accurately detects past-year intimate partner violence (IPV) among female Veterans Health Administration (VHA) patients; however, it lacks a sexual IPV item. This study evaluated the accuracy of an extended HITS (E-HITS), which adds a sexual IPV item, in female VHA patients. A sample of 80 female U.S. veteran VHA patients in New England completed a mail survey (50.0% response rate) that included the 5-item E-HITS and the Revised Conflict Tactics Scales (CTS-2). Women were included if they were in an intimate relationship in the past year. The women averaged 49 years of age and 86.0% of the sample was White. Accuracy of the 4-item HITS was compared to the 5-item E-HITS, using the CTS-2 as the reference. There were 20 women (25.0%) who reported past-year IPV on the CTS-2. The receiver operator characteristic curves demonstrated that the HITS and E-HITS performed nearly identically at their optimal cutoff scores of 6 and 7, respectively. At these cutoff scores, the sensitivity of both tools was .75, 95% CI [.55, .95]. The specificities were similar; .83 for the HITS, 95% CI [.73, .92], and .82 for the E-HITS, 95% CI [.72, .90]. Including a sexual IPV item may be clinically beneficial; it also attains the same accuracy of case identification as the HITS. Published 2015. This article is a US government work and is in the public domain in the USA.

  3. Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

    PubMed Central

    Semlali, Abdelhabib; Parine, Narasimha Reddy; Al Amri, Abdullah; Azzi, Arezki; Arafah, Maha; Kohailan, Muhammad; Shaik, Jilani P; Almadi, Majid Abdulrahman; Aljebreen, Abdulrahman M; Alharbi, Othman; Ali Azzam, Nahla; Rouabhia, Mahmoud; Alanazi, Mohammad Saud

    2017-01-01

    Objective The authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population. Methods In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene’s promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues. Results The authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area. Conclusion The findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females with rectal cancer. PMID:28031717

  4. A novel 6 bp insertion in exon 7 associated with an unusual phenotype in a family with Fabry disease.

    PubMed

    Kroepfl, Th; Paul, K; Kotanko, P; Plecko, B; Paschke, E

    2002-12-01

    A male patient presented with oligosymptomatic Fabry disease (end stage renal failure and non-obstructive cardiomyopathy) at around 30 years of age. His leukocyte alpha-galactosidase activity (alpha-gal) was 2.6% of controls. A 50-year-old sister had similar cardiac symptoms and her asymptomatic heterozygous daughter (33 years) had normal enzyme activity. All three patients carried a novel, 6bp insertion on exon 7 of the AGAL gene. The majority of male Fabry patients carrying mutations in exon 7 have residual alpha-gal below 1% and suffer from neuropathic pain. Comparable oligosymptomatic phenotypes in Caucasian patients carry a common mutation on exon 6 (R301Q) and have a significantly later onset. The course of the disease is likely to be altered by recombinant enzyme therapy in the future. Therefore, a thorough documentation of phenotypes, residual activities and underlying genotypes is of current interest.

  5. Variables related to behavioral and emotional problems and gender typed behaviors in female patients with congenital adrenal hyperplasia.

    PubMed

    Oner, Ozgur; Aycan, Zehra; Tiryaki, Tugrul; Soy, Derya; Cetinkaya, Ergun; Kibar, Esin

    2009-02-01

    We investigated the effects of type of congenital adrenal hyperplasia (CAH), treatment, endocrinological, surgical, and socio-demographic factors as well as patients' body perception on the gender-typed play and behavioral and emotional problems in female children with CAH. The sample included 28 females with CAH (mean age: 12.6 years). We compared patients with CAH to 28 age-matched patients with type 1 diabetes mellitus and 28 healthy controls. Patients with CAH had significantly higher externalization and total problems scores and were less interested in typically female behaviors. The behavioral and emotional problems in patients with CAH were associated with patient satisfaction with the appearance of their genitalia, the surgeons' assessment of the success of the surgical procedures, and mean testosterone level. Our results showed the severity of the behavioral and emotional problems was associated with severity of androgenization, patients' perception of their genitalia and the surgical outcome.

  6. Primary mucinous adenocarcinoma of the larynx in female patient: a rare entity.

    PubMed

    Ebru, Tastekin; Omer, Yalcin; Fulya, Oz Puyan; Ufuk, Usta; Kemal, Kutlu

    2012-10-01

    Laryngeal malignant tumors are mainly composed of squamous cell carcinomas. Glandular carcinomas of the larynx are rare tumors that constitute less than 1% of all laryngeal malignancies where "adenocarcinoma not otherwise specified" is the most common histologic subtype. Here we report a case of a 70-year-old female patient with primary laryngeal mucinous adenocarcinoma. The rarity of the tumor type and the differential diagnosis of this tumor before reporting it as a primary adenocarcinoma of the larynx are discussed here with literature findings.

  7. Cemento-ossifying fibroma of maxillary antrum in a young female patient.

    PubMed

    Singhal, A; Ram, R; Singhal, P; Bhatnagar, S; Das, U M

    2011-12-01

    The cemento-ossifying fibroma is classified as a fibro-osseous lesion of the jaws. It commonly presents as a progressively growing lesion that can attain an enormous size with resultant deformity if left untreated. The cemento-ossifying fibroma is a central neoplasm of bone as well as periodontium which has caused considerable controversy because of controversy regarding terminology and the criteria for its diagnosis. This case report describes a female patient with cemento-ossifying fibroma involving maxillary antrum. The clinical, radiographic and histological features as well as the surgical findings are presented.

  8. [Multiple gangrene of the digits in a female patient with liver cirrhosis, diabetes mellitus and cryoglobulinemia].

    PubMed

    Lazarov, G; Tsanev, A

    1985-01-01

    A case is described with multiple gangrene of the fingers of a female, aged 55, with confirmed cirrhosis of liver and diabetes mellitus. Cryoglobulins were established in the serum. A disturbed immunological balance was present and the family loading with collagenosis raises the problem of genetic moments of the disturbed homeostasis. The existing diabetic microangiopathy, histologically confirmed by biopsy of skin and subcutaneous tissue, brings forward the question of the complex pathogenesis of gangrene. At the end of her stay in the clinic, the patient developed cerebral apoplexy.

  9. A young female patient of neuromyelitis optica presenting with hypocalcemic tetany.

    PubMed

    Tirkey, Naveen Kumar; Mandavi, Sanjay; Gupta, Shashank

    2011-09-01

    Neuromyelitis optica, a variant of multiple sclerosis, presenting with hypocalcemic tetany is an unusual presentation. We report here a case of 25 years old female who was a case of neuromyelitis optica and had hypocalcemic tetany as the initial presentation among others. The case is interesting in that the hypocalcemic tetany was not coincidental. The patient had low vitamin D status and probably, this was correlated etiologically to neuromyelitis optica. Vitamin D has immunomodulatory effect and low vitamin D status has been implicated in the etiology of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease.

  10. An elderly female patient with tardive oromandibular dystonia after prolonged use of the histamine analog betahistine.

    PubMed

    De Riu, G; Sanna, M P; De Riu, P L

    2010-10-01

    Tardive oromandibular dystonia (OMD) is iatrogenic in origin and is characterised by orofacial and lingual stereotypes more frequently than the idiopathic form of OMD Tardive OMD is often associated with anti-dopaminergic treatment involving drugs such as anti-psychotics, anti-emetics, and anti-vertigo agents, although the syndrome can also be triggered by anti-epileptic or anti-depressant drugs that do not have anti-dopaminergic properties. We report an elderly female patient with OMD after prolonged, self-administered treatment with betahistine dihydrochloride, a histamine analogue.

  11. Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications

    PubMed Central

    Weidemann, F; Niemann, M; Störk, S; Breunig, F; Beer, M; Sommer, C; Herrmann, S; Ertl, G; Wanner, C

    2013-01-01

    Objective The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards ‘hard’ clinical end-points in comparison with the natural course of the disease. Methods A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain. Results During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min−1 per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry. Conclusion Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease. PMID:23586858