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Sample records for adult onset disease

  1. [Adult-onset rare diseases].

    PubMed

    Pfliegler, György; Kovács, Erzsébet; Kovács, György; Urbán, Krisztián; Nagy, Valéria; Brúgós, Boglárka

    2014-03-02

    The present paper is focusing on rare diseases manifesting in late childhood or adulthood. A part of these syndromes are not of genetic origin, such as relatively or absolutely rare infections, autoimmune diseases, tumours, or diseases due to rare environmental toxic agents. In addition, even a large proportion of genetic disorders may develop in adulthood or may have adult forms as well, affecting are almost each medical specialization. Examples are storage disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation, antithrombin deficiency), or some rare monogenic disorders such as Huntington-chorea and many others. It is now generally accepted that at least half of the 6-8000 "rare diseases" belong either to the scope of adult-care (e.g. internal medicine, neurology), or to "age-neutral" specialities such as ophtalmology, dermatology etc.).

  2. Refractory Coats’ Disease of Adult Onset

    PubMed Central

    Beselga, D.; Campos, A.; Mendes, S.; Carvalheira, F.; Castro, M.; Castanheira, D.

    2012-01-01

    Purpose We present the case of an 18-year-old Caucasian male with a unilateral macular star and retinal vascular anomalies compatible with adult onset Coats’ disease. Methods Diagnosis was based on fundoscopic, fluorescein angiography and optical coherence tomography findings. Results The patient presented to our emergency department with complaints of low vision in his left eye (LE) detected 10 days before. The best-corrected visual acuity in the LE was 20/50. Fundoscopy of the LE evidenced a complete macular star. Optical coherence tomography showed increased retinal thickness, infiltration of the retinal wall, and detachment of the neuroepithelium. Angiography revealed no appreciable diffusion in the macula. Above the superior temporal (ST) arcade, anomalies in the retinal vasculature were found, with interruption of the peripheral vessels and vessels which were ‘sausage’-like. After 1 month, the LE vision evolved to hand movements. Laser photocoagulation was performed in the ST quadrant. Intravitreal injection of bevacizumab 1.25 mg/0.05 ml and photodynamic therapy were performed without any significant changes, progression of ST serous detachment of the neuroepithelium, and finally progression to macular fibrosis. Discussion Coats’ disease is usually diagnosed in childhood, but rare cases may occur in adults. Those cases usually have a more indolent course which was not observed in our patient. When there is macular involvement, prognosis is more guarded, despite treatment. PMID:22548045

  3. Adult Onset Still's Disease and Rocky Mountain Spotted Fever.

    PubMed

    Persad, Paul; Patel, Rajendrakumar; Patel, Niki

    2010-01-01

    Adult Still's Disease was first described in 1971 by Bywaters in fourteen adult female patients who presented with symptoms indistinguishable from that of classic childhood Still's Disease (Bywaters, 1971). George Still in 1896 first recognized this triad of quotidian (daily) fevers, evanescent rash, and arthritis in children with what later became known as juvenile inflammatory arthritis (Still, 1990). Adult Onset Still's Disease (AOSD) is an inflammatory condition of unknown etiology characterized by an evanescent rash, quotidian fevers, and arthralgias. Numerous infectious agents have been associated with its presentation. This case is to our knowledge the first presentation of AOSD in the setting of Rocky Mountain Spotted Fever. Although numerous infectious agents have been suggested, the etiology of this disorder remains elusive. Nevertheless, infection may in fact play a role in triggering the onset of symptoms in those with this disorder. Our case presentation is, to our knowledge, the first case of Adult Onset Still's Disease associated with Rocky Mountain spotted fever (RMSF).

  4. Hepatitis A infection mimicking adult onset Still's disease.

    PubMed

    Sridharan, S; Mossad, S; Hoffman, G

    2000-07-01

    Fever, rash, and arthritis may be components of the prodrome of viral hepatitis. In the absence of jaundice and abnormal liver function tests, this form of polyarthritis is easily confused with primary autoimmune diseases. Whereas the association of systemic illness with musculoskeletal symptoms and numerous viral infections is well known, such an association with hepatitis A has only been rarely reported. We describe a case of hepatitis A infection mimicking adult onset Still's disease, and review the pathogenesis and differential diagnosis of Still's disease and the extraarticular manifestations of hepatitis.

  5. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease

    PubMed Central

    Sone, Jun; Mori, Keiko; Inagaki, Tomonori; Katsumata, Ryu; Takagi, Shinnosuke; Yokoi, Satoshi; Araki, Kunihiko; Kato, Toshiyasu; Nakamura, Tomohiko; Koike, Haruki; Takashima, Hiroshi; Hashiguchi, Akihiro; Kohno, Yutaka; Kurashige, Takashi; Kuriyama, Masaru; Takiyama, Yoshihisa; Tsuchiya, Mai; Kitagawa, Naoyuki; Kawamoto, Michi; Yoshimura, Hajime; Suto, Yutaka; Nakayasu, Hiroyuki; Uehara, Naoko; Sugiyama, Hiroshi; Takahashi, Makoto; Kokubun, Norito; Konno, Takuya; Katsuno, Masahisa; Tanaka, Fumiaki; Iwasaki, Yasushi; Yoshida, Mari

    2016-01-01

    Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated ‘dementia dominant group’, followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated ‘limb weakness group’, followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and

  6. [Kimura's disease: an unrecognized cause of adult-onset nephrotic syndrome with minimal change disease].

    PubMed

    Shehwaro, N; Langlois, A-L; Gueutin, V; Debchi, L; Charlotte, F; Rouvier, P; Rottembourg, J; Izzedine, H

    2014-02-01

    Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

  7. Refractory Genital HPV Infection and Adult-Onset Still Disease

    PubMed Central

    Yu, Xin; Zheng, Heyi

    2016-01-01

    Abstract Adult-onset Still disease (AOSD) is a systemic autoimmune disease (AIID) that can develop after exposure to infectious agents. Genital human papillomavirus (HPV) infection has been reported to induce or exacerbate AIIDs, such as systemic lupus erythematosus (SLE). No guidelines are available for the management of genital warts in AOSD. Case report and literature review. We report a patient who was diagnosed AOSD in the setting of refractory and recurrent genital HPV infection, demonstrating a possible link between HPV infection and AOSD. In addition, we also discuss the management of genital warts in patients with AOSD. To the best of our knowledge, no previous cases of AOSD with genital HPV infection have been reported in literature. We then conclude that the patient AOSD may be triggered by primary HPV infection. Larger number of patient samples is needed to confirm whether HPV could trigger AOSD. PMID:27082556

  8. Efficacy of Anakinra in Refractory Adult-Onset Still's Disease

    PubMed Central

    Ortiz-Sanjuán, Francisco; Blanco, Ricardo; Riancho-Zarrabeitia, Leyre; Castañeda, Santos; Olivé, Alejandro; Riveros, Anne; Velloso-Feijoo, María.L.; Narváez, Javier; Jiménez-Moleón, Inmaculada; Maiz-Alonso, Olga; Ordóñez, Carmen; Bernal, José A.; Hernández, María V.; Sifuentes-Giraldo, Walter A.; Gómez-Arango, Catalina; Galíndez-Agirregoikoa, Eva; Blanco-Madrigal, Juan; Ortiz-Santamaria, Vera; del Blanco-Barnusell, Jordi; De Dios, Juan R.; Moreno, Mireia; Fiter, Jordi; Riscos, Marina de los; Carreira, Patricia; Rodriguez-Valls, María J.; González-Vela, M. Carmen; Calvo-Río, Vanesa; Loricera, Javier; Palmou-Fontana, Natalia; Pina, Trinitario; Llorca, Javier; González-Gay, Miguel A.

    2015-01-01

    Abstract Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2–6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3–47.5] mg/day at ANK onset to 5 [0–10] at 12 months. After a median [IQR] follow-up of 16 [5–50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations. PMID:26426623

  9. Parenchymal lung involvement in adult-onset Still disease

    PubMed Central

    Gerfaud-Valentin, Mathieu; Cottin, Vincent; Jamilloux, Yvan; Hot, Arnaud; Gaillard-Coadon, Agathe; Durieu, Isabelle; Broussolle, Christiane; Iwaz, Jean; Sève, Pascal

    2016-01-01

    Abstract Parenchymal lung involvement (PLI) in adult-onset Still's disease (AOSD) has seldom, if ever, been studied. We examine here retrospective cohort AOSD cases and present a review of the literature (1971–2014) on AOSD-related PLI cases. Patients with PLI were identified in 57 AOSD cases. For inclusion, the patients had to fulfill Yamaguchi or Fautrel classification criteria, show respiratory symptoms, and have imaging evidence of pulmonary involvement, and data allowing exclusion of infectious, cardiogenic, toxic, or iatrogenic cause of PLI should be available. This AOSD + PLI group was compared with a control group (non–PLI-complicated AOSD cases from the same cohort). AOSD + PLI was found in 3 out of the 57 patients with AOSD (5.3%) and the literature mentioned 27 patients. Among these 30 AOSD + PLI cases, 12 presented an acute respiratory distress syndrome (ARDS) and the remaining 18 another PLI. In the latter, a nonspecific interstitial pneumonia computed tomography pattern prevailed in the lower lobes, pulmonary function tests showed a restrictive lung function, the alveolar differential cell count was neutrophilic in half of the cases, and the histological findings were consistent with bronchiolitis and nonspecific interstitial pneumonia. Corticosteroids were fully efficient in all but 3 patients. Ten out of 12 ARDS cases occurred during the first year of the disease course. All ARDS-complicated AOSD cases received corticosteroids with favorable outcomes in 10 (2 deceased). Most PLIs occurred during the systemic onset of AOSD. PLI may occur in 5% of AOSDs, of which ARDS is the most severe. Very often, corticosteroids are efficient in controlling this complication. PMID:27472698

  10. Adult onset Still’s disease with dermatopathic lymphadenopathy

    PubMed Central

    Qureshi, Ahmad Z.; AlSheef, Mohammad; Qureshi, Waqas T.; Amjad, Waseem

    2016-01-01

    Adult onset Still’s disease (AOSD) is a chronic inflammatory disorder involving multiple systems. The symptoms mimic those of lymphomas, therefore, the diagnosis of lymphoma needs to be excluded prior to establishing the diagnosis of AOSD. Another similar condition is dermatopathic lymphadenopathy (DL). In DL, the histopathological appearance of lymph node biopsy may also mimic AOSD. The DL is associated with several systemic pathologies, such as malignant lymphomas, and rarely AOSD. We present a case of a 43-year-old male presented with 3 months history of fatigue, fever, and lymphadenopathy. Initial work-up satisfactorily met the criteria for diagnosis of AOSD. But considering the well-known association of DL with hematological malignancies, detailed pathological studies were considered, including tumor markers to rule out the possibility of malignancy. The patient was started on steroids and showed remarkable recovery within 2 weeks. Evaluation of malignant lymphomas in a patient with DL is important, in order to diagnose AOSD and rule out hematological malignancy. PMID:27761568

  11. Adult-onset Still's disease with atypical cutaneous manifestations

    PubMed Central

    Narváez Garcia, Francisco Javier; Pascual, María; López de Recalde, Mercè; Juarez, Pablo; Morales-Ivorra, Isabel; Notario, Jaime; Jucglà, Anna; Nolla, Joan M.

    2017-01-01

    Abstract The diagnosis of adult-onset Still's disease (AOSD) can be very difficult. There are no specific tests available, and diagnosis is usually based on a symptom complex and the well-described typical evanescent rash seen in the majority of patients. However, in recent years, other atypical cutaneous manifestations of AOSD have been reported. These atypical skin eruptions often present in addition to the typical evanescent rash but may also be the only skin manifestation, resulting in delayed diagnosis because of under-recognition. In this study, we present 3 new cases of AOSD with atypical cutaneous manifestations diagnosed during a 30-year period in our department and review 78 additional cases previously reported (PubMed 1990–2016). These 81 patients form the basis of the present analysis. The overall prevalence of atypical cutaneous manifestations in our AOSD population was 14%. These manifestations may appear at any time over the course of the disease, and usually occur in patients who have persistent and severe disease, with a considerable frequency of clinical complications (23%), including serositis, myopericarditis, lung involvement, abdominal pain, neurologic involvement, and reactive hemophagocytic syndrome. The most representative and frequent lesion among the nonclassical skin rashes is the development of persistent pruritic papules and/or plaques. Interestingly, these lesions show a distinctive histological pattern. Other, less frequently observed lesions include urticaria and urticaria-like eruptions, generalized or widespread non-pruritic persistent erythema, vesiculopustular eruptions, a widespread peau d’orange appearance of the skin, and edema of the eyelids mimicking dermatomyositis without any accompanying skin lesion. The great majority of these patients required medium or high doses of glucocorticoids (including intravenous methylprednisolone pulse therapy in some cases) and, in nearly 40%, a more potent or maintenance immunotherapy

  12. Adult-Onset Esophageal Crohn’s Disease

    PubMed Central

    Kasarala, George; Durrett, Sam

    2016-01-01

    Crohn’s disease (CD) is an idiopathic inflammatory bowel disease that can involve any part of the gastrointestinal tract. Esophageal involvement is rarely seen in adults, especially at the initial diagnosis of CD. Esophageal symptoms as primary manifestations of the disease are extremely rare. We report a case of a CD with esophageal involvement at the time of her initial diagnosis of CD. PMID:27761477

  13. Adult onset Hallervorden-Spatz disease with psychotic symptoms.

    PubMed

    del Valle-López, Pilar; Pérez-García, Rosa; Sanguino-Andrés, Rosa; González-Pablos, Emilio

    2011-01-01

    Hallervorden-Spatz disease is a rare neurological disorder characterized by pyramidal and extrapyramidal manifestations, dysarthria and dementia. Its onset is usually in childhood and most patients have a fatal outcome in few years. A high percentage of cases are hereditary with a recessive autosomal pattern. In the majority of the patients reported, a mutation of the gene that encodes the pantothenate kinase (PANK2) located in the 20p13-p12.3 chromosome that causes iron storage in the basal ganglia of the brain has been found. Its diagnosis is based on clinical symptoms as well as specific MRI imaging findings. The most common psychiatric features are cognitive impairment as well as depressive symptoms. There are few documented cases with psychotic disorders. We present the case of a patient with late onset Hallervorden-Spatz disease and psychotic symptoms that preceded the development of neurological manifestations. The pathophysiology and the treatment of psychotic symptomatology are presented and discussed. Key words: Psicosis, Hallervorden-Spatz, late onset, Basal ganglia.

  14. Sandhoff disease mimicking adult-onset bulbospinal neuronopathy.

    PubMed Central

    Thomas, P K; Young, E; King, R H

    1989-01-01

    A 32 year old male is described with an onset of upper limb postural tremor in adolescence followed by muscle cramps. Progressive proximal amyotrophy and weakness in the limbs developed late in the third decade. Examination disclosed, in addition, bilateral facial weakness and mild dysarthria. Enzyme studies revealed hexosaminidase A and B deficiency, indicating a diagnosis of Sandhoff disease. Intra-axonal membranocytoplasmic bodies were present in a rectal biopsy. The presentation, which resembled that of X-linked bulbospinal neuronopathy, widens the clinical spectrum for disorders related to G(M2) gangliosidosis. Images PMID:2795083

  15. Adult-onset Still's disease and cardiac tamponade: a rare association.

    PubMed

    Carrilho-Ferreira, Pedro; Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-06-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity.

  16. Adult-Onset Still's Disease and Cardiac Tamponade: A Rare Association

    PubMed Central

    Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-01-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity. PMID:26175648

  17. Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

    PubMed

    Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

    2014-04-01

    Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients.

  18. [Adult onset Still's disease as a diagnostics challenge in case of fever of unknown origin].

    PubMed

    Debski, Marcin; Stepniewski, Piotr; Wróbel, Michał

    2013-01-01

    Fever of unknown origin is often a diagnostic challenge. Here we present a case of 55-year-old woman with a history of a few months fever, progressing weakness and salmon-coloured, macular skin rash. The differential diagnosis included neoplasmatic conditions, infections and connective tissue disorders. Finally adult onset Still's disease was suspected. Glucocorticosteroid treatment was induced. During the therapy a central nervous system infection occurred, which was fatal for the patient. The presented clinical case shows that among many causes of fever of unknown origin, adult onset Still's disease should be taken into account.

  19. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

    PubMed

    Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

    2012-12-01

    The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease.

  20. Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2012-01-01

    Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

  1. Epidemiology and outcome of articular complications in adult onset Still's disease.

    PubMed

    Mahfoudhi, Madiha; Shimi, Rafik; Turki, Sami; Kheder, Adel

    2015-01-01

    The adult onset Still's disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 18 cases of adult onset Still disease diagnosed from 1990 to 2014 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 11 women and 7 men. The average age was 27 years. The arthralgias were reported in all cases; while, the arthritis interested thirteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The Standard articular radiographs were normal in ten cases. The treatment associated essentially non-steroidal anti-inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 40% and the chronic articular form in 35% of our patients. The adult onset Still's disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes.

  2. Adult-onset Still's disease as a mask of Hodgkin lymphoma

    PubMed Central

    Pawlak-Buś, Katarzyna; Leszczyński, Piotr

    2015-01-01

    Adult-onset Still's disease is a rare disorder, which creates difficulties in making a proper diagnosis. Ambiguous symptoms and results of auxiliary tests, lack of unequivocal diagnostic tests and the need to exclude other causes of the disease are major problems in clinical practice. A case of a 22-year-old woman with dominated recurrent fever, significantly elevated inflammation markers and arthritis is presented. Based on clinical signs after exclusion of infection, hematological and other reasons, the patient was diagnosed with adult-onset Still's disease. Standard treatment, with high doses of glucocorticoids and a disease-modifying drug, was applied, without the anticipated effects. The diagnostic tests were conducted again due to the lack of clinical improvement, increase of inflammatory markers and unusual response to treatment. A new symptom of significance, i.e. mediastinal lymphadenopathy, was found. After the histopathological examination of lymph nodes, Hodgkin's disease was diagnosed and targeted therapy for hematological malignancy was applied. PMID:27407236

  3. Adult-onset Still's disease as a mask of Hodgkin lymphoma.

    PubMed

    Dudziec, Ewa; Pawlak-Buś, Katarzyna; Leszczyński, Piotr

    2015-01-01

    Adult-onset Still's disease is a rare disorder, which creates difficulties in making a proper diagnosis. Ambiguous symptoms and results of auxiliary tests, lack of unequivocal diagnostic tests and the need to exclude other causes of the disease are major problems in clinical practice. A case of a 22-year-old woman with dominated recurrent fever, significantly elevated inflammation markers and arthritis is presented. Based on clinical signs after exclusion of infection, hematological and other reasons, the patient was diagnosed with adult-onset Still's disease. Standard treatment, with high doses of glucocorticoids and a disease-modifying drug, was applied, without the anticipated effects. The diagnostic tests were conducted again due to the lack of clinical improvement, increase of inflammatory markers and unusual response to treatment. A new symptom of significance, i.e. mediastinal lymphadenopathy, was found. After the histopathological examination of lymph nodes, Hodgkin's disease was diagnosed and targeted therapy for hematological malignancy was applied.

  4. Adult-Onset Asthma to Coronary Heart Disease and Stroke

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Asthma has been associated with atherosclerotic disease in several studies with some evidence that this association may be limited to women. However, most previous studies have failed to account for the heterogeneity of asthma subtypes. We previously reported increased carotid intima medial thickne...

  5. [Adult-onset Still's disease with liver failure requiring liver transplantation].

    PubMed

    Terán, Alvaro; Casafont, Fernando; Fábrega, Emilio; Martínez-Taboada, Víctor Manuel; Rodríguez-Valverde, Vicente; Pons-Romero, Fernando

    2009-12-01

    We present the case of a 23-year-old man with fever of unknown origin, who developed acute liver failure 2 months after symptom onset, requiring an urgent liver transplantation. The diagnosis of adult-onset Still's disease was established after the reappearance of symptoms after transplantation, and high doses of corticosteroids were used to control disease activity. Subsequently, given the impossibility of tapering the steroid dose, interleukin-1 receptor blocking treatment was started with satisfactory outcome. We also review the published literature.

  6. Childhood-Onset Disease Predicts Mortality in an Adult Cohort of Patients with Systemic Lupus Erythematosus

    PubMed Central

    Hersh, Aimee O.; Trupin, Laura; Yazdany, Jinoos; Panopalis, Peter; Julian, Laura; Katz, Patricia; Criswell, Lindsey A.; Yelin, Edward

    2013-01-01

    Objective To examine childhood-onset disease as a predictor of mortality in a cohort of adult patients with systemic lupus erythematosus (SLE). Methods Data were derived from the University of California Lupus Outcomes Study, a longitudinal cohort of 957 adult subjects with SLE that includes 98 subjects with childhood-onset SLE. Baseline and follow-up data were obtained via telephone interviews conducted between 2002-2007. The number of deaths during 5 years of follow-up was determined and standardized mortality ratios (SMRs) for the cohort, and across age groups, were calculated. Kaplan-Meier life table analysis was used to compare mortality rates between childhood (defined as SLE diagnosis <18 years) and adult-onset SLE. Multivariate Cox proportional hazard models were used to determine predictors of mortality. Results During the median follow-up period of 48 months, 72 deaths (7.5% of subjects) occurred, including 9 (12.5%) among those with childhood-onset SLE. The overall SMR was 2.5 (CI 2.0-3.2). In Kaplan-Meier survival analysis, after adjusting for age, childhood-onset subjects were at increased risk for mortality throughout the follow-up period (p<0.0001). In a multivariate model adjusting for age, disease duration and other covariates, childhood-onset SLE was independently associated with an increased mortality risk (hazard ratio [HR]: 3.1; 95% confidence interval [CI]: 1.3-7.3), as was low socioeconomic status measured by education (HR: 1.9; 95% CI 1.1-3.2) and end stage renal disease (HR: 2.1; 95% CI 1.1-4.0). Conclusion Childhood-onset SLE was a strong predictor of mortality in this cohort. Interventions are needed to prevent early mortality in this population. PMID:20235215

  7. Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline.

    PubMed

    Manikkam, Mohan; Haque, M Muksitul; Guerrero-Bosagna, Carlos; Nilsson, Eric E; Skinner, Michael K

    2014-01-01

    Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures.

  8. Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population

    PubMed Central

    Ostrowski, Jerzy; Paziewska, Agnieszka; Lazowska, Izabella; Ambrozkiewicz, Filip; Goryca, Krzysztof; Kulecka, Maria; Rawa, Tomasz; Karczmarski, Jakub; Dabrowska, Michalina; Zeber-Lubecka, Natalia; Tomecki, Roman; Kluska, Anna; Balabas, Aneta; Piatkowska, Magdalena; Paczkowska, Katarzyna; Kierkus, Jaroslaw; Socha, Piotr; Lodyga, Michal; Rydzewska, Grazyna; Klopocka, Maria; Mierzwa, Grazyna; Iwanczak, Barbara; Krzesiek, Elzbieta; Bak-Drabik, Katarzyna; Walkowiak, Jaroslaw; Klincewicz, Beata; Radwan, Piotr; Grzybowska-Chlebowczyk, Urszula; Landowski, Piotr; Jankowska, Agnieszka; Korczowski, Bartosz; Starzynska, Teresa; Albrecht, Piotr; Mikula, Michal

    2016-01-01

    Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components. PMID:28008999

  9. [Pathophysiology, subtypes, and treatments of adult-onset Still's disease: An update].

    PubMed

    Gerfaud-Valentin, M; Sève, P; Hot, A; Broussolle, C; Jamilloux, Y

    2015-05-01

    Adult-onset Still's disease is a rare and difficult to diagnose multisystemic disorder considered as a multigenic autoinflammatory syndrome. Its immunopathogenesis seems to be at the crossroads between inflammasomopathies and hemophagocytic lymphohistiocytosis, the most severe manifestation of the disease. According to recent insights in the pathophysiology and thanks to cohort studies and therapeutic trials, two phenotypes of adult-onset Still's disease may be distinguished: a systemic pattern, initially highly symptomatic and with a higher risk to exhibit life-threatening complications such as reactive hemophagocytic lymphohistiocytosis, where interleukin-1 blockade seems to be very effective, a chronic articular pattern, more indolent with arthritis in the foreground and less severe systemic manifestations, which would threat functional outcome and where interleukin-6 blockade seems to be more effective. This review focuses on these data.

  10. Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort

    PubMed Central

    Lovasz, Barbara Dorottya; Lakatos, Laszlo; Horvath, Agnes; Szita, Istvan; Pandur, Tunde; Mandel, Michael; Vegh, Zsuzsanna; Golovics, Petra Anna; Mester, Gabor; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos Sandor; Lakatos, Peter Laszlo

    2013-01-01

    AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn’s disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long

  11. Familial Adult-onset Alexander Disease: Clinical and Neuroradiological Findings of Three Cases

    PubMed Central

    ELMALI, Ayşe Deniz; ÇETİNÇELİK, Ümran; IŞLAK, Civan; UZUN ADATEPE, Nurten; KARAALİ SAVRUN, Feray; YALÇINKAYA, Cengiz

    2016-01-01

    The adult-onset Alexander disease (AOAD) dramatically differs from the early onset AD with respect to clinical and neuroradiological findings. Herein we report the detailed clinical and neuroradiological findings of a Turkish family with AOAD. In all three cases, magnetic resonance imaging revealed marked atrophy of the mesencephalon, bulbus, and cervical spinal cord accompanied with signal abnormalities in the same regions along with supratentorial white matter. Basal ganglia were affected in two cases. Molecular genetic analysis revealed heterozygous mutation in the 8th exon of the glial fibrillary acidic protein gene M451I (c.1245G>A), leading to the diagnosis of AOAD in all cases. PMID:28360791

  12. Adult-onset Still's disease revealed by perimyocarditis and a concomitant reactivation of an EBV infection

    PubMed Central

    Meckenstock, Roderich; Therby, Audrey; Gibault-Genty, Geraldine; Khau, David; Monnier, Sebastien; Greder-Belan, Alix

    2012-01-01

    We describe a 17-year-old patient presenting perimyocarditis as the initial manifestation of the adult-onset Still's disease. Corticotherapy was rapidly successful but induced major acute hepatitis in relation with Epstein-Barr virus reactivation. After 1 year, even if the global outcome is favourable, a slightly lowered ejection fraction still persists. Former case reports and differential diagnosis with reactive haemophagocytic syndrome would be discussed. PMID:23166163

  13. Chinese new immigrant mothers' perception about adult-onset non-communicable diseases prevention during childhood.

    PubMed

    Wang, Linda Dong Ling; Lam, Wendy Wing Tak; Wu, Joseph Tsz Kei; Fielding, Richard

    2015-12-01

    Many non-communicable diseases (NCDs) are largely preventable via behaviour change and healthy lifestyle, which may be best established during childhood. This study sought insights into Chinese new immigrant mothers' perceptions about adult-onset NCDs prevention during childhood. Twenty-three semi-structured interviews were carried out with new immigrant mothers from mainland China who had at least one child aged 14 years or younger living in Hong Kong. Interviews were audio taped, transcribed and analysed using a Grounded Theory approach. The present study identified three major themes: perceived causes of adult NCDs, beliefs about NCDs prevention and everyday health information practices. Unhealthy lifestyle, contaminated food and environment pollution were perceived as the primary causes of adult NCDs. Less than half of the participants recognized that parents had responsibility for helping children establish healthy behaviours from an early age to prevent diseases in later life. Most participants expressed helplessness about chronic diseases prevention due to lack of knowledge of prevention, being perceived as beyond individual control. Many participants experienced barriers to seeking health information, the most common sources of health information being interpersonal conversation and television. Participants' everyday information practice was passive and generally lacked awareness regarding early prevention of adult-onset NCDs. Updated understanding of this issue has notable implications for future health promotion interventions.

  14. Adult Onset Still's Disease: A Review on Diagnostic Workup and Treatment Options

    PubMed Central

    Gopalarathinam, Rajesh; Orlowsky, Eric; Kesavalu, Ramesh; Yelaminchili, Sreeteja

    2016-01-01

    Adult onset Still's disease (AOSD) is a rare systemic inflammatory disease of unknown etiology and pathogenesis that presents in 5 to 10% of patients as fever of unknown origin (FUO) accompanied by systemic manifestations. We report an interesting case of a 33-year-old African-American male who presented with one-month duration of FUO along with skin rash, sore throat, and arthralgia. After extensive workup, potential differential diagnoses were ruled out and the patient was diagnosed with AOSD based on the Yamaguchi criteria. The case history, incidence, pathogenesis, clinical manifestations, differential diagnoses, diagnostic workup, treatment modalities, and prognosis of AOSD are discussed in this case report. PMID:27042373

  15. Herpes Zoster Meningitis Complicating Combined Tocilizumab and Cyclosporine Therapy for Adult-Onset Still's Disease

    PubMed Central

    Tsurukawa, Shinichiro; Iwanaga, Nozomi; Izumi, Yasumori; Shirakawa, Atsunori; Kawahara, Chieko; Shukuwa, Tetsuo; Inamoto, Miwako; Kawakami, Atsushi; Migita, Kiyoshi

    2016-01-01

    A 56-year-old female with refractory adult-onset Still's disease presented with ocular herpes zoster infection during TCZ treatment. After three days of acyclovir treatment (5 mg/kg), she developed a severe headache and high fever. Viral DNA isolation and cerebral spinal fluid abnormalities led to a herpes zoster meningitis diagnosis. Her meningitis was cured by high doses of intravenous acyclovir (10 mg/kg for 14 days). To our knowledge, this is the first report of meningeal herpes zoster infection in rheumatic diseases under TCZ treatment. PMID:27092286

  16. Adult-onset Still's disease and chronic recurrent multifocal osteomyelitis: a hitherto undescribed manifestation of autoinflammation.

    PubMed

    Rech, J; Manger, B; Lang, B; Schett, G; Wilhelm, M; Birkmann, J

    2012-06-01

    Still's disease and chronic recurrent multifocal osteomyelitis (CRMO) are febrile rheumatic diseases of unknown etiology, which predominantly affect children but can also have their initial manifestation in adults. Both can present as intermittent, relapsing episodes and are considered potential candidates within the expanding spectrum of autoinflammatory disorders, although no genetic abnormalities have been described for either of them. Here, we describe a man with an initial manifestation of abacterial multifocal osteitis at the age of 41. During a relapsing-remitting course of his illness, he increasingly developed symptoms of adult-onset Still's disease (AOSD), and the diagnosis was established according to the Yamaguchi criteria. When treated with anakinra, not only the acute symptoms disappeared promptly, but also the osteitis went into complete remission. This is to our knowledge the first description of a simultaneous occurrence of these two manifestations of autoinflammation in adulthood.

  17. Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease Successfully Treated with Anakinra

    PubMed Central

    Kato, Hiroshi

    2016-01-01

    Macrophage activation syndrome (MAS) is a potentially fatal complication of Adult-Onset Still's disease (Still's disease). Whereas an increasing body of evidence supports interleukin-1 (IL-1) blockade as a promising treatment for Still's disease, whether it is therapeutic for MAS associated with Still's disease remains unclear. We report a 34-year-old Caucasian man with one-decade history of TNF-blockade-responsive seronegative arthritis who presented with abrupt onset of fever, serositis, bicytopenia, splenomegaly, hepatitis, and disseminated intravascular coagulation. Striking hyperferritinemia was noted without evidence of infection, malignancy, or hemophagocytosis on bone marrow biopsy. NK cells were undetectable in the peripheral blood, whereas soluble IL-2 receptor was elevated. His multiorgan disease resolved in association with methylprednisolone pulse therapy, Anakinra, and a tapering course of prednisone. This case reinforces the notion that Still's disease is inherently poised to manifest MAS as one of the clinical phenotypes by shedding light on the role of IL-1 underlying both Still's disease and related MAS. PMID:27818826

  18. Piriform sinus carcinoma with a paraneoplastic syndrome misdiagnosed as adult onset Still's disease: a case report.

    PubMed

    Yang, Liu; Li, Wen; Du, Jintao

    2015-01-01

    Paraneoplastic syndromes (PS) occur less commonly in association with otolaryngologic neoplasms than other carcinomas such as those of lung or breast. Piriform sinus carcinoma with PS is extremely rare. We here report a case of piriform sinus carcinoma accompanied by PS that was initially misdiagnosed as adult onset Still's disease and describe our diagnosis and treatment. One lesson we have drawn from the experience of this misdiagnosis is that PS symptoms may manifest before the primary tumor is evident and complicate the diagnostic process.

  19. Adult-onset Still disease with peculiar persistent plaques and papules.

    PubMed

    Yoshifuku, A; Kawai, K; Kanekura, T

    2014-06-01

    Adult-onset Still disease (AOSD) is a systemic inflammatory disorder characterized clinically by high spiking fever, polyarthralgia/arthritis, a salmon-pink evanescent rash, predominantly neutrophilic leucocytosis, lymphadenopathy, liver dysfunction, and splenomegaly. Recently, a nonclassic, nonevanescent skin rash has been reported. We report a 27-year-old woman with AOSD showing persistent pruritic papular lesions. Histologically, dyskeratotic keratinocytes were seen in the upper epidermis. We describe this case in detail and review the previous literature. Nonclassic pruritic eruptions with characteristic dyskeratotic keratinocytes might provide an important clue for the diagnosis of AOSD.

  20. Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still’s disease

    PubMed Central

    Wysocki, Jacek

    2016-01-01

    A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23rd day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still’s disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision. PMID:27826176

  1. Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still's disease.

    PubMed

    Gowin, Ewelina; Wysocki, Jacek

    2016-01-01

    A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23(rd) day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still's disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision.

  2. Adult-onset Still’s disease: current challenges and future prospects

    PubMed Central

    Siddiqui, Mariam; Putman, Michael S; Dua, Anisha B

    2016-01-01

    Adult-onset Still’s disease (AOSD) – a multi-systemic inflammatory condition characterized by high fevers, polyarthritis, an evanescent rash, and pharyngitis – has been a challenging condition to diagnose expediently and treat effectively. Questions remain regarding the underlying pathophysiology and etiology of AOSD. Pathognomonic diagnostic tests and reliable biomarkers remain undiscovered. Over the past decade, important progress has been made. Diagnostic criteria employing glycosylated ferritin have improved specificity. More important, novel biologic therapies have offered important clues to AOSD’s underlying pathophysiology. Cytokine-specific biologic therapies have been instrumental in providing more effective treatment for disease refractory to conventional treatment. While IL-1 therapy has demonstrated efficacy in refractory disease, novel therapies targeting IL-6 and IL-18 show great promise and are currently under investigation. PMID:27843366

  3. Hidden in plain sight: macrophage activation syndrome complicating Adult Onset Still's Disease.

    PubMed

    Benitez, Lourdes; Vila, Salvador; Mellado, Robert Hunter

    2010-01-01

    Hemophagocytic Lymphystiocytosis is a rare and fatal complication of rheumatic diseases, particularly Adult Onset Still's Disease (AOSD). It may be precipitated with immunosuppressive drugs and with viral and bacterial infections. A diagnosis depends on a high index of suspicion associated to certain clinical manifestations (fever, rash, Splemomegaly, any cytology blood dyscrasia, hipertrigliceridemia, hiperfibrinogenemia, and others), as well as pathologic evidence of hemophagocitosis from bone marrow biopsy or tissue samples of affected organs. Therapy consists of high dose corticosteroids and immunosuppressive drugs. We present a 42 year old woman with AOSD in remission who developed HLH in spite of receiving therapy with high dose steroids and immunosuppressive drugs. She had 2 negative bone marrow aspirates. Evidence of Hemophagocytosis was detected in both bone marrow biopsies. Timely evaluation and recognition of the signs and symptoms of HLH is crucial for the prompt management and a decrease in the mortality associated with this disease.

  4. The ocular motor features of adult-onset alexander disease: a case and review of the literature.

    PubMed

    Pfeffer, Gerald; Abegg, Mathias; Vertinsky, A Talia; Ceccherini, Isabella; Caroli, Francesco; Barton, Jason J S

    2011-06-01

    A 51-year-old Chinese man presented with gaze-evoked nystagmus, impaired smooth pursuit and vestibular ocular reflex cancellation, and saccadic dysmetria, along with a family history suggestive of late-onset autosomal dominant parkinsonism. MRI revealed abnormalities of the medulla and cervical spinal cord typical of adult-onset Alexander disease, and genetic testing showed homozygosity for the p.D295N polymorphic allele in the gene encoding the glial fibrillary acidic protein. A review of the literature shows that ocular signs are frequent in adult-onset Alexander disease, most commonly gaze-evoked nystagmus, pendular nystagmus, and/or oculopalatal myoclonus, and less commonly ptosis, miosis, and saccadic dysmetria. These signs are consistent with the propensity of adult-onset Alexander disease to cause medullary abnormalities on neuroimaging.

  5. Ethical and legal dilemmas arising during predictive testing for adult-onset disease: the experience of Huntington disease.

    PubMed Central

    Huggins, M; Bloch, M; Kanani, S; Quarrell, O W; Theilman, J; Hedrick, A; Dickens, B; Lynch, A; Hayden, M

    1990-01-01

    The goal of predictive testing is to modify the risk for currently healthy individuals to develop a genetic disease in the future. Such testing using polymorphic DNA markers has had major application in Huntington disease. The Canadian Collaborative Study of Predictive Testing for Huntington Disease has been guided by major principles of medical ethics, including autonomy, beneficence, confidentiality, and justice. Numerous ethical and legal dilemmas have arisen in this program, challenging these principles and occasionally casting them into conflict. The present report describes these dilemmas and offers our approach to resolving them. These issues will have relevance to predictive-testing programs for other adult-onset disorders. PMID:1971997

  6. A new structural approach to genomic discovery of disease: example of adult-onset diabetes.

    PubMed

    Sirovich, Lawrence

    2016-12-01

    This paper reports on an investigation of disease discovery from genomic data, by methods which depart substantially from customary practices found in the investigation of genome-wide association studies. Such data in general are composed of the genomic content from two contrasting phenotypes, e.g., disease versus control populations, and the analysis proceeds under the hypothesis that populational dissimilarities might reveal disease risk alleles. The proposed suite of new methods is in part based on information theory (Shannon in Bell Syst Tech J 27:379-423, 1948a; Bell Syst Tech J 27:623-656, 1948b; Jaynes in Phys Rev 106:620-630, 1957), and strong evidence will be given of the effectiveness of this new approach. The methodology extends naturally and successfully to predicting genomic disposition to disease arising from large collections of weakly contributing genomic loci. Evidence will be advanced that the example of adult-onset diabetes ("type 2 diabetes") is such a candidate disease, and in this case, probably for the first time, it can be demonstrated that disease prediction is possible. Another novel element of this study is the search and identification of potential beneficial genomic loci that may counter a disease. The generality of the methodology suggests that it might extend to other diseases.

  7. Occasional detection of thymic epithelial tumor 4 years after diagnosis of adult onset Still disease

    PubMed Central

    Lococo, Filippo; Bajocchi, Gianluigi; Caruso, Andrea; Valli, Riccardo; Ricchetti, Tommaso; Sgarbi, Giorgio; Salvarani, Carlo

    2016-01-01

    Abstract Background: Thymoma is a T cell neoplasm arising from the thymic epithelium that due to its immunological role, frequently undercover derangements of immunity such a tumors and autoimmune diseases. Methods: Herein, we report, to the best of our knowledge, the first description of an association between thymoma and adult onset Still disease (AOSD) in a 47-year-old man. The first one was occasionally detected 4 years later the diagnosis of AOSD, and surgically removed via right lateral thoracotomy. Histology confirmed an encapsulated thymic tumor (type AB sec. WHO-classification). Results: The AOSD was particularly resistant to the therapy, requiring a combination of immunosuppressant followed by anti-IL1R, that was the only steroids-sparing treatment capable to induce and maintain the remission. The differential diagnosis was particularly challenging because of the severe myasthenic-like symptoms that, with normal laboratory tests, were initially misinterpreted as fibromyalgia. The pathogenic link of this association could be a thymus escape of autoreactive T lymphocytes causing autoimmunity. Conclusion: Clinicians should be always include the possibility of a thymoma in the differential diagnosis of an unusual new onset of weakness and normal laboratories data, in particular once autoimmune disease is present in the medical history. PMID:27603335

  8. Adult onset retinoblastoma

    PubMed Central

    Sengupta, Sabyasachi; Pan, Utsab; Khetan, Vikas

    2016-01-01

    Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes. PMID:27609158

  9. Adult-onset Atopic Dermatitis

    PubMed Central

    Kanwar, Amrinder Jit

    2016-01-01

    Adult-onset atopic dermatitis is still an under recognized condition as there are only few studies regarding this entity. As compared to childhood onset atopic dermatitis, clinical features of adult onset atopic dermatitis are still not categorized. Adult atopic dermatitis can present for the first time in adult age with atypical morphology or may progress from childhood onset. This article reviews the characteristic clinical features of adult atopic dermatitis, associated risk factors and management. PMID:27904186

  10. Novel case of Trevor’s disease: Adult onset and later recurrence

    PubMed Central

    Khalsa, Amrit S; Kumar, Neil S; Chin, Matthew A; Lackman, Richard D

    2017-01-01

    Dysplasia epiphysealis hemimelica (DEH), or Trevor’s disease, is an osteocartilaginous epiphyseal overgrowth typically occurring in children. The literature reports 6 adult cases and none describe recurrence requiring additional procedures. We present a new-onset proximal tibial DEH in an adult recurring approximately 3 years after open excision. A 39-year-old female presented with a history of right knee pain, swelling, and instability. Physical examination revealed a firm proximal tibial mass. Computed tomography (CT) imaging showed an exophytic, lobulated, sclerotic mass involving the anterolateral margin of the lateral tibial plateau. Magnetic resonance imaging was suggestive of an osteochondroma. The patient underwent curettage of the lesion due to its periarticular location. Histology revealed benign and reactive bone and cartilage consistent with periosteal chondroma. Two and a half years later, the patient presented with a firm, palpable mass larger than the initial lesion. CT revealed a lateral tibial plateau sclerotic mass consistent with recurrent intra-articular DEH. A complete excision was performed and histology showed sclerotic bone with overlying cartilage consistent with exostosis. DEH is a rare epiphyseal osteocartilaginous outgrowth frequently occurring in the long bones of children less than 8 years old. DEH resembles an osteochondroma due to its pediatric presentation and similar histologic appearance. Adult-onset cases comprise less than 1% of reported cases. Recurrence rate after surgical intervention is unknown. Only 1 such case, occurring in a child, has been described. Clinicians contemplating operative treatment for DEH should note the potential for recurrence and consider complete excision. A follow-up period of several years may be warranted to identify recurrent lesions. PMID:28144583

  11. Clinical and histopathological features of cutaneous manifestations of adult-onset Still disease.

    PubMed

    Santa, Erin; McFalls, Jeanne M; Sahu, Joya; Lee, Jason B

    2017-03-25

    Adult-onset Still disease (AOSD) is a rare autoinflammatory syndrome characterized by recurring fevers, arthralgia, and consistent laboratory abnormalities that include leukocytosis and hyperferritinemia. Skin findings accompany the disease in nearly 90% of the cases. Early reports described evanescent, pruritic, salmon-pink or urticarial lesions, referred to as the typical eruption of AOSD. Histopathologic findings consist of superficial perivascular dermatitis with varying number of interstitial neutrophils. Later reports described a more persistent rash that tended to be photodistributed, hyperpigmented, often in a linear configuration, sometimes in a rippled pattern, referred to as the atypical eruption of AOSD. The presence of individual necrotic keratinocytes in the upper spinous layer has been the consistent histopathologic finding. The persistent rash may not represent an atypical presentation of AOSD as recent reports indicate a high prevalence of the rash. Emerging data also suggest that patients with persistent eruption have a worse prognosis. The recognition of the clinical and histopathological findings of skin eruptions of AOSD may facilitate an earlier diagnosis, potentially improving disease outcome. Herein, clinical and histopathological features of cutaneous manifestation of AOSD in two Asian women are highlighted accompanied by relevant review of the disease.

  12. Fever of unknown origin and leukemoid reaction as initial presentation of adult-onset Still's disease.

    PubMed

    Pardo-Cabello, Alfredo José; Manzano-Gamero, Victoria; Javier-Martínez, Rosario

    2014-01-01

    Adult Still's Disease has been reported as cause of Fever of Unknown Origin. Leukocytosis has been described as a common haematological abnormality in Adult Still's Disease. In some rare cases, leukemoid reaction has been reported associated to Still's Disease. We report the case of Adult Still's Disease presenting as Fever of Unknown Origin and leukemoid reaction in a patient with Down Syndrome. The patient needed high dosage of corticosteroids to control the disease and haematological findings.

  13. Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature.

    PubMed

    Pareyson, Davide; Fancellu, Roberto; Mariotti, Caterina; Romano, Silvia; Salmaggi, Andrea; Carella, Francesco; Girotti, Floriano; Gattellaro, Grazietta; Carriero, Maria Rita; Farina, Laura; Ceccherini, Isabella; Savoiardo, Mario

    2008-09-01

    Alexander disease (AD) in its typical form is an infantile lethal leucodystrophy, characterized pathologically by Rosenthal fibre accumulation. Following the identification of glial fibrillary acidic protein (GFAP) gene as the causative gene, cases of adult-onset AD (AOAD) are being described with increasing frequency. AOAD has a different clinical and neuroradiological presentation with respect to early-onset AD, as abnormalities are mainly concentrated in the brainstem-spinal cord junction. We report detailed clinical and genetic data of 11 cases of AOAD, observed over a 4-year period, and a review of the previously reported 25 cases of genetically confirmed AOAD. In our series, onset occurred as late as age 62, and up to 71 in an affected deceased relative. Most cases appeared sporadic, but family history may be misleading. The most frequent symptoms were related to bulbar dysfunction-with dysarthria, dysphagia, dysphonia (seven patients)-, pyramidal involvement (seven patients) and cerebellar ataxia (seven patients). Four patients had palatal myoclonus. Sleep disorders were also observed (four cases). Bulbar symptoms, however, were infrequent at onset and two symptomatic patients had an almost pure pyramidal involvement. Two subjects were asymptomatic. Misdiagnosis at presentation was frequent and MRI was instrumental in suggesting the correct diagnosis by showing, in all cases, mild to severe atrophy of the medulla oblongata extending caudally to the cervical spinal cord. In ten patients, molecular studies revealed six novel missense mutations and three previously reported changes in GFAP. The last typical patient carried no definitely pathogenic mutation, but a missense variant (p.D157N), supposedly a rare polymorphism. Revision of the literature and the present series indicate that the clinical picture is not specific, but AOAD must be considered in patients of any age with lower brainstem signs. When present, palatal myoclonus is strongly suggestive

  14. Adult-onset mitochondrial myopathy.

    PubMed Central

    Fernandez-Sola, J.; Casademont, J.; Grau, J. M.; Graus, F.; Cardellach, F.; Pedrol, E.; Urbano-Marquez, A.

    1992-01-01

    Mitochondrial diseases are polymorphic entities which may affect many organs and systems. Skeletal muscle involvement is frequent in the context of systemic mitochondrial disease, but adult-onset pure mitochondrial myopathy appears to be rare. We report 3 patients with progressive skeletal mitochondrial myopathy starting in adult age. In all cases, the proximal myopathy was the only clinical feature. Mitochondrial pathology was confirmed by evidence of ragged-red fibres in muscle histochemistry, an abnormal mitochondrial morphology in electron microscopy and by exclusion of other underlying diseases. No deletions of mitochondrial DNA were found. We emphasize the need to look for a mitochondrial disorder in some non-specific myopathies starting in adult life. Images Figure 1 Figure 2 PMID:1589382

  15. Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy.

    PubMed

    Sun, Natalie Z; Brezinski, Elizabeth A; Berliner, Jacqueline; Haemel, Anna; Connolly, M Kari; Gensler, Lianne; McCalmont, Timothy H; Shinkai, Kanade

    2015-08-01

    Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.

  16. Adult Still's disease

    MedlinePlus

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  17. Adult-onset Still's disease presenting as fever of unknown origin in a patient with HIV infection.

    PubMed

    DelVecchio, Sally; Skidmore, Peter

    2008-02-15

    A 43-year-old African American man with known human immunodeficiency virus (HIV) infection was found to have adult-onset Still's disease manifesting as fever of unknown origin. In the era of highly active antiretroviral therapy, HIV-infected patients are preserving their immune status and, thus, must be evaluated in a manner similar to that for the general population.

  18. Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function

    PubMed Central

    Figueroa-Bonaparte, Sebastián; Segovia, Sonia; Llauger, Jaume; Belmonte, Izaskun; Pedrosa, Irene; Alejaldre, Aída; Mayos, Mercè; Suárez-Cuartín, Guillermo; Gallardo, Eduard; Illa, Isabel; Díaz-Manera, Jordi

    2016-01-01

    Objectives Enzyme replacement therapy has shown to be effective for childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful for monitoring disease progression is one of the priority research topics in Pompe disease. Muscle MRI could be one possible test but the correlation between muscle MRI and muscle strength and function has been only partially addressed so far. Methods We studied 34 AOPD patients using functional scales (Manual Research Council scale, hand held myometry, 6 minutes walking test, timed to up and go test, time to climb up and down 4 steps, time to walk 10 meters and Motor Function Measure 20 Scale), respiratory tests (Forced Vital Capacity seated and lying, Maximun Inspiratory Pressure and Maximum Expiratory Pressure), daily live activities scales (Activlim) and quality of life scales (Short Form-36 and Individualized Neuromuscular Quality of Life questionnaire). We performed a whole body muscle MRI using T1w and 3-point Dixon imaging centered on thighs and lower trunk region. Results T1w whole body muscle MRI showed a homogeneous pattern of muscle involvement that could also be found in pre-symptomatic individuals. We found a strong correlation between muscle strength, muscle functional scales and the degree of muscle fatty replacement in muscle MRI analyzed using T1w and 3-point Dixon imaging studies. Moreover, muscle MRI detected mild degree of fatty replacement in paraspinal muscles in pre-symptomatic patients. Conclusion Based on our findings, we consider that muscle MRI correlates with muscle function in patients with AOPD and could be useful for diagnosis and follow-up in pre-symptomatic and symptomatic patients under treatment. Take home message Muscle MRI correlates with muscle function in patients with AOPD and could be useful to follow-up patients in daily clinic. PMID:27711114

  19. Stroke prevention by direct revascularization for patients with adult-onset moyamoya disease presenting with ischemia.

    PubMed

    Kim, Tackeun; Oh, Chang Wan; Kwon, O-Ki; Hwang, Gyojun; Kim, Jeong Eun; Kang, Hyun-Seung; Cho, Won-Sang; Bang, Jae Seung

    2016-06-01

    . CONCLUSIONS Direct or combined revascularization for patients with adult-onset moyamoya disease presenting with ischemia can prevent further stroke.

  20. Patient fibroblasts-derived induced neurons demonstrate autonomous neuronal defects in adult-onset Krabbe disease

    PubMed Central

    Choi, Won Jun; Oh, Ki-Wook; Nahm, Minyeop; Xue, Yuanchao; Choi, Jae Hyeok; Choi, Ji Young; Kim, Young-Eun; Chung, Ki Wha; Fu, Xiang-Dong; Ki, Chang-Seok; Kim, Seung Hyun

    2016-01-01

    Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by defective β-galactosylceramidase (GALC), a lysosomal enzyme responsible for cleavage of several key substrates including psychosine. Accumulation of psychosine to the cytotoxic levels in KD patients is thought to cause dysfunctions in myelinating glial cells based on a comprehensive study of demyelination in KD. However, recent evidence suggests myelin-independent neuronal death in the murine model of KD, thus indicating defective GALC in neurons as an autonomous mechanism for neuronal cell death in KD. These observations prompted us to generate induced neurons (iNeurons) from two adult-onset KD patients carrying compound heterozygous mutations (p.[K563*];[L634S]) and (p.[N228_S232delinsTP];[G286D]) to determine the direct contribution of autonomous neuronal toxicity to KD. Here we report that directly converted KD iNeurons showed not only diminished GALC activity and increased psychosine levels, as expected, but also neurite fragmentation and abnormal neuritic branching. The lysosomal-associated membrane proteins 1 (LAMP1) was expressed at higher levels than controls, LAMP1-positive vesicles were significantly enlarged and fragmented, and mitochondrial morphology and its function were altered in KD iNeurons. Strikingly, we demonstrated that psychosine was sufficient to induce neurite defects, mitochondrial fragmentation, and lysosomal alterations in iNeurons derived in healthy individuals, thus establishing the causal effect of the cytotoxic GALC substrate in KD and the autonomous neuronal toxicity in KD pathology. PMID:27780934

  1. Unique histopathologic findings in a patient with adult-onset Still disease.

    PubMed

    Wolgamot, Greg; Yoo, Jane; Hurst, Stan; Gardner, Greg; Olerud, John; Argenyi, Zsolt

    2007-04-01

    Adult-onset Still disease (AOSD) is an uncommon disorder characterized by fever, polyarthralgia, elevated white blood cell count, and a maculopapular rash, the histologic features of which have not been well-known. A 55-year-old Asian woman presented initially with a "burning" and severely pruritic eruption on her face, hands, and arms, thought clinically to be urticaria. Within 1 month, she began spiking high fevers, developed diffuse joint pain, and had marked elevations of ferritin, C-reactive protein, and erythrocyte sedimentation rate, characteristic of AOSD. The cutaneous eruption became more widespread, involving the trunk, scalp, and remainder of the extremities, with diffuse thickening of the skin with papular and linear hyperpigmentation and accentuation. Biopsies from several locations showed focal hyperkeratosis associated with dyskeratotic keratinocytes with a peculiar, distinctive distribution in the upper epidermis and cornified layers. In addition, increased dermal mucin was present, with minimal fibroblast proliferation and inflammation. This unusual combination of diffuse dermal mucinosis and a unique pattern of dyskeratosis can present a challenge in generating an accurate differential diagnosis, and may represent an unusual response to chronic scratching or be a distinctive histologic manifestation of AOSD.

  2. Serum calprotectin--a promising diagnostic marker for adult-onset Still's disease.

    PubMed

    Guo, Qian; Zha, Xicao; Li, Chun; Jia, Yuan; Zhu, Lei; Guo, Jianping; Su, Yin

    2016-01-01

    Calprotectin is a calcium-binding cytosolic protein, mainly expressed in immune cells, such as neutrophils, monocytes, and macrophages. Our study aimed to evaluate the diagnostic value of calprotectin for adult-onset Still's disease (AOSD), by comparing serum calprotectin concentrations in patients with AOSD (n = 46), rheumatoid arthritis (RA, n = 34), primary Sjögren syndrome (pSS, n = 40), systemic lupus erythematosus (SLE, n = 39), osteoarthritis (OA, n = 20), and healthy controls (HCs, n = 49). Calprotectin concentrations were significantly higher in patients with AOSD (55.26 ± 18.00 ng/ml), compared to patients with RA (39.17 ± 18.90 ng/ml), pSS (35.31 ± 19.47 ng/ml), SLE (32.21 ± 25.01 ng/ml), OA (19.24 ± 10.67 ng/ml), and HCs (8.46 ± 5.17 ng/ml). All the differences were highly significant (p < 0.001). Using receiver-operating characteristic curve, the cut-off value of calprotectin was defined as 45.488 ng/ml, and its sensitivity and specificity for AOSD diagnosis were 63.0 and 80.1%, respectively. The positive rate of calprotectin was significantly higher in AOSD cases compared to patients with other diseases and healthy controls (p < 0.001). Serum calprotectin was positively correlated with ferritin (r = 0.294, p < 0.05), and concentration of hemoglobin was significantly lower in calprotectin-positive patients compared to negative patients in AOSD (103.49 ± 20.21 g/l vs 115.71 ± 15.59 g/l, t = -2.142, p = 0.038). These findings suggest that serum calprotectin may serve as a promising marker for the diagnosis of AOSD and monitor disease activity to a certain extent.

  3. [Recurrent effusive pericarditis in the course of adult-onset Still's disease--case reports of two patients].

    PubMed

    Bilska, Anna; Wilińska, Ewelina; Szturmowicz, Monika; Wawrzyńska, Liliana; Fijałkowska, Anna; Oniszh, Karina; Swiatowiec, Andrzej; Wsół, Agnieszka; Torbicki, Adam

    2011-01-01

    Pericardial effusion is caused by various pathological agents. In differential diagnosis infectious as well as non-infectious factors have to be considered. Adult-onset Still disease (AOSD)--relatively uncommon systemic inflammatory disorder of unknown etiology--is among possible diagnosis. The disease typically affects patients in the age between 16-35 years and is characterized by spiking fever, arthralgia, evanescent salmon rash with other abnormalities including pharingitis, serositis (especially pleuritis and pericarditis) and leucocytosis as well as increased serum levels of inflammatory indicators. We present two patients with recurrent pericardial effusion in the course of AOSD.

  4. Adult-Onset Still’s Disease: Still a Serious Health Problem (a Case Report and Literature Review)

    PubMed Central

    Agha-Abbaslou, Mojgan; Bensaci, Ana Maria; Dike, Oluchi; Poznansky, Mark C.; Hyat, Arooj

    2017-01-01

    Patient: Female, 53 Final Diagnosis: Adult-onset Still’s Disease Symptoms: Abdominal pain • fever Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Rare disease Background: Adult-onset Still’s Disease (AOSD) is a rare systemic inflammatory disease accompanied by a triad of spiking fever, maculopapular exanthema, and arthralgia. To date, there is no definite laboratory or imaging test available for diagnosing AOSD, and the diagnosis is one of exclusion, which can be very challenging. Case Report: We report on the case of a 53-year-old female who presented with fever, arthralgia, and abdominal pain. Her initial laboratory tests showed elevated AST and ALT, and normal leukocytes with bandemia. During her hospitalization, we evaluated the patient for other potential differential diagnoses. After an extensive workup, the patient was diagnosed with AOSD based on Yamaguchi criteria. Her serum ferritin levels were measured and found to be markedly elevated, which is a non-specific finding in AOSD patients. Conclusions: This case highlights the important role of a detailed history and physical examination for timely diagnosis of AOSD to prevent complications and improve patient’s prognosis. PMID:28154368

  5. Inadvertent Skipping of Steroids in Septic Shock Leads to a Diagnosis of Adult Onset Still’s Disease

    PubMed Central

    Sethuraman, Vinoth K; Balasubramanian, Kavitha; Aghoram, Rajeswari

    2017-01-01

    Adult onset Still’s disease is uncommon in middle-aged and elderly individuals and can rarely present with shock; shock is usually associated with disseminated intravascular coagulation, multiorgan dysfunction syndrome or acute respiratory distress syndrome. We report a post-menopausal woman with arthritis, fever, pneumonitis and hypotension which was managed as septic shock. Steroids were inadvertently missed during the second day of hospitalization in the intensive care unit. Persistence of hypotension on inotropes, with normal renal, hepatic and neurological function and recurrence of fever when steroids were skipped, led to suspicion of an inflammatory disorder. A diagnosis of Still’s disease may be entertained in postmenopausal women with polyarthritis, rash, and fever with leukocytosis. Sepsis is mimicked, and multiple antibiotics use is common before the diagnosis of such an entity is made. Shock is rare in adult onset Still’s disease and is not necessarily associated with disseminated intravascular coagulation, acute respiratory distress syndrome, or multiorgan dysfunction. PMID:28191382

  6. The midlife cognitive profiles of adults at high risk of late-onset Alzheimer's disease: The PREVENT study.

    PubMed

    Ritchie, Karen; Carrière, Isabelle; Su, Li; O'Brien, John T; Lovestone, Simon; Wells, Katie; Ritchie, C W

    2017-03-29

    Although biomarker studies of late-onset Alzheimer's disease suggest pathology to be present decades before diagnosis, little is known about cognitive performance at this stage. A sample of 210 adults (aged 40-59) of whom 103 have a parent diagnosed with dementia (family history subgroup) underwent computerized cognitive testing. ApoE status was determined, and 193 subjects had magnetic resonance imaging. Distance from dementia onset was estimated in relation to age of parental diagnosis, and Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Scores were calculated. Lower hippocampal volumes (P = .04) were associated with poorer spatial location recall and higher Dementia Risk Scores with poorer visual recognition (P = .0005), and lower brain and hippocampal volume (P < .0001, P = .04, respectively). Family history subgroup participants closer to dementia onset had lower scores on visual working memory (P = .05), whereas those with an ApoE ε4 allele performed better on form perception (P = .005). Middle-aged adults at risk of dementia show evidence of poorer cognitive performance, principally in visuospatial functions.

  7. Adult-onset food allergy.

    PubMed

    Kivity, Shmuel

    2012-01-01

    The prevalence of food allergy is increasing in both the pediatric and adult populations. While symptom onset occurs mostly during childhood, there are a considerable number of patients whose symptoms first begin to appear after the age of 18 years. The majority of patients with adult-onset food allergy suffer from the pollen-plant allergy syndromes. Many of them manifest their allergy after exercise and consuming food to which they are allergic. Eosinophilic esophagitis, an eosinophilic inflammation of the esophagus affecting individuals of all ages, recently emerged as another allergic manifestation, with both immediate and late response to the ingested food. This review provides a condensed update of the current data in the literature on adult-onset allergy.

  8. Phenotypes, Risk Factors, and Mechanisms of Adult-Onset Asthma

    PubMed Central

    Ilmarinen, Pinja; Tuomisto, Leena E.; Kankaanranta, Hannu

    2015-01-01

    Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Genetic factors, atopy, and early respiratory tract infections are well-recognized factors predisposing to childhood-onset asthma. Adult-onset asthma is more often associated with obesity, smoking, depression, or other life-style or environmental factors, even though genetic factors and respiratory tract infections may also play a role in adult-onset disease. Adult-onset asthma is characterized by absence of atopy and is often severe requiring treatment with high dose of inhaled and/or oral steroids. Variety of risk factors and nonatopic nature of adult-onset disease suggest that variety of mechanisms is involved in the disease pathogenesis and that these mechanisms differ from the pathobiology of childhood-onset asthma with prevailing Th2 airway inflammation. Recognition of the mechanisms and mediators that drive the adult-onset disease helps to develop novel strategies for the treatment. The aim of this review was to summarize the current knowledge on the pathogenesis of adult-onset asthma and to concentrate on the mechanisms and mediators involved in establishing adult-onset asthma in response to specific risk factors. We also discuss the involvement of these mechanisms in the currently recognized phenotypes of adult-onset asthma. PMID:26538828

  9. Heterogeneity and frequency of movement disorders in juvenile and adult-onset Niemann-Pick C disease.

    PubMed

    Anheim, Mathieu; Lagha-Boukbiza, Ouhaïd; Fleury-Lesaunier, Marie-Céline; Valenti-Hirsch, Maria-Paola; Hirsch, Edouard; Gervais-Bernard, Hélène; Broussolle, Emmanuel; Thobois, Stéphane; Vanier, Marie T; Latour, Philippe; Tranchant, Christine

    2014-01-01

    Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.

  10. Acute pneumonitis in a patient with adult-onset disease after toclizumab treatment with good response to anakinra.

    PubMed

    Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Jara Chinarro, Beatriz; Espinosa Malpartida, María; Barbadillo Mateos, Carmen

    Pulmonary involvement in the form of acute pneumonitis in adult-onset Still's disease (AOSD) is an uncommon manifestation, with few cases reported in the literature. We report the case of a 61-year-old male with 3 years of AOSD evolution, treated with methotrexate (MTX) and half-dose corticosteroids, which debuted with symptoms of fever, dyspnea and dry cough after 3 weeks of receiving the first dose of tocilizumab (TCZ). In the follow-up study showed leukocytosis with left shift, elevated serum ferritin and C-reactive protein standard. The chest CT scan showed ground-glass pattern predominantly in central and upper lobes and the BAL shows an increase in the percentage of lymphocyte with normal subpopulations and negative cultures. MTX and TCM were suspended, prednisone was increased to 30mg/day and within a week Anakinra 100mg/day SC was iniciated, noting in a few days a progressive clinical, analytical and radiological improvement.

  11. Promotion of the Transition of Adult Patients with Childhood-Onset Chronic Diseases among Pediatricians in Japan.

    PubMed

    Ishizaki, Yuko; Higashino, Hirohiko; Kaneko, Kazunari

    2016-01-01

    The transition of adult patients with childhood-onset chronic diseases (APCCD) from pediatric to adult health-care systems has recently received worldwide attention. However, Japan is lagging behind European countries and North America as this concept of health-care transition was introduced only 10 years ago. In Japan, before the introduction of this concept, APCCD were referred to as "carryover patients," who were often considered a burden in pediatric practice. In the late 1990s, groups composed of pediatric nephrologists, developmental and behavioral pediatricians, pediatric nurses, and special education teachers researching the quality of life of adult patients with chronic kidney disease began to discuss the physical and psychosocial problems of APCCD. In 2006, a group of pediatricians first introduced the term "transition" in a Japanese journal. By 2010, a group of adolescent nurses had begun a specialized training program aimed at supporting patients during the transitional period. In 2013, the Ministry of Health, Labour and Welfare in Japan convened a research committee, focusing on issues related to social, educational, and medical support for APCCD, and the Japan Pediatric Society established a committee for the health-care transition of APCCD and summarized their statements. Moreover, in 2013, the Tokyo Metropolitan Children's Medical Center initiated ambulatory services for APCCD managed by specialized nurses. The concept of health-care transition has rapidly spread over these past 10 years. The purpose of this article is to describe how this concept of health-care transition has advanced in Japan, such that APCCD now experience a positive pediatric to adult health-care transition.

  12. Promotion of the Transition of Adult Patients with Childhood-Onset Chronic Diseases among Pediatricians in Japan

    PubMed Central

    Ishizaki, Yuko; Higashino, Hirohiko; Kaneko, Kazunari

    2016-01-01

    The transition of adult patients with childhood-onset chronic diseases (APCCD) from pediatric to adult health-care systems has recently received worldwide attention. However, Japan is lagging behind European countries and North America as this concept of health-care transition was introduced only 10 years ago. In Japan, before the introduction of this concept, APCCD were referred to as “carryover patients,” who were often considered a burden in pediatric practice. In the late 1990s, groups composed of pediatric nephrologists, developmental and behavioral pediatricians, pediatric nurses, and special education teachers researching the quality of life of adult patients with chronic kidney disease began to discuss the physical and psychosocial problems of APCCD. In 2006, a group of pediatricians first introduced the term “transition” in a Japanese journal. By 2010, a group of adolescent nurses had begun a specialized training program aimed at supporting patients during the transitional period. In 2013, the Ministry of Health, Labour and Welfare in Japan convened a research committee, focusing on issues related to social, educational, and medical support for APCCD, and the Japan Pediatric Society established a committee for the health-care transition of APCCD and summarized their statements. Moreover, in 2013, the Tokyo Metropolitan Children’s Medical Center initiated ambulatory services for APCCD managed by specialized nurses. The concept of health-care transition has rapidly spread over these past 10 years. The purpose of this article is to describe how this concept of health-care transition has advanced in Japan, such that APCCD now experience a positive pediatric to adult health-care transition. PMID:27803894

  13. Combination Immunosuppressive Therapy Including Rituximab for Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis in Adult-Onset Still's Disease

    PubMed Central

    Schäfer, Eva Johanna; Jung, Wolfram

    2016-01-01

    Hemophagocytic lymphopcytosis (HLH) is a life-threatening condition. It can occur either as primary form with genetic defects or secondary to other conditions, such as hematological or autoimmune diseases. Certain triggering factors can predispose individuals to the development of HLH. We report the case of a 25-year-old male patient who was diagnosed with HLH in the context of adult-onset Still's disease (AOSD) during a primary infection with Epstein-Barr virus (EBV). During therapy with anakinra and dexamethasone, he was still symptomatic with high-spiking fevers, arthralgia, and sore throat. His laboratory values showed high levels of ferritin and C-reactive protein. His condition improved after the addition of rituximab and cyclosporine to his immunosuppressive regimen with prednisolone and anakinra. This combination therapy led to a sustained clinical and serological remission of his condition. While rituximab has been used successfully for HLH in the context of EBV-associated lymphoma, its use in autoimmune diseases is uncommon. We hypothesize that the development of HLH was triggered by a primary EBV infection and that rituximab led to elimination of EBV-infected B-cells, while cyclosporine ameliorated the cytokine excess. We therefore propose that this combination immunosuppressive therapy might be successfully used in HLH occurring in the context of autoimmune diseases. PMID:28018698

  14. Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review.

    PubMed

    Ortiz-Sanjuán, Francisco; Blanco, Ricardo; Riancho-Zarrabeitia, Leyre; Castañeda, Santos; Olivé, Alejandro; Riveros, Anne; Velloso-Feijoo, María L; Narváez, Javier; Jiménez-Moleón, Inmaculada; Maiz-Alonso, Olga; Ordóñez, Carmen; Bernal, José A; Hernández, María V; Sifuentes-Giraldo, Walter A; Gómez-Arango, Catalina; Galíndez-Agirregoikoa, Eva; Blanco-Madrigal, Juan; Ortiz-Santamaria, Vera; del Blanco-Barnusell, Jordi; De Dios, Juan R; Moreno, Mireia; Fiter, Jordi; de los Riscos, Marina; Carreira, Patricia; Rodriguez-Valls, María J; González-Vela, M Carmen; Calvo-Río, Vanesa; Loricera, Javier; Palmou-Fontana, Natalia; Pina, Trinitario; Llorca, Javier; González-Gay, Miguel A

    2015-09-01

    Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations.

  15. Retrospective study of 61 patients with adult-onset Still's disease admitted with fever of unknown origin in China.

    PubMed

    Chen, Pei-Dong; Yu, Sheng-Lei; Chen, Shu; Weng, Xin-Hua

    2012-01-01

    Adult-onset Still's disease (AOSD), as a category of connective tissue diseases, has about 5∼9% of fever of unknown origin (FUO) cases. Diagnosis of AOSD was challenging because of its nonspecific characteristics. The present study analyzed clinical manifestations and laboratory findings in a series of patients with AOSD from eastern China. Medical records of 61 patients admitted with FUO and with a discharge diagnosis of AOSD were retrospectively evaluated and analyzed with special focus on clinical manifestations and laboratory findings. Compared with previous reports, most features of our patients had a similar incidence rate. Rash (79%), arthralgia (80%), and sore throat (84%) were the most frequent clinical manifestations in our series. Leukocytosis (80%), elevated ESR (98%) and CRP (100%), negative ANA (90%) and RF (93%), and high ferritin level (94%) were the most sensitive laboratory findings in our patients. AOSD was not a rare reason of FUO in eastern China. Fever, arthralgia, rash, sore throat, leukocytosis, neutrophilia, elevated ESR and CRP, negative ANA and RF, and high ferritin level were the most common clinical features in our series. The lack of highly specific characteristic makes the diagnosis of AOSD difficult compared with other diseases in FUO.

  16. Update on differences between childhood-onset and adult-onset systemic lupus erythematosus

    PubMed Central

    2013-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease and occurs worldwide in both children and adults. The estimated annual incidence among children is 2.22/100,000 and among adults is 23.2/100,000 in the United States. There is increasing understanding about differences in disease manifestations, medication use, and disease severity between those with childhood-onset SLE as compared with adult-onset SLE. Children have a more fulminant disease onset and course than adults with SLE, resulting in two to three times higher mortality. In future years, we anticipate more insight into the genetics between childhood-onset SLE and adult-onset SLE to help delineate the best therapies for both subsets of patients. PMID:23998441

  17. Inhibition of GSK-3 Ameliorates Aβ Pathology in an Adult-Onset Drosophila Model of Alzheimer's Disease

    PubMed Central

    Killick, Richard; Augustin, Hrvoje; Gandy, Carina; Allen, Marcus J.; Hardy, John; Lovestone, Simon; Partridge, Linda

    2010-01-01

    Aβ peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD), with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3) is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Aβ42 specifically in adult neurons, to avoid developmental effects. Aβ42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Aβ42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment) rescued Aβ42 toxicity. Aβ42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Aβ42. The GSK-3–mediated effects on Aβ42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Aβ42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Aβ42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Aβ42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD. PMID:20824130

  18. Quantitative analysis of upright standing in adults with late-onset Pompe disease

    PubMed Central

    Valle, Maria Stella; Casabona, Antonino; Fiumara, Agata; Castiglione, Dora; Sorge, Giovanni; Cioni, Matteo

    2016-01-01

    Pompe disease is a rare disorder producing muscle weakness and progressive impairments in performing daily motor activities, such as walking and standing. Most studies have focused on dysfunctions at cellular level, restricting the examination of gross motor functions to qualitative or subjective rating scales evaluations. With the aim of providing an instrumented quantification of upright standing in Pompe disease, we used a force platform to measure the center of pressure over three foot positions and with eyes open and closed. Amplitude and variability of body sway were measured to determine the level of postural stability, while power spectrum analysis and nonlinear computations were performed to explore the structure of the postural control. In comparison with healthy participants, patients with Pompe disease showed a reduced level of postural stability, but irrelevant variations in frequency content and spatio-temporal structure of the sway motion were detected. Changes in foot position did not increase the postural instability associated with Pompe disease, but prominent worsening occurred in the patients when they stand with eyes closed, particularly along the anterior-posterior direction. These results provide objective elements to monitor deficiencies of upright standing in Pompe disease, emphasizing the specific contributions of sway direction and sensory deficits. PMID:27845393

  19. Early Pathogenesis in the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

    PubMed Central

    van Zundert, Brigitte; Izaurieta, Pamela; Fritz, Elsa; Alvarez, Francisco J.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motor neurons starting in adulthood. Most of our knowledge about the pathophysiological mechanisms of ALS comes from transgenic mice models that emulate a subgroup of familial ALS cases (FALS), with mutations in the gene encoding superoxide dismutase (SOD1). In the more than 15 years since these mice were generated, a large number of abnormal cellular mechanisms underlying motor neuron degeneration have been identified, but to date this effort has led to few improvements in therapy, and no cure. Here, we consider that this surfeit of mechanisms is best interpreted by current insights that suggest a very early initiation of pathology in motor neurons, followed by a diversity of secondary cascades and compensatory mechanisms that mask symptoms for decades, until trauma and/or aging overloads their protective function. This view thus posits that adultonset ALS is the consequence of processes initiated during early development. In fact, motor neurons in neonatal mutant SOD mice display important alterations in their intrinsic electrical properties, synaptic inputs and morphology that are accompanied by subtle behavioral abnormalities. We consider evidence that human mutant SOD1 protein in neonatal hSOD1G93A mice instigates motor neuron degeneration by increasing persistent sodium currents and excitability, in turn altering synaptic circuits that control excessive motor neuron firing and leads to excitotoxicity. We also discuss how therapies that are aimed at suppressing abnormal neuronal activity might effectively mitigate or prevent the onset of irreversible neuronal damage in adulthood. PMID:22740507

  20. Clinical characteristics and follow-up analysis of adult-onset Still's disease complicated by hemophagocytic lymphohistiocytosis.

    PubMed

    Zhang, Yun; Yang, Yingyun; Bai, Yujia; Yang, Dan; Xiong, Yangyang; Zeng, Xuejun

    2016-05-01

    We evaluated clinical characteristics and prognosis for adult-onset Still's disease (AOSD) complicated by hemophagocytic lymphohistiocytosis (HLH). We retrospectively identified cases of AOSD with (n = 10) and without (n = 305) HLH complications. We reviewed their medical records, completed follow-up through outpatient clinic and telephone interviews, and analyzed their clinical symptoms, signs, laboratory test results, treatments, and prognosis. More AOSD patients with HLH developed hepatomegaly, bleeding, serositis, and neurologic symptoms than those without HLH, and they more commonly presented with leukopenia, thrombocytopenia, severe anemia, severe liver function abnormalities, decreased fibrinogen, elevated immunoglobulin, and bone marrow hemophagocytosis. The ten patients with AOSD complicated by HLH were treated with high-dose steroids or pulse steroid therapy, and eight of them also received cytotoxic drugs, while biological agents showed poor response. Follow-up results indicated that AOSD patients overall had good prognosis, while those with HLH showed worse prognosis, including higher relapse and readmission rates and increased mortality. In patients with AOSD, unexplained decreased blood cells, severe liver dysfunction, and/or hemophagocytosis in the bone marrow should be considered as signs of HLH complication. Patients with AOSD complicated by HLH have worse prognosis and higher relapse rates compared to AOSD patients without HLH complications. Thus, these patients should undergo frequent and careful follow-up.

  1. A series of 22 patients with adult-onset Still's disease presenting with fever of unknown origin. A difficult diagnosis?

    PubMed

    Baxevanos, Gerasimos; Tzimas, Thomas; Pappas, Georgios; Akritidis, Nikolaos

    2012-01-01

    Adult-onset Still's disease (AOSD) remains a perplexing, difficult to diagnose clinical entity, with clinical characteristics that are often broad and encountered in numerous other clinical entities. This vague clinical presentation is depicted in the commonly used diagnostic criteria, as the ones by Yamaguchi and Fautrel. The authors sought to investigate how diagnostic criteria apply in a series of 22 new cases of AOSD patients presenting with fever of unknown origin (FUO) and diagnosed at the Internal Medicine Department of Hatzikosta General Hospital of Ioannina, Greece. The aims of the study were: (1) to study the incidence of AOSD and (2) to retrospectively apply different classifications to the data of these patients in search of a more efficient way of diagnosing these patients in the future. The annual incidence of AOSD was estimated at two new cases per 10(5). The clinical manifestations of the patients are discussed, with an emphasis on specific manifestations being considered as criteria by Yamaguchi and Fautrel classifications. Four patients exhibited markedly increased serum D: -dimers, a finding of which the potential pathophysiologic implications are discussed. Serum ferritin levels have additive values, both for diagnostic and cost-reduction purposes in cases presenting as FUO; serum ferritin values are not included in any diagnostic set of criteria at present. The finding of high levels of D-dimers in AOSD needs further studies.

  2. Adult onset motor neuron disease: worldwide mortality, incidence and distribution since 1950.

    PubMed Central

    Chancellor, A M; Warlow, C P

    1992-01-01

    This review examines the commonly held premise that, apart from the Western Pacific forms, motor neuron disease (MND), has a uniform worldwide distribution in space and time; the methodological problems in studies of MND incidence; and directions for future epidemiological research. MND is more common in men at all ages. Age-specific incidence rises steeply into the seventh decade but the incidence in the very elderly is uncertain. A rise in mortality from MND over recent decades has been demonstrated wherever this has been examined and may be real rather than due to improved case ascertainment. Comparison of incidence studies in different places is complicated by non-standardised methods of case ascertainment and diagnosis but there appear to be differences between well studied populations. In developed countries in the northern hemisphere there is a weak positive correlation between standardised, age-specific incidence and distance from the equator. There is now strong evidence for an environmental factor as the cause of the Western Pacific forms of MND. A number of clusters of sporadic MND have been reported from developed countries, but no single agent identified as responsible. Images PMID:1479386

  3. Early rheumatoid disease. I. Onset.

    PubMed Central

    Fleming, A; Crown, J M; Corbett, M

    1976-01-01

    We describe features with onset in 102 patients seen within the first year of rheumatoid disease. The male:female ratio was approximately 3:4, suggesting a near equal sex incidence at onset. The disease started more often in the colder months and was usually insodious, symmetrical, and involved the upper limbs. The patients were followed prospectively and outcome was assessed after a mean of 4.5 years. Older patients fared worse and there was a trend for a poorer prognosis to be indicated by an insidious onset and early progression to symmetrical involvement. PMID:970994

  4. Adult onset asymmetric upper limb tremor misdiagnosed as Parkinson’s disease: A clinical and electrophysiological study

    PubMed Central

    Schwingenschuh, Petra; Ruge, Diane; Edwards, Mark J; Terranova, Carmen; Katschnig, Petra; Carrillo, Fatima; Silveira-Moriyama, Laura; Schneider, Susanne A; Kägi, Georg; Dickson, John; Lees, Andrew J; Quinn, Niall; Mir, Pablo; Rothwell, John C; Bhatia, Kailash P

    2010-01-01

    different from controls. Taken together, these results may help differentiate these SWEDDs patients from PD and support our hypothesis that adult-onset dystonia is the underlying diagnosis in this sub-group of patients with SWEDDs. PMID:20131394

  5. TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still’s Disease and Their Association with Disease Activity and Clinical Manifestations

    PubMed Central

    Kim, Hyoun-Ah; Han, Jae Ho; Kim, Woo-Jung; Noh, Hyun Jin; An, Jeong-Mi; Yim, Hyunee; Jung, Ju-Yang; Kim, You-Sun; Suh, Chang-Hee

    2016-01-01

    S100A8/A9 has been suggested as a marker of disease activity in patients with adult-onset Still’s disease (AOSD). We evaluated the clinical significance of S100A8/A9 as a biomarker and its pathogenic role in AOSD. Blood samples were collected prospectively from 20 AOSD patients and 20 healthy controls (HCs). Furthermore, skin and lymph node biopsy specimens of AOSD patients were investigated for S100A8/A9 expression levels via immunohistochemistry. Peripheral blood mononuclear cells (PBMCs) of active AOSD patients and HCs were investigated for S100A8/A9 cell signals. S100A8/A9, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in active AOSD patients were higher than those of HCs. S100A8/A9 levels correlated positively with IL-1β, TNF-α and C-reactive protein. The inflammatory cells expressing S100A8/A9 were graded from one to three in skin and lymph node biopsies of AOSD patients. The grading for S100A8/A9 was more intense in the skin lesions with karyorrhexis, mucin deposition, and neutrophil infiltration. Like lipopolysaccharide (LPS), S100A8/A9 induced phosphorylation of p38 and c-Jun amino-terminal kinase (JNK) in PBMCs, suggesting that S100A8/A9 activates Toll-like receptor 4 signaling pathways. These findings suggest that S100A8/A9 may be involved in the inflammatory response with induction of proinflammatory cytokines and may serve as a clinicopathological marker for disease activity in AOSD. PMID:27537874

  6. When uncommon and common coalesce: adult onset Still's disease associated with breast augmentation as part of autoimmune syndrome induced by adjuvants (ASIA).

    PubMed

    Dagan, A; Kogan, M; Shoenfeld, Y; Segal, G

    2016-06-01

    Adult onset Still's disease (AOSD) is an uncommon, multisystemic, auto-inflammatory disorder, while breast augmentation is a very common cosmetic procedure. We describe a case in which these two coalesce, AOSD, manifested with pleuritis and pericarditis, developed after breast mammoplasty. The pathogenetic, missing link, behind the development of AOSD following mammoplasty, is thought to be the autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). We reviewed other cases of AOSD associated with breast mammoplasty published to date and the literature regarding AOSD and ASIA syndrome. The review is followed by a short debate of whether silicone implants should be explanted in similar, future cases.

  7. The transition of adult patients with childhood-onset chronic diseases from pediatric to adult healthcare systems: a survey of the perceptions of Japanese pediatricians and child health nurses

    PubMed Central

    2012-01-01

    Background Advances in medical science have enabled many children with chronic diseases to survive to adulthood. The transition of adult patients with childhood-onset chronic diseases from pediatric to adult healthcare systems has received attention in Europe and the United States. We conducted a questionnaire survey among 41 pediatricians at pediatric hospitals and 24 nurses specializing in adolescent care to compare the perception of transition of care from pediatric to adult healthcare services for such patients. Findings Three-fourths of the pediatricians and all of the nurses reported that transition programs were necessary. A higher proportion of the nurses realized the necessity of transition and had already developed such programs. Both pediatricians and nurses reported that a network covering the transition from pediatric to adult healthcare services has not been established to date. Conclusions It has been suggested that spreading the importance of a transition program among pediatricians and developing a pediatric-adult healthcare network would contribute to the biopsychosocial well-being of adult patients with childhood-onset chronic disease. PMID:22433283

  8. Unusual early-onset Huntingtons disease.

    PubMed

    Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

    2003-06-01

    Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

  9. Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5years.

    PubMed

    Stepien, Karolina M; Hendriksz, Christian J; Roberts, Mark; Sharma, Reena

    2016-04-01

    Pompe disease is an autosomal recessive disease resulting from deficiency of the acid alpha-glucosidase (GAA). The late-onset Pompe Disease (LOPD) patients develop muscular and respiratory complications later in life. We describe a retrospective observational cohort study including 22 patients with LOPD. The cohort was assessed at baseline before Enzyme Replacement Therapy (ERT) with alglucosidase alpha (20mg/kg biweekly) was commenced and subsequently relevant information was collected at 2, 4 and 5years later. The median age of the patients at study entry was 44years (16-64years), with median disease duration of 11.5years (4-31years). At baseline, 10 patients (45%) could walk without support, 12 (55%) could walk with unilateral or bilateral support including 3/12 were wheelchair bound. Mean predicted FVC % was 55.7 (95% CI 45-66) of predicted normal at baseline and showed no significant change after 5years (54.6 (95% CI 43-66)), (all p=0.9815). Mean FVC % supine was 41.8 (95% CI 33.8-49) of predicted normal at baseline and remained significantly unchanged at 5years (48.4 (95% CI 37-59.6)), (all p=0.8680). The overnight non-invasive ventilator dependence increased by 18.2% as compared with baseline and requirement of mobility aids increased during this period by 5.2% as compared with the baseline. Mean walking distance at 6min walk test was 411.5 (95% CI 338-485) at baseline, 266.5 (95% CI 187-346) m at 2years, 238.6 (95% CI 162-315) m at 4years and 286.8 (95% CI 203-370) m at 5years (p=0.1981; ANOVA was completed only for 14 patients). A gradual decline in FVC% predicted was noted only in four cases and a decline in FVC% supine in two other. Only one patient showed a decline in both pulmonary function tests. In all remaining cases (17/22) respiratory function remains stable. In conclusion overall pulmonary function tests and mobility remained stable for 5years in majority of patients on ERT. However, in some patients they continued to decline in spite of ERT

  10. Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening

    PubMed Central

    Lazzeri, L.; Cammi, A.; Dragoni, F.

    2016-01-01

    Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P = 0.04; OR 0.4), stress at onset (P = 0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P = 0.003; OR = 0.23), and thyroid nodules (P = 0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P = 0.003; OR = 2.87) and Koebner phenomenon (P < 0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P = 0.014). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients. PMID:27747240

  11. Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening.

    PubMed

    Lazzeri, L; Colucci, R; Cammi, A; Dragoni, F; Moretti, S

    2016-01-01

    Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P = 0.04; OR 0.4), stress at onset (P = 0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P = 0.003; OR = 0.23), and thyroid nodules (P = 0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P = 0.003; OR = 2.87) and Koebner phenomenon (P < 0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P = 0.014). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients.

  12. An autopsied case of adult-onset bulbospinalform Alexander disease with a novel S393R mutation in the GFAP gene.

    PubMed

    Iwasaki, Yasushi; Saito, Yufuko; Mori, Keiko; Ito, Masumi; Mimuro, Maya; Aiba, Ikuko; Saito, Kozo; Mizuta, Ikuko; Yoshida, Tomokatsu; Nakagawa, Masanori; Yoshida, Mari

    2015-01-01

    A 50-year-old Japanese man with no apparent family history noticed diplopia. He gradually showed gait disturbance and dysuria. Abducens disorder of eye movement with nystagmus, tongue atrophy with fasciculation, spastic tetraparesis, and sensory disturbance were also observed. MRI showed severe atrophy of the medulla oblongata to the cervical cord ("tadpole appearance"). Tracheotomy and gastrostomy were performed 7 years after onset due to the development of bulbar palsy. Death occurred following respiratory failure after 11 years total disease duration. The brain weighed 1,380 g. The cerebrum, cerebellum, midbrain, and upper pons were preserved from atrophy, but the medulla oblongata to the cervical cord showed severe atrophy. A few Rosenthal fibers were observed in the cerebral white matter, basal ganglia, and cerebellum, whereas numerous Rosenthal fibers were observed in the medulla oblongata to the cervical cord. Myelin loss with relatively preserved axons was extensively observed from the middle of the pons to the spinal cord. The clinicopathological diagnosis was adult-onset bulbospinal-form Alexander disease. Glial fibrillary acidic protein (GFAP) gene analysis revealed a novel mutation of S393R. Expression patterns of S393R mutant GFAP using adrenal carcinoma-derived cells (SW13 cells) showed a decreased number of filamentous structures and abnormal aggregates.

  13. Etiopathogenesis and Therapeutic Approach to Adult Onset Acne

    PubMed Central

    Kaur, Sarabjit; Verma, Poonam; Sangwan, Ankita; Dayal, Surabhi; Jain, Vijay Kumar

    2016-01-01

    Acne vulgaris is usually considered as a skin disorder that primarily affects adolescents reaching a peak at the age of 14–17 years in females and 16–19 years in males. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. As it is regarded as a disease of teenagers, adults are more apprehensive and experience social anxiety. Hence, adult onset acne has become a matter of concern. PMID:27512185

  14. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L.

    PubMed

    Patel, Sheetal; Monemian, Seyed; Khalid, Ayesha; Dosik, Harvey

    2011-01-01

    Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  15. Highly Expression of CD11b and CD32 on Peripheral Blood Mononuclear Cells from Patients with Adult-Onset Still’s Disease

    PubMed Central

    Kim, Hyoun-Ah; Choi, Bunsoon; Suh, Chang-Hee; Han, Mi Hwa; Jung, Ju-Yang; Sayeed, Hasan M.; Kim, Ye Won; Sohn, Seonghyang

    2017-01-01

    Background: We investigated the potential role of several pattern-recognition receptors (PRRs; CD11b, CD11c, CD32, CD206, CD209, and dectin-1) in adult-onset Still’s disease (AOSD). Methods: The study included 13 untreated AOSD patients, 19 rheumatoid arthritis (RA) patients (as a disease control), and 19 healthy controls (HCs). The PRRs were quantified in peripheral blood using flow cytometry. The serum levels of interleukin-17 (IL-17), IL-18, and IL-23 were measured by enzyme-linked immunosorbent assay. Results: Significantly higher mean frequencies of cells presenting CD11b and CD32 from whole blood were observed in patients with AOSD than in patients with RA or HC. The levels of IL-17, IL-18, and IL-23 were elevated in AOSD patients compared to HCs. CD11b frequencies from whole cells correlated with systemic scores, lactate dehydrogenase (LDH) levels, aspartate transaminase levels, interleukin-23 (IL-23) levels, and IL-18. Frequencies of CD209 from granulocytes were significantly correlated with systemic scores, and the erythrocyte sedimentation rate and levels of C-reactive protein, ferritin, LDH, IL-23, and interleukin-18 (IL-18). Conclusions: Elevated frequencies of circulating CD11b-positive cells and positive correlations with disease activity markers suggest that circulating CD11b-positive cells contribute to the pathogenesis of AOSD. PMID:28106835

  16. Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis

    PubMed Central

    Chen, Der-Yuan; Hsieh, Chia-Wei; Chen, Hsin-Hua; Hung, Wei-Ting

    2016-01-01

    Objective Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still’s disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome. Methods Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites. Results Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05). Conclusion Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis. PMID

  17. Adult-onset opsoclonus-myoclonus syndrome.

    PubMed

    Klaas, James P; Ahlskog, J Eric; Pittock, Sean J; Matsumoto, Joseph Y; Aksamit, Allen J; Bartleson, J D; Kumar, Rajeev; McEvoy, Kathleen F; McKeon, Andrew

    2012-12-01

    BACKGROUND Little is known about adult-onset opsoclonus-myoclonus syndrome (OMS) outside of individual case reports. OBJECTIVE To describe adult-onset OMS. DESIGN Review of medical records (January 1, 1990, through December 31, 2011), prospective telephone surveillance, and literature review (January 1, 1967, through December 31, 2011). SETTING Department of Neurology, Mayo Clinic, Rochester, Minnesota. PATIENTS Twenty-one Mayo Clinic patients and 116 previously reported patients with adult-onset OMS. MAIN OUTCOME MEASURES Clinical course and longitudinal outcomes. RESULTS The median age at onset of the 21 OMS patients at the Mayo Clinic was 47 years (range, 27-78 years); 11 were women. Symptoms reported at the first visit included dizziness, 14 patients; balance difficulties, 14; nausea and/or vomiting, 10; vision abnormalities, 6; tremor/tremulousness, 4; and altered speech, 2. Myoclonus distribution was extremities, 15 patients; craniocervical, 8; and trunk, 4. Cancer was detected in 3 patients (breast adenocarcinoma, 2; and small cell lung carcinoma, 1); a parainfectious cause was assumed in the remainder of the patients. Follow-up of 1 month or more was available for 19 patients (median, 43 months; range, 1-187 months). Treatment (median, 6 weeks) consisted of immunotherapy and symptomatic therapy in 16 patients, immunotherapy alone for 2, and clonazepam alone for 1. Of these 19 patients, OMS remitted in 13 and improved in 3; 3 patients died (neurologic decline, 1; cancer, 1; and myocardial infarction, 1). The cause of death was of paraneoplastic origin in 60 of 116 literature review patients, with the most common carcinomas being lung (33 patients) and breast (7); the most common antibody was antineuronal nuclear antibody type 2 (anti-Ri, 15). Other causes were idiopathic in origin, 38 patients; parainfectious, 15 (human immunodeficiency virus, 7); toxic/metabolic, 2; and other autoimmune, 1. Both patients with N -methyl-D-aspartate receptor antibody had

  18. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43.

    PubMed

    Arnold, Eveline S; Ling, Shuo-Chien; Huelga, Stephanie C; Lagier-Tourenne, Clotilde; Polymenidou, Magdalini; Ditsworth, Dara; Kordasiewicz, Holly B; McAlonis-Downes, Melissa; Platoshyn, Oleksandr; Parone, Philippe A; Da Cruz, Sandrine; Clutario, Kevin M; Swing, Debbie; Tessarollo, Lino; Marsala, Martin; Shaw, Christopher E; Yeo, Gene W; Cleveland, Don W

    2013-02-19

    Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon degeneration and motor neuron death when expressed in mice at levels and in a cell type-selective pattern similar to endogenous TDP-43. Mutant TDP-43-dependent degeneration of lower motor neurons occurs without: (i) loss of TDP-43 from the corresponding nuclei, (ii) accumulation of TDP-43 aggregates, and (iii) accumulation of insoluble TDP-43. Computational analysis using splicing-sensitive microarrays demonstrates alterations of endogenous TDP-43-dependent alternative splicing events conferred by both human wild-type and mutant TDP-43(Q331K), but with high levels of mutant TDP-43 preferentially enhancing exon exclusion of some target pre-mRNAs affecting genes involved in neurological transmission and function. Comparison with splicing alterations following TDP-43 depletion demonstrates that TDP-43(Q331K) enhances normal TDP-43 splicing function for some RNA targets but loss-of-function for others. Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage.

  19. Vitiligo disease triggers: psychological stressors preceding the onset of disease.

    PubMed

    Silverberg, Jonathan I; Silverberg, Nanette B

    2015-05-01

    Vitiligo is the loss of skin pigmentation caused by autoimmune destruction of melanocytes. Little is known about the impact of psychological stressors preceding vitiligo onset on symptoms associated with vitiligo and the extent of disease. We performed a questionnaire-based study of 1541 adults with vitiligo to evaluate the impact of psychological stressors in this patient population. Psychological stressors should be considered as potential disease triggers in vitiligo patients, and screening of vitiligo patients for psychological stressors and associated symptoms should be included in routine assessment.

  20. Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.

    PubMed

    Oyanagi, Kiyomitsu; Kinoshita, Michiaki; Suzuki-Kouyama, Emi; Inoue, Teruhiko; Nakahara, Asa; Tokiwai, Mika; Arai, Nobutaka; Satoh, Jun-Ichi; Aoki, Naoya; Jinnai, Kenji; Yazawa, Ikuru; Arai, Kimihito; Ishihara, Kenji; Kawamura, Mitsuru; Ishizawa, Keisuke; Hasegawa, Kazuko; Yagisita, Saburo; Amano, Naoji; Yoshida, Kunihiro; Terada, Seishi; Yoshida, Mari; Akiyama, Haruhiko; Mitsuyama, Yoshio; Ikeda, Shu-Ichi

    2016-09-08

    The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N-HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N-HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of axons in ALSP.

  1. Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a Rare Entity With a Strong Link to IgG4-Related Disease: An Observational Case Report Study.

    PubMed

    London, Jonathan; Martin, Antoine; Soussan, Michael; Badelon, Isabelle; Gille, Thomas; Uzunhan, Yurdagul; Giroux-Leprieur, Bénédicte; Warzocha, Ursula; Régent, Alexis; Galatoire, Olivier; Dhote, Robin; Abad, Sébastien

    2015-10-01

    Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells. Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients. It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs.To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX. Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled. Biopsies from ocular adnexa or other organs were systematically reexamined. For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed.Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD. One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD.These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria. To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome.

  2. Season of Birth and Risk for Adult Onset Glioma

    PubMed Central

    Efird, Jimmy T.

    2010-01-01

    Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive. PMID:20623001

  3. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43

    PubMed Central

    Arnold, Eveline S.; Ling, Shuo-Chien; Huelga, Stephanie C.; Lagier-Tourenne, Clotilde; Polymenidou, Magdalini; Ditsworth, Dara; Kordasiewicz, Holly B.; McAlonis-Downes, Melissa; Platoshyn, Oleksandr; Parone, Philippe A.; Da Cruz, Sandrine; Clutario, Kevin M.; Swing, Debbie; Tessarollo, Lino; Marsala, Martin; Shaw, Christopher E.; Yeo, Gene W.; Cleveland, Don W.

    2013-01-01

    Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43Q331K and TDP-43M337V), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon degeneration and motor neuron death when expressed in mice at levels and in a cell type-selective pattern similar to endogenous TDP-43. Mutant TDP-43-dependent degeneration of lower motor neurons occurs without: (i) loss of TDP-43 from the corresponding nuclei, (ii) accumulation of TDP-43 aggregates, and (iii) accumulation of insoluble TDP-43. Computational analysis using splicing-sensitive microarrays demonstrates alterations of endogenous TDP-43–dependent alternative splicing events conferred by both human wild-type and mutant TDP-43Q331K, but with high levels of mutant TDP-43 preferentially enhancing exon exclusion of some target pre-mRNAs affecting genes involved in neurological transmission and function. Comparison with splicing alterations following TDP-43 depletion demonstrates that TDP-43Q331K enhances normal TDP-43 splicing function for some RNA targets but loss-of-function for others. Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage. PMID:23382207

  4. Adult onset pigmentary orthochromatic leukodystrophy with ovarian dysgenesis.

    PubMed

    Verghese, J; Weidenheim, K; Malik, S; Rapin, I

    2002-11-01

    Pigmentary type of orthochromatic leukodystrophy (POLD) is an adult-onset leukodystrophy, characterized pathologically by the presence of glial and microglial cytoplasmic pigment inclusions. The complete phenotype, genotype and pathogenetic mechanisms in POLD have not been elucidated. We followed for 18 years a woman with autopsy-proven POLD, who presented with 'frontal' dementia and spasticity. Her further course was marked by progressive mutism, apraxia and seizures. Her sister had died of the same disease after a much more rapidly progressing course. These sisters had primary infertility with pathologic evidence of streak ovaries. Diagnosis was confirmed in both cases by post-mortem examination. POLD is a rare cause of adult-onset leukodystrophy presenting with dementia. Ovarian dysgenesis is extremely rare in the absence of demonstrable chromosomal abnormalities and extends the clinical spectrum of POLD.

  5. Adult-onset acute rheumatic fever.

    PubMed

    Nakashima, Dainari; Ueda, Kohei; Tsukuda, Kyozo; Utsu, Noriaki; Kohki, Shimazu; Fushimi, Hiroaki; Miyakoshi, Kazuho

    2012-01-01

    A 62-year-old man was hospitalized for acute rheumatic fever. He had previously suffered from rheumatic fever at 15 years of age. The rheumatic fever was complicated by carditis, which caused valve disease that required surgical treatment. The incidence of rheumatic fever has decreased in most developed countries with improvements in sanitary conditions. The low incidence of this disease makes a timely and accurate diagnosis difficult. Due to the fact that both the first occurrence and recurrence of acute rheumatic fever can occur in the elderly and adults, this potential disease should not be overlooked when making a differential diagnosis.

  6. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    ERIC Educational Resources Information Center

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

  7. Age-at-onset in Huntington disease

    PubMed Central

    Orth, Michael; Schwenke, Carsten

    2011-01-01

    Background: In Huntington disease, the accurate determination of age-at-onset is critical to identify modifiers and therapies that aim to delay it. Methods: Retrospective data from the European Huntington’s Disease Network’s REGISTRY and PREDICT-HD, a longitudinal study in prodromal huntingtin gene expansion mutation carriers. Data (age, gender, CAG repeat length, parent affected, and Unified Huntington’s Disease Rating Scale motor score, total functional capacity) from at least three visits in 423 REGISTRY and 124 PREDICT-HD participants were included. Data based extrapolations of individual age-at-onset using generalized linear mixed models based on individual slopes of motor score or total functional capacity, and predictions using the Langbehn, or Ranen formula, were compared with clinicians’ estimates. Results: Concordance was best for the observed age-at-onset in PREDICT-HD and the calculated onset using the PREDICT-HD UHDRS longitudinal motor scores. This was superior to the REGISTRY data. For total functional capacity, the investigator’s estimate was 4 years before the data derived age-at-onset. The concordance of predictions of probability of age-at-onset is better with the observed age-at-onset in the PREDICT-HD data (difference in 25%tile -5 to 10 years) than the REGISTRY data (±20 years). Conclusions: Estimating or predicting age-at-onset in Huntington disease may be inaccurate. It can be useful to 1) add in the manifest population motor score regression derived age-at-onset as additional motor onset and 2) add total functional capacity regression derived age-at-onset for the onset of functional impact of Huntington disease when patients are in mid- to late-stage. PMID:22453877

  8. Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy

    PubMed Central

    Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

    2016-01-01

    Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD. PMID:28035995

  9. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  10. New onset of idiopathic bilateral ear tics in an adult.

    PubMed

    Agrawal, Amit; Shrestha, Rabin

    2009-04-01

    Tic disorders are commonly considered to be childhood syndromes. Newly presenting tic disorders during adulthood are uncommon and mostly described in relation to an acquired brain lesion or as incidental tics, particularly in context with other neurological or psychiatric diseases. Tic disorder involving the ears is extremely uncommon with only few studies in English literature. In the present case, we describe an adult patient with new-onset idiopathic tics disorder involving both ears, causing social embarrassment. In addition, our patient had recent onset of the tics without any childhood or family history of tic disorders. The single most important component of management is an accurate diagnosis. At the same time, tics should be differentiated from other movement disorders such as chorea, stereotypy, and dystonias.

  11. Early-onset Lafora body disease

    PubMed Central

    Turnbull, Julie; Girard, Jean-Marie; Lohi, Hannes; Chan, Elayne M.; Wang, Peixiang; Tiberia, Erica; Omer, Salah; Ahmed, Mushtaq; Bennett, Christopher; Chakrabarty, Aruna; Tyagi, Atul; Liu, Yan; Pencea, Nela; Zhao, XiaoChu; Scherer, Stephen W.; Ackerley, Cameron A.

    2012-01-01

    The most common progressive myoclonus epilepsies are the late infantile and late infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6 years), Unverricht–Lundborg disease (onset after the age of 6 years) and Lafora disease. Lafora disease is a distinct disorder with uniform course: onset in teenage years, followed by progressively worsening myoclonus, seizures, visual hallucinations and cognitive decline, leading to a vegetative state in status myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are pathognomonic and not seen with any other progressive myoclonus epilepsies. Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen molecules with inordinately long strands that render them insoluble. Lafora disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically active enzymes that regulate glycogen construction, ensuring symmetric expansion into a spherical shape, essential to its solubility. In this work, we report a new progressive myoclonus epilepsy associated with Lafora bodies, early-onset Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and mutation and characterize the relationship of its gene product with laforin and malin. Early-onset Lafora body disease presents early, at 5 years, with dysarthria, myoclonus and ataxia. The combination of early-onset and early dysarthria strongly suggests late infantile-variant neuronal ceroid lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis, but Lafora bodies. The subsequent course is a typical progressive myoclonus epilepsy, though much more protracted than any infantile neuronal ceroid lipofuscinosis, or Lafora disease, patients living into the fourth decade. The mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show that the PRDM8 protein interacts with laforin and malin and

  12. Interleukin 6 SNP rs1800797 associates with the risk of adult-onset asthma.

    PubMed

    Lajunen, T K; Jaakkola, J J K; Jaakkola, M S

    2016-04-01

    Interleukin 6 (IL6) is an inflammatory cytokine that has been suggested to have an important role in the pathogenesis of asthma. IL6 single-nucleotide polymorphisms (SNPs) have been associated with levels of IL6, and with childhood and prevalent adult asthma. A recent study also suggested that IL6 SNPs associate especially with atopic asthma. However, association of IL6 SNPs with adult-onset asthma has not been studied. In a population-based study of 467 incident adult-onset asthma cases and 613 disease-free controls from South Finland, we analyzed association of 6 tagging SNPs of the IL6 locus with the risk of adult-onset asthma and with atopy. Asthma was clinically diagnosed, and atopy was defined based on Phadiatop test. IL6 SNP rs1800797 associated with the risk of adult-onset asthma in a log additive model, with adjusted odds ratio (aOR) 1.31 (95% confidence interval 1.09-1.57), and especially with the risk of atopic adult-onset asthma when compared with non-atopic controls, aOR 1.46 (95% CI 1.12-1.90). This is the first study to show an association of IL6 with adult-onset asthma, and especially with atopic adult-onset asthma.

  13. Is Adolescent-Onset First-Episode Psychosis Different from Adult Onset?

    ERIC Educational Resources Information Center

    Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

    2005-01-01

    Objective: To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Method: Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated…

  14. The Scottish Motor Neuron Disease Register: a prospective study of adult onset motor neuron disease in Scotland. Methodology, demography and clinical features of incident cases in 1989.

    PubMed Central

    1992-01-01

    The Scottish Motor Neuron Disease Register (SMNDR) is a prospective, collaborative, population based study of motor neuron disease (MND) in Scotland. The register started in January 1989 with the aim of studying the clinical and epidemiological features of MND by prospectively identifying incident patients. It is based on a system of registration by recruitment from multiple sources, followed by the collection of complete clinical data and follow up, mainly through general practitioners. In this report the register's methodology and the demography and incidence data for the first year of study are presented. One hundred and fourteen newly diagnosed patients were identified in 1989 giving a crude incidence for Scotland of 2.24/100,000/year. Standardised incidence ratios showed a non-significant trend towards lower rates in north eastern regions and island areas. PMID:1640227

  15. Voice Onset Time in Parkinson Disease

    ERIC Educational Resources Information Center

    Fischer, Emily; Goberman, Alexander M.

    2010-01-01

    Research has found that speaking rate has an effect on voice onset time (VOT). Given that Parkinson disease (PD) affects speaking rate, the purpose of this study was to examine VOT with the effect of rate removed (VOT ratio), along with the traditional VOT measure, in individuals with PD. VOT and VOT ratio were examined in 9 individuals with PD…

  16. Huntington's disease: prenatal screening for late onset disease.

    PubMed Central

    Post, S G

    1992-01-01

    This article presents a set of moral arguments regarding the selective abortion of fetuses on the basis of prenatal screening for late onset genetic diseases only, and for Huntington's Disease* in particular. After discussion of human suffering, human perfection and the distinctive features of the lives of people confronting late onset genetic disease, the author concludes that selective abortion is difficult to justify ethically, although it must remain a matter of personal choice. PMID:1535662

  17. Huntington's disease: prenatal screening for late onset disease.

    PubMed

    Post, S G

    1992-06-01

    This article presents a set of moral arguments regarding the selective abortion of fetuses on the basis of prenatal screening for late onset genetic diseases only, and for Huntington's Disease* in particular. After discussion of human suffering, human perfection and the distinctive features of the lives of people confronting late onset genetic disease, the author concludes that selective abortion is difficult to justify ethically, although it must remain a matter of personal choice.

  18. Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

    PubMed

    Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

    2016-07-01

    Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis.

  19. Niemann-Pick type C: focus on the adolescent/adult onset form.

    PubMed

    Di Lazzaro, Vincenzo; Marano, Massimo; Florio, Lucia; De Santis, Stefano

    2016-11-01

    Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment.

  20. Young-onset parkinsonism in a Hong Kong Chinese man with adult-onset Hallervorden-Spatz syndrome.

    PubMed

    Mak, Chloe Miu; Sheng, Bun; Lee, Hencher Han-chih; Lau, Kwok-kwong; Chan, Wing-tak; Lam, Ching-wan; Chan, Yan-wo

    2011-04-01

    Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of disorders varied in genetic etiologies, clinical presentations, and radiological features. NBIA is an iron homeostasis disorder with progressive iron accumulation in the central nervous systems and is clinically characterized by extrapyramidal movement abnormalities, retinal pigmentary changes, and cognitive impairment. Panthothenate kinase-associated neurodegeneration (Hallervorden-Spatz disease) is the commonest disorder of NBIA with a prevalence of one-three per million. Clinically, it is classified into early-onset childhood, atypical late-onset, and adult-onset type. Adult-onset type is rarer. We report the first case of adult-onset panthothenate kinase-associated neurodegeneration in Hong Kong in a 28-year-old Chinese man who presented with pure young-onset parkinsonism. Magnetic resonance imaging (MRI) of the brain showed the presence of eye-of-the-tiger sign. Two compound heterozygous mutations PANK2 NM_153638.2: c.445G > T; NP_705902.2: p.E149X and PANK2 NM_153638.2: c.1133A > G; NP_705902.2: p.D378G were detected. Parkinsonism per se is a very heterogeneous phenotypic group. In view of the readily available genetic analysis of PANK2, panthothenate kinase-associated neurodegeneration should be considered in adult patients with young-onset parkinsonism with or without the eye-of-the-tiger sign. The exact diagnosis offers a different management approach and genetic counseling. NBIA is likely under- or misdiagnosed in Hong Kong Chinese.

  1. Adult-onset idiopathic chondrolysis of the hip.

    PubMed

    Yapp, Liam Z; McClymont, Liusaidh; Beggs, Ian; Gaston, Paul; Salter, Donald M

    2017-05-01

    We report the case of a 23-year-old man diagnosed with adult-onset idiopathic chondrolysis of the hip. Chondrolysis of the hip is a disorder most frequently seen in children who have suffered with slipped capital femoral epiphyses. Idiopathic chondrolysis of the hip is extremely rare and to our knowledge, its onset has never been documented in adults aged over 20. With reference to the available medical literature, we summarise the current clinical management of this unusual but important cause of young adult hip pain.

  2. Functional and Structural Analyses of CYP1B1 Variants Linked to Congenital and Adult-Onset Glaucoma to Investigate the Molecular Basis of These Diseases

    PubMed Central

    Chakrabarti, Saikat; Ray, Kunal

    2016-01-01

    Glaucoma, the leading cause of irreversible blindness, appears in various forms. Mutations in CYP1B1 result in primary congenital glaucoma (PCG) by an autosomal recessive mode of inheritance while it acts as a modifier locus for primary open angle glaucoma (POAG). We investigated the molecular basis of the variable phenotypes resulting from the defects in CYP1B1 by using subclones of 23 CYP1B1 mutants reported in glaucoma patients, in a cell based system by measuring the dual activity of the enzyme to metabolize both retinol and 17β-estradiol. Most variants linked to POAG showed low steroid metabolism while null or very high retinol metabolism was observed in variants identified in PCG. We examined the translational turnover rates of mutant proteins after the addition of cycloheximide and observed that the levels of enzyme activity mostly corroborated the translational turnover rate. We performed extensive normal mode analysis and molecular-dynamics-simulations-based structural analyses and observed significant variation of fluctuation in certain segmental parts of the mutant proteins, especially at the B-C and F-G loops, which were previously shown to affect the dynamic behavior and ligand entry/exit properties of the cytochrome P450 family of proteins. Our molecular study corroborates the structural analysis, and suggests that the pathologic state of the carrier of CYP1B1 mutations is determined by the allelic state of the gene. To our knowledge, this is the first attempt to dissect biological activities of CYP1B1 for correlation with congenital and adult onset glaucomas. PMID:27243976

  3. An atypical presentation of adult-onset Still’s disease complicated by pulmonary hypertension and macrophage activation syndrome treated with immunosuppression: a case-based review of the literature

    PubMed Central

    Manson, Daniel K.; Horn, Evelyn M.; Haythe, Jennifer

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a known complication of rheumatologic diseases, but it is only rarely associated with adult-onset Still’s disease (AOSD). We describe the case of a 30-year-old woman who presented in a pulmonary hypertension crisis and was found to have underlying AOSD with PAH and nonspecific interstitial pneumonia (NSIP) with a course complicated by macrophage activation syndrome (MAS). She dramatically improved with steroids, cyclosporine A, and anakinra, with total resolution of the MAS and significant improvement of her pulmonary arterial pressures. While there are only select case reports of AOSD associated with PAH, this is the first reported case of (1) AOSD complicated by both PAH and MAS and (2) AOSD complicated by biopsy-proven NSIP. Clinically, this case highlights the efficacy of immunosuppressive agents in the treatment of PAH and MAS from underlying AOSD and supports their use in this setting. PMID:27162622

  4. Adult-onset amenorrhea: a study of 262 patients.

    PubMed

    Reindollar, R H; Novak, M; Tho, S P; McDonough, P G

    1986-09-01

    A series of 262 patients with amenorrhea of adult onset are reported. Hypothalamic suppression followed by inappropriate positive feedback, and then hyperprolactinemia and ovarian failure are the most frequently encountered etiologies. Other etiologies are diverse and numerically less frequent. Amenorrhea after use of oral contraceptives, or postpill amenorrhea, occurred in 77 (29%) of all patients. The average age of presentation, prior menstrual history, associated morbidity, and subsequent reproductive potential of each diagnostic group are reported. Adult-onset amenorrhea has a less significant impact on future wellbeing than was reported for a similar-sized group of patients whose amenorrhea developed as a result of pubertal aberrancy.

  5. Cystic fibrosis lung disease in adult patients.

    PubMed

    Vender, Robert L

    2008-04-01

    As the longevity of all patients with cystic fibrosis (CF) continues to increase (median 2005 survival=36.8 years), more adult patients will be receiving their medical care from nonpediatric adult-care providers. Cystic fibrosis remains a fatal disease, with more than 80% of patients dying after the age of 18 years, and most deaths resulting from pulmonary disease. The changing epidemiology requires adult-care providers to become knowledgeable and competent in the clinical management of adults with CF. Physicians must understand the influence of specific genotype on phenotypic disease presentation and severity, the pathogenic factors determining lung disease onset and progression, the impact of comorbid disease factors such as CF-related diabetes and malnutrition upon lung disease severity, and the currently approved or standard accepted therapies used for chronic management of CF lung disease. This knowledge is critical to help alleviate morbidity and improve mortality for the rapidly expanding population of adults with CF.

  6. Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome

    PubMed Central

    Shen, Guohua; Zhang, Yuwei; Hu, Shuang; Liu, Bin; Kuang, Anren

    2017-01-01

    Abstract Rationale: Hypophosphatemic osteomalacia (HO) is a metabolic bone disease, exhibiting different etiologies such as genetic mutation, tumor induction, dysimmunity, or renal disease. Sjogren's syndrome (SS) is a connective tissue disorder commonly involving exocrine glands; however kidney involvement is also encountered, leading to abnormal phosphorus metabolism, even HO. Patient concerns: A 47-year-old female patient presented progressively worsening pain in the chest wall, back and bilateral lower extremities as well as muscle weakness was referred to our department. Diagnoses, interventions and outcomes: Due to the laboratory test results, radiographic findings and pathologic results, she was diagnosed with adult-onset HO associated with SS. She was then treated with alkalinization, steroids, neutral phosphate, calcium supplements together with activated vitamin D. So far, she recovered uneventfully with relieved pain and increased serum phosphorus level. Lessons: HO may be secondary to renal tubular acidosis of SS patients, and it might be a diagnostic challenge when the kidney involvement in SS is latent and precede the typical sicca symptoms. PMID:28353596

  7. Juvenile onset Huntington's disease--clinical and research perspectives.

    PubMed

    Nance, M A; Myers, R H

    2001-01-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder. The mutation which causes the disease is an expansion in the number of repetitions of three nucleotides, C, A, and G in exon 1 of the huntingtin gene. The gene normally has 15 to 30 repeats and an expansion to 40 or more is associated with HD. HD usually has a mid-life onset, but a juvenile form, defined by onset of symptoms before the age of 21 years, is present in about 7% of HD cases. Juvenile HD is characterized by (1) transmission from an HD affected father, (2) an unusually large repeat size, usually of 60 or more units, and (3) unique clinical features, including rigidity and seizure disorder. Although juvenile onset is associated with a more severe neuropathological involvement, the neuropathological characteristics of juvenile HD are similar to those seen in the adult form in that the striatum bears the brunt of the illness. Clumps of protein, termed inclusion bodies, which stain positive for huntingtin and ubiquitin, are found primarily in the nucleus but also in the cytoplasm and axons in HD neurons. Research suggests that these inclusion bodies sequester a deleterious protein fragment and prolong cell life during the degenerative process of the disease.

  8. Clinical profile of patients with adult-onset eosinophilic asthma

    PubMed Central

    Storm, Huib; Amelink, Marijke; de Nijs, Selma B.; Eichhorn, Edwin; Reitsma, Bennie H.; Bel, Elisabeth H.D.; ten Brinke, Anneke

    2016-01-01

    Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×109 L−1) were compared with 361 adult-onset asthma patients with low (<0.3×109 L−1) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7–8.1), 3.0 (95% CI 1.1–8.1) and 2.4 (95% CI 1.3–4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice. PMID:27730197

  9. Clinical profile of patients with adult-onset eosinophilic asthma.

    PubMed

    de Groot, Jantina C; Storm, Huib; Amelink, Marijke; de Nijs, Selma B; Eichhorn, Edwin; Reitsma, Bennie H; Bel, Elisabeth H D; Ten Brinke, Anneke

    2016-04-01

    Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×10(9) L(-1)) were compared with 361 adult-onset asthma patients with low (<0.3×10(9) L(-1)) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7-8.1), 3.0 (95% CI 1.1-8.1) and 2.4 (95% CI 1.3-4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice.

  10. Mapping Neurodegenerative Disease Onset and Progression.

    PubMed

    Seeley, William W

    2017-03-13

    Brain networks have been of long-standing interest to neurodegeneration researchers, including but not limited to investigators focusing on conventional prion diseases, which are known to propagate along neural pathways. Tools for human network mapping, however, remained inadequate, limiting our understanding of human brain network architecture and preventing clinical research applications. Until recently, neuropathological studies were the only viable approach to mapping disease onset and progression in humans but required large autopsy cohorts and laborious methods for whole-brain sectioning and staining. Despite important advantages, postmortem studies cannot address in vivo, physiological, or longitudinal questions and have limited potential to explore early-stage disease except for the most common disorders. Emerging in vivo network-based neuroimaging strategies have begun to address these issues, providing data that complement the neuropathological tradition. Overall, findings to date highlight several fundamental principles of neurodegenerative disease anatomy and pathogenesis, as well as some enduring mysteries. These principles and mysteries provide a road map for future research.

  11. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q.

    PubMed Central

    Wirtz, M K; Samples, J R; Kramer, P L; Rust, K; Topinka, J R; Yount, J; Koler, R D; Acott, T S

    1997-01-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. PMID:9012402

  12. Congenital Heart Disease in Adults

    MedlinePlus

    ... and genetics may play a role. Why congenital heart disease resurfaces in adulthood Some adults may find that ... in following adults with congenital heart disease. Congenital heart disease and pregnancy Women with congenital heart disease who ...

  13. Elderly Onset Celiac Disease: A Narrative Review

    PubMed Central

    Cappello, Maria; Morreale, Gaetano C.; Licata, Anna

    2016-01-01

    Celiac sprue is a chronic disease, which usually occurs in children and young adults. However, it can develop in any age group, and the prevalence is increasing even in the elderly population. The atypical patterns of clinical presentation in this age group sometimes can cause a delay in diagnosis. Given the lower sensitivity and specificity of serological tests in the aged population, clinical suspect often arises in the presence of complications (autoimmune disorders, fractures, and finally, malignancy) and must be supported by endoscopic and imaging tools. In this review, we highlight the incidence and prevalence of celiac disease in the elderly, the patterns of clinical presentation, diagnosis, and the most frequent complications, with the aim of increasing awareness and reducing the diagnostic delay of celiac disease even in the elderly population. PMID:27486350

  14. Periocular xanthogranulomas associated with severe adult-onset asthma.

    PubMed Central

    Jakobiec, F A; Mills, M D; Hidayat, A A; Dallow, R L; Townsend, D J; Brinker, E A; Charles, N C

    1993-01-01

    This article describes six patients who presented, usually bilaterally, with yellow-orange, elevated, indurated, and nonulcerated xanthomatous eyelid lesions, typically extending into the anterior orbital fat, and sometimes involving the extraocular muscles and the lacrimal gland. Because the eyelids remained intact and because the process did not reach the deep orbital and perioptic connective tissues, visual acuity was well preserved. There is cosmetic morbidity and occasionally motility restriction with advancing involvement of the extraocular muscles. All patients had variably severe adult-onset asthma that required treatment with systemic prednisone and inhalants. No evidence of Erdheim-Chester disease was found in any patient, but the appearance in one patient, after 25 years of follow-up, of a separate subcutaneous necrobiotic xanthogranulomatous lesion in the mandibular region with an associated paraproteinemia, suggests that at least some of our cases might be a mild form of necrobiotic xanthogranuloma. For this reason, we would suggest repeated periodic serum protein immunoelectrophoretic studies as well as evaluation for lymphoma. Therapy probably should consist of low doses of periorbital radiotherapy coupled with high doses of corticosteroids. Should this not be successful, then systemic administration of corticosteroids with chemotherapeutic agents might be efficacious, as in necrobiotic xanthogranuloma. 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 PMID:8140711

  15. [Adult oligosymptomatic coeliac disease].

    PubMed

    Cabral Rodríguez, R; Arrieta Blanco, F J; Vicente Sánchez, F; Cordobés Martín, F J; Moreno Caballero, B

    2004-12-01

    Coeliac disease is a chronic pathology of the small intestine. The pathogenic mechanism is caused by gluten intolerance. This disease present a characteristic and unspecific injury that causes nutrients and vitamins malabsorption. In adults is an underdiagnosed entity due to atypical forms. To make a premature diagnosis is basic because gluten-free diet prevent the complications after long-term like the intestinal T lymphoma and other digestives malignancies, and decrease the mortality of these patients. We present a case of adult oligosymptomatic coeliac disease in a patient with iron deficiency anaemia and vaginal bleeding. We study the clinic-nutrition and the alterations evolution of the patient.

  16. Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis.

    PubMed

    Santín, Sheila; García-Maset, Rafael; Ruíz, Patricia; Giménez, Isabel; Zamora, Isabel; Peña, Antonia; Madrid, Alvaro; Camacho, Juan A; Fraga, Gloria; Sánchez-Moreno, Ana; Cobo, Maria Angeles; Bernis, Carmen; Ortiz, Alberto; de Pablos, Augusto Luque; Pintos, Guillem; Justa, Maria Luisa; Hidalgo-Barquero, Emilia; Fernández-Llama, Patricia; Ballarín, José; Ars, Elisabet; Torra, Roser

    2009-12-01

    Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as 'severe' or 'mild' using this in silico approach. Our results suggest an earlier onset of the disease in patients with two 'severe' mutations compared to patients with at least one 'mild' mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease.

  17. Right ventricular function in late-onset Pompe disease.

    PubMed

    Fayssoil, Abdallah; Nardi, Olivier; Annane, Djillali; Orlikowski, David

    2014-08-01

    Pompe's disease is a glycogen storage disease (type II) characterized by inherited autosomal recessive transmission. The right ventricular (RV) function is a determinant parameter of clinical outcome in patients with heart failure. We sought to characterize the RV function using Doppler-echocardiography completed by Doppler tissular imaging and tricuspid annular plane systolic excursion (TAPSE) measurement. We analyzed retrospectively clinical and Doppler-echocardiographic data of patients with adult late onset Pompe disease and compared to a control group. Ten patients with late onset Pompe disease were included in our study and were compared to a control group (seven patients). Mean age was 56.7 ± 10.2 years in late onset Pompe disease versus 55 ± 21 years in control group (p  = 0.65). Left ventricular ejection fraction (LVEF) was similar in the two groups (LVEF 63.7 ± 9 vs 63.7 ± 6.6 % in control group p  = 0.99). LV end diastolic diameter was 40.8 ± 6 mm in Pompe disease versus 45.8 ± 6 mm in control group (p  = 0.11). Mean TAPSE was similar in the two groups (25.6 ± 6.2 vs 21.5 ± 2.7 mm p = 0.23). Mean peak systolic RV velocity Sm was not significantly different in the two groups (17.11 ± 3.4 cm/s in Pompe disease vs 16.14 ± 3.8 cm/s in control group p = 0.61). Mean peak early diastolic Ea velocity in the RV were not significantly different in the two groups (15.6 ± 5.6 vs 18.2 ± 4.9 cm/s p = 0.34). According to our data, RV systolic function seems preserved in late-onset Pompe disease.

  18. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Vaccination Recommendations Adult Vaccination Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet ... critical for people with health conditions such as liver disease. If you have chronic liver disease, talk ...

  19. Early onset polycystic kidney disease: how early is early?

    PubMed

    Birewar, Sonali; Zawada, Edward T

    2003-11-01

    We report a case of a six-month-old infant with autosomal dominant polycystic kidney disease. He was a full term baby with an uneventful pre and postnatal period. He was delivered by uncomplicated vaginal delivery without forceps or fetal distress. His father was recently diagnosed with adult onset autosomal dominant polycystic kidney disease (APKD) with creatinine clearance around 25%-30%. The parents requested renal ultrasound of the baby to screen for APKD. It revealed normal sized and normal shaped kidneys, but with multiple bilateral cysts in the renal cortices, each measuring about 5 mm-7 mm in diameter. Subsequent DNA analysis showed presence of PKD1 gene, present on chromosome 16. His renal function was within normal range. The baby needs to be regularly followed-up for the most common complications of APKD, including hypertension and renal insufficiency.

  20. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  1. A novel mouse model that recapitulates adult-onset glycogenosis type 4

    PubMed Central

    Orhan Akman, H.; Emmanuele, Valentina; Kurt, Yasemin Gülcan; Kurt, Bülent; Sheiko, Tatiana; DiMauro, Salvatore; Craigen, William J.

    2015-01-01

    Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen-branching enzyme (GBE). The diagnostic hallmark of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age at onset. Complete loss of enzyme activity is lethal in utero or in infancy and affects primarily the muscle and the liver. However, residual enzyme activity as low as 5–20% leads to juvenile or adult onset of a disorder that primarily affects the central and peripheral nervous system and muscles and in the latter is termed adult polyglucosan body disease (APBD). Here, we describe a mouse model of GSD IV that reflects this spectrum of disease. Homologous recombination was used to knock in the most common GBE1 mutation p.Y329S c.986A > C found in APBD patients of Ashkenazi Jewish decent. Mice homozygous for this allele (Gbe1ys/ys) exhibit a phenotype similar to APBD, with widespread accumulation of PG. Adult mice exhibit progressive neuromuscular dysfunction and die prematurely. While the onset of symptoms is limited to adult mice, PG accumulates in tissues of newborn mice but is initially absent from the cerebral cortex and heart muscle. Thus, PG is well tolerated in most tissues, but the eventual accumulation in neurons and their axons causes neuropathy that leads to hind limb spasticity and premature death. This mouse model mimics the pathology and pathophysiologic features of human adult-onset branching enzyme deficiency. PMID:26385640

  2. Operational Thought in Alzheimer's Disease Early Onset and SDAT.

    ERIC Educational Resources Information Center

    Emery, Olga B.; Breslau, Lawrence D.

    For more than a decade it has been convention to assume that senile dementia Alzheimer's type (SDAT) and Alzheimer's disease early onset represent a unitary disease process with only an onset difference. This assumption has been neither confirmed nor disconfirmed. To address this issue, a study was conducted which analyzed the dissolution of…

  3. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

    SciTech Connect

    Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

    1997-02-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57 refs., 3 figs., 3 tabs.

  4. Renal Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  5. Coeliac disease in adults.

    PubMed

    Corazza, G R; Gasbarrini, G

    1995-06-01

    Coeliac disease is a chronic disease characterized by small bowel villous atrophy which impairs nutrient absorption and improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. Knowledge of the adult form of coeliac disease has greatly improved in recent years. Although this knowledge is not yet sufficiently widespread among referring clinicians, it has, over the past few years, allowed an increasing number of patients to be diagnosed with subclinical forms characterized by minor, transient or apparently unrelated symptoms. As a consequence, our views on the clinical and epidemiological aspects of this condition, the prevalence of which in the general population is believed to be close to 1 in 300, have changed and are still changing. Since it has been demonstrated that a strict gluten-free diet is protective against the complications of adult coeliac disease, it is important that even subclinical and silent forms are diagnosed and treated as early as possible. Non-invasive screening tests, such as anti-gliadin and anti-endomysium antibody estimation, should therefore be used systematically in groups considered to be at risk of coeliac disease. These include first-degree relatives of coeliac patients and patients with insulin-dependent diabetes mellitus, iron-deficiency anaemia, epilepsy with cerebral calcification, recurrent aphthous stomatitis and dental enamel hypoplasia. Other conditions will probably be identified in the near future.

  6. Guinea worm cause of adult onset asthmatic attack, a radiological diagnosis.

    PubMed

    Marchie, T T

    1999-01-01

    A case report of a fifty years old Hausa male from Sokoto town, Nigeria an endemic region of guinea worm infestation, who presented with sudden adult onset of asthmatic attack and was evaluated radiologically and the diagnosis of acute obstructive airway disease was confirmed. It was noted, that there were associated calcified chain of guinea worms in the lung parenchyma. A rare association of acute asthmatic attack. Patient responded there-after to an anti-asthmatic regime of management.

  7. Age-at-Onset in Late Onset Alzheimer Disease is Modified by Multiple Genetic Loci

    PubMed Central

    Naj, Adam C.; Jun, Gyungah; Reitz, Christiane; Kunkle, Brian W.; Perry, William; Park, YoSon; Beecham, Gary W.; Rajbhandary, Ruchita A.; Hamilton-Nelson, Kara L.; Wang, Li-San; Kauwe, John S.K.; Huentelman, Matthew J.; Myers, Amanda J.; Bird, Thomas D.; Boeve, Bradley F.; Baldwin, Clinton T.; Jarvik, Gail P.; Crane, Paul K.; Rogaeva, Ekaterina; Barmada, Michael M.; Demirci, F. Yesim; Cruchaga, Carlos; Kramer, Patricia; Ertekin-Taner, Nilufer; Hardy, John; Graff-Radford, Neill R.; Green, Robert C.; Larson, Eric B.; St George-Hyslop, Peter; Buxbaum, Joseph D.; Evans, Denis; Schneider, Julie A.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Saykin, Andrew J.; Reiman, Eric M.; De Jager, Philip L.; Bennett, David A.; Morris, John C.; Montine, Thomas J.; Goate, Alison M.; Blacker, Deborah; Tsuang, Debby W.; Hakonarson, Hakon; Kukull, Walter A.; Foroud, Tatiana M.; Martin, Eden R.; Haines, Jonathan L.; Mayeux, Richard; Farrer, Lindsay A.; Schellenberg, Gerard D.; Pericak-Vance, Margaret A.

    2015-01-01

    Importance As APOE locus variants contribute to both risk of late-onset Alzheimer disease and differences in age-at-onset, it is important to know if other established late-onset Alzheimer disease risk loci also affect age-at-onset in cases. Objectives To investigate the effects of known Alzheimer disease risk loci in modifying age-at-onset, and to estimate their cumulative effect on age-at-onset variation, using data from genome-wide association studies in the Alzheimer’s Disease Genetics Consortium (ADGC). Design, Setting and Participants The ADGC comprises 14 case-control, prospective, and family-based datasets with data on 9,162 Caucasian participants with Alzheimer’s occurring after age 60 who also had complete age-at-onset information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single nucleotide polymorphisms (SNPs) most significantly associated with risk at ten confirmed LOAD loci were examined in linear modeling of AAO, and individual dataset results were combined using a random effects, inverse variance-weighted meta-analysis approach to determine if they contribute to variation in age-at-onset. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. Main Outcomes and Measures Age at disease onset abstracted from medical records among participants with late-onset Alzheimer disease diagnosed per standard criteria. Results Analysis confirmed association of APOE with age-at-onset (rs6857, P=3.30×10−96), with associations in CR1 (rs6701713, P=7.17×10−4), BIN1 (rs7561528, P=4.78×10−4), and PICALM (rs561655, P=2.23×10−3) reaching statistical significance (P<0.005). Risk alleles individually reduced age-at-onset by 3-6 months. Burden analyses demonstrated that APOE contributes to 3.9% of variation in age-at-onset (R2=0.220) over baseline (R2=0.189) whereas the other nine loci together contribute to 1.1% of

  8. Similarity of HLA-DQ profiles in adult-onset type 1 insulin-dependent diabetic patients with and without extra-pancreatic auto-immune disease.

    PubMed

    Gu, X F; Larger, E; Clauser, E; Assan, R

    1992-01-01

    Some insulin-dependent diabetic patients present with auto-immune diseases involving extra pancreatic tissues (type 1b diabetes mellitus). The genetic specificity of this syndrome, as opposed to insulin dependent diabetes mellitus (IDDM) free of such associations (Type 1a IDDM) is not clearly established. We have analyzed the HLA-DQB1 and DQA1, loci, after PCR amplification of genomic DNA, in 44 Type 1b IDDM patients, 78 Type 1a IDDM patients and 105 control subjects. No essential difference in HLA-DQ profiles appeared between Type 1b and Type 1a IDDM patients. Both diabetic groups displayed a significant enrichment in DQB1 alleles negative for aspartate at position 57 (Type 1b: 83%; Type 1a: 89%; controls 48%; p < 0.001 vs both patient groups) and in DQB1 Asp 57 negative homozygosity: 71% of Type 1b; 80% of Type 1a; 25% of controls (p < 0.01). This enrichment in DQB1 Asp 57 negative alleles was accounted for by DQB1* 0201 in the Type 1b group, and by DQB1 % 0201 and 0302 in the Type 1a patients. Conversely, alleles DQB1* 0602 and 0301 (DQB1 Asp 57 positive) were protective. Both diabetic groups also displayed a significant enrichment in DQA1 alleles positives for arginine at position 52 (65% of Type 1b; 76% of Type 1a; 50% of control subjects; p < 0.01 and 0.001, respectively, vs controls), and in DQA1 Arg 52 positive homozygotes (48% of Type 1b, 58% of Type 1a, 22% of control subjects; p < 0.01). All differences between diabetic groups and the control group were more pronounced in the case of Type 1a than of Type 1b patients. The HLA-DQ genes shared by Type 1a and Type 1b patients must therefore be closely associated with islet autoimmunity. Genetic differences between Type 1a and Type 1b syndromes, if any, must be investigated in other MHC and non-MHC regions of the genome.

  9. Chromosome 14 and late-onset familial alzheimer disease (FAD)

    SciTech Connect

    Schellenberg, G.D.; Anderson, L.; Nemens, E.; Bird, T.D.; Wijsman, E.M.; Martin, G.M.; Payami, H.; Orr, H.T.; White, J.A.; Alonso, M.E.

    1993-09-01

    Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analysis were used, in 49 families with a mean age at onset [>=]60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score [>=]2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P<.02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset [>=]60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. 37 refs., 1 fig., 6 tabs.

  10. Chromosome 14 and late-onset familial Alzheimer disease (FAD)

    PubMed Central

    Schellenberg, Gerard D.; Payami, Haydeh; Wijsman, Ellen M.; Orr, Harry T.; Goddard, Katrina A. B.; Anderson, Leojean; Nemens, Ellen; White, June A.; Alonso, M. Elisa; Ball, Melvyn J.; Kaye, Jeffrey; Morris, John C.; Chui, Helena; Sadovnick, A. Dessa; Heston, Leonard L.; Martin, George M.; Bird, Thomas D.

    1993-01-01

    Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analyses were used, in 49 families with a mean age at onset ≥60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score ≤ –2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P < .02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset ≥60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. PMID:8352272

  11. Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

    PubMed

    Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil

    2016-09-01

    OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database.

  12. Factors related to onset age of Huntington disease.

    PubMed Central

    Myers, R H; Madden, J J; Teague, J L; Falek, A

    1982-01-01

    One prominent feature of Huntington disease (HD) is the variable age at which the characteristic neurological or psychiatric symptoms appear. Ages of manifestation varying from 4 to 65 years are found in a sample of 95 HD pedigrees compiled since 1968 from the Southeastern United States. Significant parent-child correlations of age of onset indicate consistency of onset age within nuclear families. However, an average intrafamily range of 9 years and an average intrapedigree range of 12 years reveal substantial variability of onset age within these groups. Of the nine cases of juvenile-onset HD identified in this sample, seven were of paternal descent. The preponderance of juvenile patients inheriting the HD gene from a father confirms similar findings from other studies. In addition, a trend toward earlier onset in all offspring of paternal transmission suggests that the juvenile-onset phenomenon is only the tail of a shift in the curve of onset ages for this group. A trend toward earlier onset in successive generations was noted. This "anticipation" may reflect the finding that persons of early onset in prior generations are selectively nonreproductive as a result of manifestation of the disorder. By identifying familial factors influencing onset age of HD, it may be possible to more effectively evaluate environmental factors that influence the onset of the disorder. PMID:6211092

  13. Association studies in late onset sporadic Alzheimer`s disease

    SciTech Connect

    Goate, A.M.; Lendon, C.; Talbot, C.

    1994-09-01

    Alzheimer`s disease (AD) is characterized by an adult onset progressive dementia and the presence of numerous plaques and tangles within the brain at autopsy. The senile plaques are composed of a proteinaceous core surrounded by dystrophic neurites. The major protein component of the core is {beta}-amyloid but antibodies to many other proteins bind to senile plaques, e.g., antibodies to apolioprotein E (ApoE) and to {alpha}1-antichymotrypsin (AACT). Genetic studies have implicated mutations within the {beta}-amyloid precursor protein gene as the cause of AD in a small number of early onset AD families. More recently, assocition studies in late onset AD have demonstrated a positive association between ApoE-{epsilon}4 and AD. We report evidence for a negative association between ApoE-{epsilon}2 and AD in a large sample of sporadic late onset AD cases and matched controls supporting the role of ApoE in the etiology of AD. Ninety-three patients with sporadic AD (average age = 75 years, s.d. 8 yrs.) and 67 normal controls from the same ethnic background (age = 77 yrs., s.d. 10 yrs.) were recruited through the patient registry of the Washington University Alzheimer`s Disease Research Center. We found a statistically significant increase in ApoE-{epsilon}4 allele frequency in patients compared with controls ({chi}{sup 2}=7.75, 1 d.f., one tailed p=0.0027) and a significant decrease in {epsilon}2 allele frequency (Fisher`s exact test, one tailed p=0.0048), whereas the decreased frequency of {epsilon}3 in the patient groups was not statistically significant. Allele {epsilon}2 conferred a strong protective effect in our sample, with the odds ratio for AD for subjects possessing this allele being 0.08 (85% confidence interval 0.01-0.69). Similar studies using a polymorphism within the AACT gene showed no association with alleles at this locus in the entire AD sample or in AD cases homozygous for ApoE-{epsilon}3.

  14. Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease

    PubMed Central

    Kikah, Ngum; Ekokobe, Fonkem; Atem, Folefac D.

    2016-01-01

    Objective The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD (with a threshold at age 55 years for a male or 65 years for a female). However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD. Methods We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn’t experience onset of CVD) and Cox proportional regression analysis, with offspring’s age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD. Results Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD (P < .0001; N = 1401) and for paternal age of onset of CVD (P = 0.0134; N = 1221). A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders. Conclusions Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of

  15. Effects of diabetes mellitus on bone mass in juvenile and adult-onset diabetes.

    PubMed

    Levin, M E; Boisseau, V C; Avioli, L V

    1976-01-29

    To assess the influence of diabetes mellitus on bone metabolism, we measured skeletal mass in the forearms of 35 patients with juvenile diabetes on insulin and 101 stable patients with adult-onset diabetes, on diet alone, insulin, or oral hypoglycemic agents. There was a significant loss of bone mass in both juvenile and adult-onset diabetes (P less than 0.01) as compared to controls matched for age and sex. The decrease was already present in patients with diabetes of less than five years' duration. Bone loss and duration of the diabetes did not correlate; the greatest decrease in bone mass was observed in the patients receiving oral agents. These data are consistent with the hypothesis that the loss of skeletal tissue in diabetes reflects the underlying disease since it occurs early and is not related to severity as evidenced by the need for insulin, to duration, or to treatment with insulin or diet alone.

  16. Interstitial lung disease - adults - discharge

    MedlinePlus

    ... lung disease Pulmonary alveolar proteinosis Rheumatoid lung disease Sarcoidosis Patient Instructions Eating extra calories when sick - adults ... team. Related MedlinePlus Health Topics Interstitial Lung Diseases Sarcoidosis Browse the Encyclopedia A.D.A.M., Inc. ...

  17. Late-onset Tay-Sachs disease: adverse effects of medications and implications for treatment.

    PubMed

    Shapiro, B E; Hatters-Friedman, S; Fernandes-Filho, J A; Anthony, K; Natowicz, M R

    2006-09-12

    The authors conducted a retrospective and brief prospective study of adverse effects of approximately 350 medications in 44 adults with late-onset Tay-Sachs disease (LOTS). Some medications were relatively safe, whereas others, particularly haloperidol, risperidone, and chlorpromazine, were associated with neurologic worsening.

  18. Screening for late-onset Pompe disease in Finland.

    PubMed

    Palmio, Johanna; Auranen, Mari; Kiuru-Enari, Sari; Löfberg, Mervi; Bodamer, Olaf; Udd, Bjarne

    2014-11-01

    Pompe disease (glycogen storage disease type II) is caused by autosomal recessive mutations in GAA gene. The estimated frequency of late-onset Pompe disease is around 1:60,000. However, only two infantile and one late-onset Pompe patients have been reported in Finland with a population of 5 million. We screened for late-onset Pompe disease in a cohort of undetermined myopathy patients with proximal muscle weakness and/or elevated serum creatine kinase values. Acid α-glucosidase (GAA) activity in dried blood spots was measured and clinical data collected in 108 patients. Four patients had low normal GAA activity; all the others had activities well within the normal range. Re-analyses of these patients did not reveal new Pompe patients. Our findings suggest that Pompe disease is extremely rare in Finland. Finland is an example of an isolated population with enrichment of certain mutations for genetic disorders and low occurrence of some autosomal recessive diseases.

  19. CONSENSUS TREATMENT RECOMMENDATIONS FOR LATE-ONSET POMPE DISEASE

    PubMed Central

    Cupler, Edward J.; Berger, Kenneth I.; Leshner, Robert T.; Wolfe, Gil I.; Han, Jay J.; Barohn, Richard J.; Kissel, John T.

    2012-01-01

    Introduction Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase. Late-onset Pompe disease is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders. Methods Objective is to propose consensus-based treatment and management recommendations for late-onset Pompe disease. Methods A systematic review of the literature by a panel of specialists with expertise in Pompe disease was undertaken. Conclusions A multidisciplinary team should be involved to properly treat the pulmonary, neuromuscular, orthopedic, and gastrointestinal elements of late-onset Pompe disease. Presymptomatic patients with subtle objective signs of Pompe disease (and patients symptomatic at diagnosis) should begin treatment with enzyme replacement therapy (ERT) immediately; presymptomatic patients without symptoms or signs should be observed without use of ERT. After 1 year of ERT, patients’ condition should be reevaluated to determine whether ERT should be continued. PMID:22173792

  20. Distinguishing adult-onset asthma from COPD: a review and a new approach

    PubMed Central

    Abramson, Michael J; Perret, Jennifer L; Dharmage, Shyamali C; McDonald, Vanessa M; McDonald, Christine F

    2014-01-01

    Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene–environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and

  1. Slow saccades in bulbar-onset motor neurone disease.

    PubMed

    Donaghy, Colette; Pinnock, Ralph; Abrahams, Sharon; Cardwell, Chris; Hardiman, Orla; Patterson, Victor; McGivern, R Canice; Gibson, J Mark

    2010-07-01

    Historical studies of eye movements in motor neurone disease (MND) have been conflicting although current findings suggest that eye movement abnormalities relate to frontal lobe impairment. Numerous case reports, however, describe slow saccades and supranuclear gaze palsies in patients with MND often associated with bulbar-onset disease. We performed a study of saccades and smooth pursuit in a large group of patients with MND to examine for any differences between bulbar-onset and spinal-onset patients. Forty-four patients (14 bulbar-onset and 30 spinal-onset patients) and 45 controls were recruited. Reflexive saccades, antisaccades and smooth pursuit were examined using infra-red oculography and all subjects then underwent neuropsychological evaluation. Reflexive saccades were found to be slower in bulbar-onset compared to spinal-onset patients and controls (p = 0.03, p = 0.05). Antisaccade latency (p = 0.01) and antisaccade type 1 errors (p = 0.03, p = 0.04) were increased in patients compared to controls. 'Proportion of time spent in smooth pursuit' and smooth pursuit 'velocity gain' were reduced in patients compared to controls (p = 0.000, p = 0.001). Antisaccade errors and velocity gain correlated with neuropsychological measures sensitive to lesions of the frontal lobes. This is the first study to highlight the presence of slow saccades in bulbar-onset MND. These findings suggest that slow saccades may be due to increased brainstem pathology in bulbar-onset disease that involves burst cell neurons. Furthermore these observations highlight the potential for overlap between bulbar-onset MND and progressive supranuclear palsy (PSP) as both can have a bulbar palsy and slowed saccades.

  2. Juvenile versus adult-onset ankylosing spondylitis -- clinical, radiographic, and social outcomes. a systematic review.

    PubMed

    Jadon, Deepak R; Ramanan, Athimalaipet V; Sengupta, Raj

    2013-11-01

    Ankylosing spondylitis (AS) has 2 main modes of onset: juvenile-onset AS (JoAS) and adult-onset AS (AoAS). It is not known whether JoAS is a subtype of AS, or AS modulated by early age of onset and longer disease duration. We performed a systematic review of the literature, identifying 12 articles and 1 abstract directly comparing JoAS and AoAS cohorts, with observational study design. Patients with JoAS appear to have more peripheral joint involvement both clinically and radiographically (especially knees and ankles) and more root joint involvement (hips and shoulders); they are more likely to proceed to hip arthroplasty and often initially present with peripheral rather than axial symptoms. Patients with AoAS appear to have more axial symptoms and radiographic disease, particularly in the lumbar spine, and worse axial metrology. In terms of other characteristics, more evidence is needed to confidently state whether JoAS and AoAS are different.

  3. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2014-04-01

    Mayeux RP, Alzheimer’s Disease Genetics Consortium. Whole-exome sequencing of Hispanic early-onset Alzheimer disease families identifies rare variants...majority of genetic risk for this form of Alzheimer disease unexplained. We performed Whole-Exome Sequencing (WES) on 55 individuals in 19 Caribbean...EOAD and ~11% of EOAD overall, leaving the majority of genetic risk for the most severe form of Alzheimer disease unexplained. Methods We

  4. [Clinical guidelines for infantile-onset Pompe disease].

    PubMed

    Pascual-Pascual, S I; Nascimento, A; Fernandez-Llamazares, C M; Medrano-Lopez, C; Villalobos-Pinto, E; Martinez-Moreno, M; Ley, M; Manrique-Rodriguez, S; Blasco-Alonso, J

    2016-09-16

    Infantile-onset Pompe disease has a fatal prognosis in the short term unless it is diagnosed at an early stage and enzyme replacement therapy is not started as soon as possible. A group of specialists from different disciplines involved in this disease have reviewed the current scientific evidence and have drawn up an agreed series of recommendations on the diagnosis, treatment and follow-up of patients. We recommend establishing enzyme treatment in any patient with symptomatic Pompe disease with onset within the first year of life, with a clinical and enzymatic diagnosis, and once the CRIM (cross-reactive immunological material) status is known.

  5. Clustering of (auto)immune diseases with early-onset and complicated inflammatory bowel disease.

    PubMed

    Bueno de Mesquita, Mirjam; Ferrante, Marc; Henckaerts, Liesbet; Joossens, Marie; Janssens, Virginie; Hlavaty, Tibor; Pierik, Marie; Joossens, Sofie; Van Schuerbeek, Nele; Van Assche, Gert; Rutgeerts, Paul; Vermeire, Severine; Hoffman, Ilse

    2009-05-01

    Studies in adult inflammatory bowel disease (IBD) patients have highlighted associations with genetic and serologic markers and suggest an association with disease location, behaviour and natural history. Data on patients with Crohn's disease (CD, n=80), ulcerative colitis (UC, n=15) and indeterminate colitis (n=4) were collected. All individuals were analysed for CARD15 R702W, G908R and L1007fs for toll-like receptor 4 (TLR4) Asp299Gly and for anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmatic antibodies (pANCA). After a mean of 10.7 years of follow up, the disease behaviour changed in 45% of CD patients, in contrast to disease location, where only 12.5% had a change (p<0.001). The younger the age at diagnosis, the more patients presented with colonic disease (p=0.021). Also, more TLR4 Asp299 Gly variants were found when the age at onset was younger (p=0.018). A large number of concomitant diseases were observed. There was no difference in the prevalence of TLR4 variants nor ASCA or pANCA between the patients with or without concomitant diseases. Patients who progressed more often needed surgery as compared to patients who remained free of stenosing or fistulising disease (27/32 or 84% versus 3/35 or 8.6%, respectively, p<0.0001) and more often had concomitant immune-mediated diseases and a trend for more seroreactivity towards ASCA.

  6. Childhood adversities and adult-onset asthma: a cohort study

    PubMed Central

    Korkeila, Jyrki; Lietzen, Raija; Sillanmäki, Lauri H; Rautava, Päivi; Korkeila, Katariina; Kivimäki, Mika; Koskenvuo, Markku; Vahtera, Jussi

    2012-01-01

    Objectives Childhood adversities may be important determinants of later illnesses and poor health behaviour. However, large-scale prospective studies on the associations between childhood adversities and the onset of asthma in adulthood are lacking. Design Prospective cohort study with 7-year follow-up. Setting Nationally representative study. Data were collected from the Health and Social Support (HeSSup) survey and national registers. Participants The participants represent the Finnish population from the following age groups: 20–24, 30–34, 40–44, and 50–54 years at baseline in 1998 (24 057 survey participants formed the final cohort of this study). The occurrence of childhood adversities was assessed at baseline with a six-item survey scale. The analyses were adjusted for sociodemographic characteristics, behavioural health risks and common mental disorders. Primary and secondary outcomes The survey data were linked to data from national health registers on incident asthma during a 7-year follow-up to define new-onset asthma cases with verified diagnoses. Results A total of 12 126 (59%) participants reported that they encountered a childhood adversity. Of them 3677 (18% of all) endured three to six adversities. During a follow-up of 7 years, 593 (2.9%) participants were diagnosed with incident asthma. Those who reported three or more childhood adversities had a 1.6-fold (95% CI 1.31 to 2.01) greater risk of asthma compared to those without childhood adversities. This hazard attenuated but remained statistically significant after adjustment for conventional risk factors (HR 1.33; 95% CI 1.06 to 1.67). Conclusions Adults who report having encountered adversities in childhood may have an increased risk of developing asthma. PMID:23069774

  7. Predictive Medicine: Recombinant DNA Technology and Adult-Onset Genetic Disorders

    PubMed Central

    Hayden, Michael

    1988-01-01

    Genetic factors are of great importance in common adult-onset disorders such as atherosclerosis, cancer, and neuro-degenerative diseases. Advances in DNA technology now allow identification of persons at high-risk of developing some of these diseases. This advance is leading to predictive medicine. In some genetic disorders, such as those leading to atherosclerosis and cancer, identification of high-risk individuals allows intervention which alters the natural history of the disorder. In other diseases, for which there is no treatment, such as Huntington's disease, the application of this technology provides information that relieves uncertainty and may affect quality of life, but does not alter the course of the illness. General implementation of predictive testing programs awaits the results of pilot projects, which will demonstrate the needs, appropriate levels of support, and guidelines for delivery of such testing. PMID:21253100

  8. Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

    ERIC Educational Resources Information Center

    de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.

    2007-01-01

    This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

  9. Late-onset adenosine deaminase deficiency presenting with Heck's disease.

    PubMed

    Artac, Hasibe; Göktürk, Bahar; Bozdemir, Sefika Elmas; Toy, Hatice; van der Burg, Mirjam; Santisteban, Ines; Hershfield, Michael; Reisli, Ismail

    2010-08-01

    Focal epithelial hyperplasia, also known as Heck's disease, is a rare but distinctive entity of viral etiology with characteristic clinical and histopathological features. It is a benign, asymptomatic disease of the oral mucosa caused by human papilloma viruses (HPV). Previous studies postulated an association between these lesions and immunodeficiency. Genetic deficiency of adenosine deaminase (ADA) results in varying degrees of immunodeficiency, including neonatal onset severe combined immunodeficiency (ADA-SCID), and milder, later onset immunodeficiency. We report a 12-year-old girl with the late onset-ADA deficiency presenting with Heck's disease. Our case report should draw attention to the possibility of immunodeficiency in patients with HPV-induced focal epithelial hyperplasia.

  10. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2013-04-01

    is genetically associated with Alzheimer disease. Nat Genet 2007;39(2):168-177. 33. McKhann G, Drachman D, Folstein M. Clinical diagnosis of...13. SUPPLEMENTARY NOTES 14. ABSTRACT The primary focus toward identification of Alzheimer disease (AD) risk genes over the past five years has...been testing the common disease common variant (CDCV) hypothesis through the use of genome-wide association studies (GWAS) in late onset Alzheimer

  11. Early-onset Hirayama disease in a female

    PubMed Central

    Baumann, Matthias; Finsterer, Josef; Gizewski, Elke R; Löscher, Wolfgang N

    2017-01-01

    Objectives: Hirayama disease is a rare myelopathy, occurring predominantly in males with onset in the teens. Methods and results: Here, we report a young female patient who developed the first signs of Hirayama disease at 10.5 years of age. Prior to onset, she had experienced a growth spurt and grew about 8 cm. The disease progressed over 3 years and the typical clinical, electrophysiological, and neuroimaging signs of Hirayama disease were found. After this period and achievement of her final height, no further progression was noticed. Conclusions: This case highlights that pediatric neurologists should be aware of Hirayama disease, which can also occur in girls in early adolescence. PMID:28228960

  12. Pediatric-Onset and Adult-Onset Separation Anxiety Disorder Across Countries in the World Mental Health Survey

    PubMed Central

    Silove, Derrick; Alonso, Jordi; Bromet, Evelyn; Gruber, Mike; Sampson, Nancy; Scott, Kate; Andrade, Laura; Benjet, Corina; de Almeida, Jose Miguel Caldas; De Girolamo, Giovanni; de Jonge, Peter; Demyttenaere, Koen; Fiestas, Fabian; Florescu, Silvia; Gureje, Oye; He, Yanling; Karam, Elie; Lepine, Jean-Pierre; Murphy, Sam; Villa-Posada, Jose; Zarkov, Zahari; Kessler, Ronald C.

    2016-01-01

    Objective The age-at-onset criterion for separation anxiety disorder was removed in DSM-5, making it timely to examine the epidemiology of separation anxiety disorder as a disorder with onsets spanning the life course, using cross-country data. Method The sample included 38,993 adults in 18 countries in the World Health Organization (WHO) World Mental Health Surveys. The WHO Composite International Diagnostic Interview was used to assess a range of DSM-IV disorders that included an expanded definition of separation anxiety disorder allowing onsets in adulthood. Analyses focused on prevalence, age at onset, comorbidity, predictors of onset and persistence, and separation anxiety-related role impairment. Results Lifetime separation anxiety disorder prevalence averaged 4.8% across countries (interquartile range [25th–75th percentiles]=1.4%–6.4%), with 43.1% of lifetime onsets occurring after age 18. Significant time-lagged associations were found between earlier separation anxiety disorder and subsequent onset of internalizing and externalizing DSM-IV disorders and conversely between these disorders and subsequent onset of separation anxiety disorder. Other consistently significant predictors of lifetime separation anxiety disorder included female gender, retrospectively reported childhood adversities, and lifetime traumatic events. These predictors were largely comparable for separation anxiety disorder onsets in childhood, adolescence, and adulthood and across country income groups. Twelve-month separation anxiety disorder prevalence was considerably lower than lifetime prevalence (1.0% of the total sample; interquartile range=0.2%–1.2%). Severe separation anxiety-related 12-month role impairment was significantly more common in the presence (42.4%) than absence (18.3%) of 12-month comorbidity. Conclusions Separation anxiety disorder is a common and highly comorbid disorder that can have onset across the lifespan. Childhood adversity and lifetime trauma are

  13. Genetic testing of children for diseases that have onset in adulthood: the limits of family interests.

    PubMed

    Hardart, George E; Chung, Wendy K

    2014-10-01

    Two recent policy statements, one from the American Academy of Pediatrics and one from the American College of Medical Genetics, reach very different conclusions about the question of whether children should be tested for adult-onset genetic conditions. The American Academy of Pediatrics policy begins with the presumption that genetic testing for children should be driven by the best interest of the child. It recognizes the importance of preserving the child's open future, recommending that genetic testing for adult-onset diseases be deferred. The American College of Medical Genetics, by contrast, recommended testing children for at least some adult conditions, although it should be noted they have recently modified this recommendation. They justified this recommendation by arguing that it, in fact, was in the best interests of the child and family to receive this information. In this article, we analyze these 2 different positions and suggest ways that the seeming conflicts between them might be reconciled.

  14. Voice Onset Time Production in Speakers with Alzheimer's Disease

    ERIC Educational Resources Information Center

    Baker, Julie; Ryalls, Jack; Brice, Alejandro; Whiteside, Janet

    2007-01-01

    In the present study, voice onset time (VOT) measurements were compared between a group of individuals with moderate Alzheimer's disease (AD) and a group of healthy age- and gender-matched peers. Participants read a list of consonant-vowel-consonant (CVC) words, which included the six stop consonants. The VOT measurements were made from…

  15. Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and FTD

    PubMed Central

    van der Zee, Julie; Mariën, Peter; Crols, Roeland; Van Mossevelde, Sara; Dillen, Lubina; Perrone, Federica; Engelborghs, Sebastiaan; Verhoeven, Jo; D'aes, Tine; Ceuterick-De Groote, Chantal; Sieben, Anne; Versijpt, Jan; Cras, Patrick; Martin, Jean-Jacques

    2016-01-01

    Objective: To investigate the molecular basis of a Belgian family with autosomal recessive adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease [KD]) with pronounced frontal lobe involvement and to expand the findings to a cohort of unrelated Belgian patients with frontotemporal dementia (FTD). Methods: Genetic screening in the ANCL family and FTD cohort (n = 461) was performed using exome sequencing and targeted massive parallel resequencing. Results: We identified a homozygous mutation (p.Ile404Thr) in the Cathepsin F (CTSF) gene cosegregating in the ANCL family. No other mutations were found that could explain the disease in this family. All 4 affected sibs developed motor symptoms and early-onset dementia with prominent frontal features. Two of them evolved to akinetic mutism. Disease presentation showed marked phenotypic variation with the onset ranging from 26 to 50 years. Myoclonic epilepsy in one of the sibs was suggestive for KD type A, while epilepsy was not present in the other sibs who presented with clinical features of KD type B. In a Belgian cohort of unrelated patients with FTD, the same heterozygous p.Arg245His mutation was identified in 2 patients who shared a common haplotype. Conclusions: A homozygous CTSF mutation was identified in a recessive ANCL pedigree. In contrast to the previous associations of CTSF with KD type B, our findings suggest that CTSF genetic testing should also be considered in patients with KD type A as well as in early-onset dementia with prominent frontal lobe and motor symptoms. PMID:27668283

  16. Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis

    PubMed Central

    Yang, Yi; Lynch, David R.; Lukas, Thomas; Ahmeti, Kreshnik; Sleiman, Patrick M.A.; Ryan, Eanna; Schadt, Kimberly A.; Newman, Jordan H.; Deng, Han-Xiang; Siddique, Nailah

    2016-01-01

    Objective: To identify the genetic defect for adult-onset primary lateral sclerosis (PLS) in a family with 5 patients. Methods: Whole-exome sequencing was performed to identify the shared genetic variants in 3 affected members in a PLS family with 5 affected individuals. Sanger sequencing was used for validation of the variants and for cosegregation analysis. Mitochondrial activity for both patients and unaffected siblings was measured using a SeaHorse metabolic analyzer. Results: Whole-exome sequencing and subsequent cosegregation analysis demonstrated that compound heterozygous missense variants L695P and I743T in SPG7 were the only mutations cosegregating with the disease in an autosomal recessive fashion in this family. The parents and siblings are genetically heterozygous and clinically unaffected. Functional studies suggested that the PLS-associated SPG7 mutants affect mitochondrial function when glucose is reduced. Conclusions: Compound heterozygote mutations in SPG7 are associated with adult-onset PLS, extending the spectrum of SPG7-linked neurologic diseases. Patients with the PLS phenotype should have genetic testing for paraplegin, especially when the condition is familial. PMID:27123479

  17. Genetic diseases in adults.

    PubMed

    Kolettis, Peter N

    2003-02-01

    Genetic diseases that do not primarily affect the genitourinary tract may have urologic manifestations. These urologic manifestations range from benign and malignant renal disease to infertility. Thus, the practicing urologist may be involved in the care of these patients and should have knowledge of these diseases. Continued improvements in the diagnosis and treatment of these genetic diseases will likely result in improved survival and will increase the number of patients who may develop urologic manifestations of these diseases.

  18. A common genetic background could explain early-onset Crohn's disease.

    PubMed

    Bianco, Anna Monica; Zanin, Valentina; Girardelli, Martina; Magnolato, Andrea; Martelossi, Stefano; Martellossi, Stefano; Tommasini, Alberto; Marcuzzi, Annalisa; Crovella, Sergio

    2012-04-01

    Crohn's disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn's disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.

  19. Glucose Metabolic Brain Networks in Early-Onset vs. Late-Onset Alzheimer's Disease

    PubMed Central

    Chung, Jinyong; Yoo, Kwangsun; Kim, Eunjoo; Na, Duk L.; Jeong, Yong

    2016-01-01

    Objective: Early-onset Alzheimer's disease (EAD) shows distinct features from late-onset Alzheimer's disease (LAD). To explore the characteristics of EAD, clinical, neuropsychological, and functional imaging studies have been conducted. However, differences between EAD and LAD are not clear, especially in terms of brain connectivity and networks. In this study, we investigated the differences in metabolic connectivity between EAD and LAD by adopting graph theory measures. Methods: We analyzed 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images to investigate the distinct features of metabolic connectivity between EAD and LAD. Using metabolic connectivity and graph theory analysis, metabolic network differences between LAD and EAD were explored. Results: Results showed the decreased connectivity centered in the cingulate gyri and occipital regions in EAD, whereas decreased connectivity in the occipital and temporal regions as well as increased connectivity in the supplementary motor area were observed in LAD when compared with age-matched control groups. Global efficiency and clustering coefficients were decreased in EAD but not in LAD. EAD showed progressive network deterioration as a function of disease severity and clinical dementia rating (CDR) scores, mainly in terms of connectivity between the cingulate gyri and occipital regions. Global efficiency and clustering coefficients were also decreased along with disease severity. Conclusion: These results indicate that EAD and LAD have distinguished features in terms of metabolic connectivity, with EAD demonstrating more extensive and progressive deterioration. PMID:27445800

  20. Latin America: native populations affected by early onset periodontal disease.

    PubMed

    Nowzari, Hessam; Botero, Javier Enrique

    2011-06-01

    Millions of individuals are affected by early onset periodontal disease in Latin America, a continent that includes more than 20 countries. The decision-makers claim that the disease is not commonly encountered. In 2009, 280,919 authorized immigrants were registered in the United States versus 5,460,000 unauthorized (2,600,000 in California). The objective of the present article is to raise awareness about the high prevalence of the disease among Latin Americans and the good prognosis of preventive measures associated with minimal financial cost.

  1. Genetics Home Reference: adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

    MedlinePlus

    ... it causes a severe decline in thinking and reasoning abilities (dementia). Over time, motor skills are affected, ... Schmahmann JD. Adult onset leukodystrophy with neuroaxonal spheroids: clinical, neuroimaging and neuropathologic observations. Brain Pathol. 2009 Jan; ...

  2. The onset of nonmotor symptoms in Parkinson's disease (the ONSET PD study).

    PubMed

    Pont-Sunyer, Claustre; Hotter, Anna; Gaig, Carles; Seppi, Klaus; Compta, Yaroslau; Katzenschlager, Regina; Mas, Natalia; Hofeneder, Dominik; Brücke, Thomas; Bayés, Angels; Wenzel, Karoline; Infante, Jon; Zach, Heidemarie; Pirker, Walter; Posada, Ignacio J; Álvarez, Ramiro; Ispierto, Lourdes; De Fàbregues, Oriol; Callén, Antoni; Palasí, Antoni; Aguilar, Miquel; Martí, Maria José; Valldeoriola, Francesc; Salamero, Manel; Poewe, Werner; Tolosa, Eduardo

    2015-02-01

    Nonmotor symptoms (NMS) in Parkinson's disease (PD) can precede onset of motor symptoms. Relationship between premotor symptoms onset and motor features is limited. Our aim is to describe the presence and perceived onset of NMS in PD as well as their possible association with motor phenotype. Presence and onset of NMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls from 11 Spanish and Austrian centers. Seventeen of thirty-one NMS were more common in patients than controls (P < 0.05). They were usually mild and frequently reported to occur at different time-spans before motor symptoms. Anhedonia, apathy, memory complaints, and inattention occurred more frequently during the 2-year premotor period. Those reported more frequently in the 2- to 10-year premotor period were smell loss, mood disturbances, taste loss, excessive sweating, fatigue, and pain. Constipation, dream-enacting behavior, excessive daytime sleepiness, and postprandial fullness were frequently perceived more than 10 years before motor symptoms. No correlation between NMS burden and motor severity, age, or gender was observed. NMS associated in four clusters: rapid eye movement sleep behavior disorder symptoms-constipation, cognition-related, mood-related, and sensory clusters. No cluster was associated with a specific motor phenotype or severity. NMS are common in early unmedicated PD and frequently reported to occur in the premotor period. They are generally mild, but a patient subgroup showed high NMS burden mainly resulting from cognition-related symptoms. Certain NMS when present at the time of assessment or in the premotor stage, either alone or in combination, allowed discriminating PD from controls.

  3. Clinical Value of NPHS2 Analysis in Early- and Adult-Onset Steroid-Resistant Nephrotic Syndrome

    PubMed Central

    Santín, Sheila; Tazón-Vega, Bárbara; Silva, Irene; Cobo, María Ángeles; Giménez, Isabel; Ruíz, Patricia; García-Maset, Rafael; Ballarín, José

    2011-01-01

    Summary Background and objectives To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. Design, setting, participants, & measurements Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. Results Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio = 2.65; P = 0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. Conclusions NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant. PMID:20947785

  4. Exome Sequencing Frequently Reveals the Cause of Early-Onset Chronic Kidney Disease

    PubMed Central

    Vivante, Asaf; Hildebrandt, Friedhelm

    2016-01-01

    The primary causes of chronic kidney disease (CKD) in children differ from those of adult onset CKD. In the United States the most common diagnostic groups of CKD that manifests before 25 years of age are: i) congenital anomalies of the kidneys and urinary tract (CAKUT) (49.1%), ii) steroid-resistant nephrotic syndrome (SRNS) (10.4%), iii) chronic glomerulonephritis (8.1%), and iv) renal cystic ciliopathies (5.3 %), encompassing >70% of CKD together. Recent findings suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. High-throughput sequencing has very recently rendered identification of causative mutations in this high number of genes feasible. Molecular genetic diagnostics in early onset-CKD (before the age of 25 years) will, i) provide patients and families with a molecular genetic diagnosis, ii) generate new insights into diseases mechanisms, iii) allow etiology-based classification of patient cohorts for clinical studies and, iv) may have consequences for personalized treatment and prevention of CKD. In this review, we will discuss the implications of next-generation sequencing for clinical genetic diagnostics and discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and therapeutic implications. PMID:26750453

  5. Deciphering the mechanism underlying late-onset Alzheimer disease.

    PubMed

    Krstic, Dimitrije; Knuesel, Irene

    2013-01-01

    Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of Aβ accumulation in late-onset AD.

  6. Spinocerebellar ataxia type 13 mutation that is associated with disease onset in infancy disrupts axonal pathfinding during neuronal development.

    PubMed

    Issa, Fadi A; Mock, Allan F; Sagasti, Alvaro; Papazian, Diane M

    2012-11-01

    Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominant disease caused by mutations in the Kv3.3 voltage-gated potassium (K(+)) channel. SCA13 exists in two forms: infant onset is characterized by severe cerebellar atrophy, persistent motor deficits and intellectual disability, whereas adult onset is characterized by progressive ataxia and progressive cerebellar degeneration. To test the hypothesis that infant- and adult-onset mutations have differential effects on neuronal development that contribute to the age at which SCA13 emerges, we expressed wild-type Kv3.3 or infant- or adult-onset mutant proteins in motor neurons in the zebrafish spinal cord. We characterized the development of CaP (caudal primary) motor neurons at ∼36 and ∼48 hours post-fertilization using confocal microscopy and 3D digital reconstruction. Exogenous expression of wild-type Kv3.3 had no significant effect on CaP development. In contrast, CaP neurons expressing the infant-onset mutation made frequent pathfinding errors, sending long, abnormal axon collaterals into muscle territories that are normally innervated exclusively by RoP (rostral primary) or MiP (middle primary) motor neurons. This phenotype might be directly relevant to infant-onset SCA13 because interaction with inappropriate synaptic partners might trigger cell death during brain development. Importantly, pathfinding errors were not detected in CaP neurons expressing the adult-onset mutation. However, the adult-onset mutation tended to increase the complexity of the distal axonal arbor. From these results, we speculate that infant-onset SCA13 is associated with marked changes in the development of Kv3.3-expressing cerebellar neurons, reducing their health and viability early in life and resulting in the withered cerebellum seen in affected children.

  7. Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

    PubMed

    Nakamura, R K; Russell, N J; Shelton, G D

    2012-06-01

    A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog.

  8. Case report: An adult-onset type II citrin deficiency patient in the emergency department

    PubMed Central

    TANG, LUJIA; CHEN, LIANG; WANG, HAIRONG; DAI, LIHUA; PAN, SHUMING

    2016-01-01

    Mutations in the solute carrier family 25 (SLC25A13) gene may result in neonatal intrahepatic cholestasis caused by citrin deficiency and/or adult-onset type II citrullinemia. These conditions are inherited in an autosomal recessive manner. The current case report describes a 43-year-old man who presented with sudden delirium and upper limb weakness. Upon admission, the patient was fully conscious and alert but later lost consciousness subsequent to a sudden convulsive seizure. Hyperammonemia was detected and analysis of the SLC25A13 gene identified an 851del4 mutation. Thus, the possibility of genetic disease should be considered as a potential cause of the symptoms of patients with altered states of consciousness, such as delirium and loss of consciousness, in cases where the cause of the disturbance is unknown. PMID:27347070

  9. Huntington's disease of early onset or juvenile Huntington's disease.

    PubMed

    Gordon, Neil

    2003-10-01

    The presentation of juvenile Huntington's disease can cause diagnostic difficulties. The genetics and pathogenesis of the condition are discussed. The diagnosis will depend on the symptoms raising suspicions and the exclusion of other disorders, especially by genetic studies.

  10. B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis

    PubMed Central

    Schwarz, Alexander; Balint, Bettina; Korporal-Kuhnke, Mirjam; Jarius, Sven; von Engelhardt, Kathrin; Fürwentsches, Alexandra; Bussmann, Cornelia; Ebinger, Friedrich; Haas, Jürgen

    2016-01-01

    Objective: To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS). Methods: In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8–18 years) and 40 patients with adMS (23–65 years) and blood specimens from 66 controls (1–55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA. Results: Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M. Conclusions: We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS. PMID:28053999

  11. Genomewide association study for onset age in Parkinson disease

    PubMed Central

    Latourelle, Jeanne C; Pankratz, Nathan; Dumitriu, Alexandra; Wilk, Jemma B; Goldwurm, Stefano; Pezzoli, Gianni; Mariani, Claudio B; DeStefano, Anita L; Halter, Cheryl; Gusella, James F; Nichols, William C; Myers, Richard H; Foroud, Tatiana

    2009-01-01

    Background Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age. Methods Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication sample of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy. Results Meta-analysis across the three studies detected consistent association (p < 1 × 10-5) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971; p = 5.4 × 10-7) lies between the genes QSER1 and PRRG4. Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851; p = 8.7 × 10-6) which lies in an intron of the AAK1 gene. This gene is closely related to GAK, identified as a possible PD susceptibility gene in the GWAS of the familial PD cases. Conclusion Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis. PMID:19772629

  12. Late-Onset Glycogen Storage Disease Type II (Pompe's Disease) with a Novel Mutation: A Malaysian Experience.

    PubMed

    Fu Liong, Hiew; Abdul Wahab, Siti Aishah; Yakob, Yusnita; Lock Hock, Ngu; Thong, Wong Kum; Viswanathan, Shanthi

    2014-01-01

    Pompe's disease (acid maltase deficiency, glycogen storage disease type II) is an autosomal recessive disorder caused by a deficiency of lysosomal acid α-1,4-glucosidase, resulting in excessive accumulation of glycogen in the lysosomes and cytoplasm of all tissues, most notably in skeletal muscles. We present a case of adult-onset Pompe's disease with progressive proximal muscles weakness over 5 years and respiratory failure on admission, requiring prolonged mechanical ventilation. Electromyography showed evidence of myopathic process with small amplitudes, polyphasic motor unit action potentials, and presence of pseudomyotonic discharges. Muscle biopsy showed glycogen-containing vacuoles in the muscle fibers consistent with glycogen storage disease. Genetic analysis revealed two compound heterozygous mutations at c.444C>G (p.Tyr148∗) in exon 2 and c.2238G>C (p.Trp746Cys) in exon 16, with the former being a novel mutation. This mutation has not been reported before, to our knowledge. The patient was treated with high protein diet during the admission and subsequently showed good clinical response to enzyme replacement therapy with survival now to the eighth year. Conclusion. In patients with late-onset adult Pompe's disease, careful evaluation and early identification of the disease and its treatment with high protein diet and enzyme replacement therapy improve muscle function and have beneficial impact on long term survival.

  13. Adult Height and Childhood Disease

    PubMed Central

    BOZZOLI, CARLOS; DEATON, ANGUS; QUINTANA-DOMEQUE, CLIMENT

    2009-01-01

    Taller populations are typically richer populations, and taller individuals live longer and earn more. In consequence, adult height has recently become a focus in understanding the relationship between health and wealth. We investigate the childhood determinants of population adult height, focusing on the respective roles of income and of disease. Across a range of European countries and the United States, we find a strong inverse relationship between postneonatal (ages 1 month to 1 year) mortality, interpreted as a measure of the disease and nutritional burden in childhood, and the mean height of those children as adults. Consistent with these findings, we develop a model of selection and stunting in which the early-life burden of undernutrition and disease not only is responsible for mortality in childhood but also leaves a residue of long-term health risks for survivors, risks that express themselves in adult height and in late-life disease. The model predicts that at sufficiently high mortality levels, selection can dominate scarring, leaving a taller population of survivors. We find evidence of this effect in the poorest and highest-mortality countries of the world, supplementing recent findings on the effects of the Great Chinese Famine. PMID:20084823

  14. New cardiovascular targets to prevent late onset Alzheimer disease.

    PubMed

    Claassen, Jurgen A H R

    2015-09-15

    The prevalence of dementia rises to between 20% and 40% with advancing age. The dominant cause of dementia in approximately 70% of these patients is Alzheimer disease. There is no effective disease-modifying pharmaceutical treatment for this neurodegenerative disease. A wide range of Alzheimer drugs that appeared effective in animal models have recently failed to show clinical benefit in patients. However, hopeful news has emerged from recent studies that suggest that therapeutic strategies aimed at reducing cardiovascular disease may also reduce the prevalence of dementia due to Alzheimer disease. This review summarizes the evidence for this link between cardiovascular disease and late onset Alzheimer dementia. Only evidence from human research is considered here. Longitudinal studies show an association between high blood pressure and pathological accumulation of the protein amyloid-beta42, and an even stronger association between vascular stiffness and amyloid accumulation, in elderly subjects. Amyloid-beta42 accumulation is considered to be an early marker of Alzheimer disease, and increases the risk of subsequent cognitive decline and development of dementia. These observations could provide an explanation for recent observations of reduced dementia prevalence associated with improved cardiovascular care.

  15. Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease.

    PubMed

    Boentert, Matthias; Prigent, Hélène; Várdi, Katalin; Jones, Harrison N; Mellies, Uwe; Simonds, Anita K; Wenninger, Stephan; Barrot Cortés, Emilia; Confalonieri, Marco

    2016-10-17

    Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors' own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease.

  16. Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease

    PubMed Central

    Boentert, Matthias; Prigent, Hélène; Várdi, Katalin; Jones, Harrison N.; Mellies, Uwe; Simonds, Anita K.; Wenninger, Stephan; Barrot Cortés, Emilia; Confalonieri, Marco

    2016-01-01

    Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors’ own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease. PMID:27763517

  17. Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination

    MedlinePlus

    ... Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  18. [Periodontitis determining the onset and progression of Huntington's disease: review of the literature].

    PubMed

    Rodríguez Coyago, María Lourdes; Sánchez Temiño, Victoria Emilia

    2015-10-27

    Huntington's disease is a neurodegenerative disorder caused by the expansion of a CAG triplet in the huntingtin gene. It presents with physical, cognitive and psychiatric impairment at different ages in the adult, and has a fatal prognosis. Other than the number of triplet repetitions, there seem to be other factors that explain the onset of this disease at an earlier age. It is well known that neuroinflammation has a key role in neurodegenerative disorders; Huntington's disease is not an exception to that rule. Neuroinflammation exacerbates neuronal damage produced by mutation, by initiating aberrant activation of microglia cell, as well as astrocyte and dendritic cell dysfunction; also compromising the blood-brain barrier and activating the complement cascade. The latter as a direct and indirect effect of the mutation and other stimuli such as chronic infections. In this study, periodontitis is presented as a model of chronic oral infection and a systemic inflammation source. We hypothesize the potential role of periodontitis in Huntington's disease, and the mechanisms by which it contributes to the early onset and progress of the disease. We considered experimental studies, systematic reviews, meta-analyses, published in both Spanish and English, obtained from the PubMed and SciELO databases. There are various mechanisms that generate brain inflammation in these patients; mechanisms of innate immunity being especially prominent. Chronic oral-dental infections, such as periodontal disease, may be an exacerbating factor that adds to the neuroinflammation of Huntington'’s disease.

  19. Audiovisual Integration Delayed by Stimulus Onset Asynchrony Between Auditory and Visual Stimuli in Older Adults.

    PubMed

    Ren, Yanna; Yang, Weiping; Nakahashi, Kohei; Takahashi, Satoshi; Wu, Jinglong

    2017-02-01

    Although neuronal studies have shown that audiovisual integration is regulated by temporal factors, there is still little knowledge about the impact of temporal factors on audiovisual integration in older adults. To clarify how stimulus onset asynchrony (SOA) between auditory and visual stimuli modulates age-related audiovisual integration, 20 younger adults (21-24 years) and 20 older adults (61-80 years) were instructed to perform an auditory or visual stimuli discrimination experiment. The results showed that in younger adults, audiovisual integration was altered from an enhancement (AV, A ± 50 V) to a depression (A ± 150 V). In older adults, the alterative pattern was similar to that for younger adults with the expansion of SOA; however, older adults showed significantly delayed onset for the time-window-of-integration and peak latency in all conditions, which further demonstrated that audiovisual integration was delayed more severely with the expansion of SOA, especially in the peak latency for V-preceded-A conditions in older adults. Our study suggested that audiovisual facilitative integration occurs only within a certain SOA range (e.g., -50 to 50 ms) in both younger and older adults. Moreover, our results confirm that the response for older adults was slowed and provided empirical evidence that integration ability is much more sensitive to the temporal alignment of audiovisual stimuli in older adults.

  20. TYROBP genetic variants in early-onset Alzheimer's disease.

    PubMed

    Pottier, Cyril; Ravenscroft, Thomas A; Brown, Patricia H; Finch, NiCole A; Baker, Matt; Parsons, Meeia; Asmann, Yan W; Ren, Yingxue; Christopher, Elizabeth; Levitch, Denise; van Blitterswijk, Marka; Cruchaga, Carlos; Campion, Dominique; Nicolas, Gaël; Richard, Anne-Claire; Guerreiro, Rita; Bras, Jose T; Zuchner, Stephan; Gonzalez, Michael A; Bu, Guojun; Younkin, Steven; Knopman, David S; Josephs, Keith A; Parisi, Joseph E; Petersen, Ronald C; Ertekin-Taner, Nilüfer; Graff-Radford, Neill R; Boeve, Bradley F; Dickson, Dennis W; Rademakers, Rosa

    2016-12-01

    We aimed to identify new candidate genes potentially involved in early-onset Alzheimer's disease (EOAD). Exome sequencing was conducted on 45 EOAD patients with either a family history of Alzheimer's disease (AD, <65 years) or an extremely early age at the onset (≤55 years) followed by multiple variant filtering according to different modes of inheritance. We identified 29 candidate genes potentially involved in EOAD, of which the gene TYROBP, previously implicated in AD, was selected for genetic and functional follow-up. Using 3 patient cohorts, we observed rare coding TYROBP variants in 9 out of 1110 EOAD patients, whereas no such variants were detected in 1826 controls (p = 0.0001), suggesting that at least some rare TYROBP variants might contribute to EOAD risk. Overexpression of the p.D50_L51ins14 TYROBP mutant led to a profound reduction of TREM2 expression, a well-established risk factor for AD. This is the first study supporting a role for genetic variation in TYROBP in EOAD, with in vitro support for a functional effect of the p.D50_L51ins14 TYROBP mutation on TREM2 expression.

  1. Aortoiliac occlusive disease presenting as sudden onset paraplegia.

    PubMed

    Lai, Chien-Hung; Wang, Cheng-Hsien; Wu, Shih-Yun; Shih, Hong-Mo

    2014-07-01

    Thromboembolism and atherosclerotic stenosis both can cause arterial occlusion. Aortoiliac occlusive disease involving bifurcation of the aortoiliac artery induces symptoms of ischemia such as claudication and pain of buttocks and thighs, decreased bilateral femoral pulses, and impotence. Here, we describe a 58-year-old woman with a past history of atrial fibrillation and lacuna stroke with minimal right side weakness. She presented to our emergency department with sudden onset bilateral pain in the legs and paraplegia. A comprehensive examination revealed paresthesia and decreasing bilateral distal pulses. Computed tomographic imaging showed filling defects over the low abdominal aorta just above the bifurcation of the common iliac artery and bilateral femoral arteries. Acute aortic embolic occlusion was suspected. Her symptoms were resolved after emergent thrombectomy for acute limb ischemia. Physicians need to be aware of aortoiliac embolic occlusive disease which may present as acute paraplegia.

  2. Adult Orbital Xanthogranulomatous Disease: A Review with Emphasis on Etiology, Systemic Associations, Diagnostic Tools, and Treatment.

    PubMed

    Kerstetter, Justin; Wang, Jun

    2015-07-01

    Adult orbital xanthogranulomatous diseases are rare entities and encompass a group of disorders with varying manifestations that are poorly understood. Taken as a group, there are non-Langerhans histiocytic disorders (type II) that are diagnosed histologically by the presence of foamy histiocytes, Touton giant cells, and varying degrees of fibrosis. Based on the accompanying systemic associations, there are 4 main categories of adult xanthogranulomatous disease: adult-onset xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. Herein, we discuss the etiopathogenesis, systemic associations, methods of diagnosis, and treatment options for these disorders.

  3. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  4. Fetal nutrition and adult disease.

    PubMed

    Godfrey, K M; Barker, D J

    2000-05-01

    Recent research suggests that several of the major diseases of later life, including coronary heart disease, hypertension, and type 2 diabetes, originate in impaired intrauterine growth and development. These diseases may be consequences of "programming," whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology, and metabolism. Evidence that coronary heart disease, hypertension, and diabetes are programmed came from longitudinal studies of 25,000 UK men and women in which size at birth was related to the occurrence of the disease in middle age. People who were small or disproportionate (thin or short) at birth had high rates of coronary heart disease, high blood pressure, high cholesterol concentrations, and abnormal glucose-insulin metabolism. These relations were independent of the length of gestation, suggesting that cardiovascular disease is linked to fetal growth restriction rather than to premature birth. Replication of the UK findings has led to wide acceptance that low rates of fetal growth are associated with cardiovascular disease in later life. Impaired growth and development in utero seem to be widespread in the population, affecting many babies whose birth weights are within the normal range. Although the influences that impair fetal development and program adult cardiovascular disease remain to be defined, there are strong pointers to the importance of the fetal adaptations invoked when the maternoplacental nutrient supply fails to match the fetal nutrient demand.

  5. Onset of Huntington disease: Can it be purely cognitive?

    PubMed Central

    Paulsen, Jane S.; Long, Jeffrey D.

    2014-01-01

    Knowledge of the cognitive manifestation of Huntington disease has burgeoned over the past two decades. Many studies from independent datasets have shown cognitive impairment is evident prior to motor diagnosis and annual cognitive decline is a robust marker of disease progression. Additionally, cognition is a critical concern to patients and families and is associated with meaningful outcomes including functional capacity, driving, loss of accustomed work and quality of life. In the past few years, Huntington disease animal models of cognition have increased, preparing for preclinical experimental therapeutics with cognitive endpoints. A longitudinal analysis of cognitive variables was conducted with 559 gene-positive cases and 233 controls showing no signs of motor abnormalities over approximately a three year period. Results show there were statistically significant differences in rate of annual change for some cognitive variables, such that the cases group had worsening performance over time. These findings show cognitive deterioration can be seen in persons with the Huntington disease gene expansion with no overt motor signs or symptoms, suggesting that cognitive onset of Huntington disease may precede motor. PMID:25142616

  6. Onset of Huntington's disease: can it be purely cognitive?

    PubMed

    Paulsen, Jane S; Long, Jeffrey D

    2014-09-15

    Knowledge of the cognitive manifestation of Huntington's disease has burgeoned over the past two decades. Many studies from independent datasets have shown that cognitive impairment is evident before motor diagnosis, and annual cognitive decline is a robust marker of disease progression. Additionally, cognition is a critical concern to patients and families and is associated with meaningful outcomes, including functional capacity, driving, loss of accustomed work, and quality of life. In the past few years, Huntington's disease animal models of cognition have increased, preparing for preclinical experimental therapeutics with cognitive endpoints. A longitudinal analysis of cognitive variables was conducted with 559 gene-positive cases and 233 controls showing no signs of motor abnormalities over approximately a 3-year period. Results show statistically significant differences in rate of annual change for some cognitive variables, such that the cases group had worsening performance over time. These findings show that cognitive deterioration can be seen in persons with the Huntington's disease gene expansion with no overt motor signs or symptoms, suggesting that cognitive onset of Huntington's disease may precede motor.

  7. Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

    PubMed Central

    Nunley, Karen A.; Ryan, Christopher M.; Jennings, J. Richard; Aizenstein, Howard J.; Zgibor, Janice C.; Costacou, Tina; Boudreau, Robert M.; Miller, Rachel; Orchard, Trevor J.; Saxton, Judith A.

    2015-01-01

    OBJECTIVE The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS During 2010–2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986–1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6–0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3–0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI

  8. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    PubMed Central

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-01-01

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

  9. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability.

    PubMed

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-08-05

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability.

  10. Adult Onset of Xanthelasmoid Mastocytosis: Report of a Rare Entity

    PubMed Central

    Nabavi, Nafiseh Sadat; Nejad, Masumeh Hosseini; Feli, Shahab; Bakhshoodeh, Behnoosh; Layegh, Pouran

    2016-01-01

    Xanthelasmoid or pseudoxanthomatous mastocytosis is an extremely rare variant of diffuse cutaneous mastocytosis. Herein, we describe an adult male with cutaneous mastocytosis showing multiple widespread yellowish ovoid papules like eruptive xanthoma. A 60-year-old male visited our outpatient clinic with a 1-year history of generalized yellowish, ovoid, and skin color papular eruption located on the trunk, groin, extremities, with the modest pruritus. Vital signs were stable, and Darier's sign was negative. No other subjective and objective signs were detected during the examination. No abnormality was detected in his diagnostic laboratory tests. Skin biopsy was taken, and histopathologic examination revealed proliferation of mast cells with ovoid and spindle nuclei with distinct cytoplasm borders around the capillaries, which was compatible with mastocytosis. Antihistamine was prescribed for pruritus control which was successful, but eruptions were persistent, and even 1-year phototherapy was not useful. PMID:27512209

  11. Childhood-onset (Juvenile) Huntington's disease: A rare case report

    PubMed Central

    Patra, Kailash Chandra; Shirolkar, Mukund Sudhir

    2015-01-01

    Huntington's disease (HD) is a rare dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic) movements, neuropsychiatric manifestations, and dementia. It is caused by an unstable CAG repeat expansion in the gene IT15 which encodes a Huntingtin protein. We present a case of a 9 year old boy who had developmental regression starting from the age of 8 years of age along with resistant seizures and signs of cerebellar involvement with absence of chorea and is on anticonvulsants, baclofen, and tetrabenzine. As is expected in a case of childhood-onset HD, our patient is rapidly deteriorating and is currently in the terminal phase of his illness along with resistant convulsions. PMID:26557176

  12. Childhood-onset (Juvenile) Huntington's disease: A rare case report.

    PubMed

    Patra, Kailash Chandra; Shirolkar, Mukund Sudhir

    2015-01-01

    Huntington's disease (HD) is a rare dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic) movements, neuropsychiatric manifestations, and dementia. It is caused by an unstable CAG repeat expansion in the gene IT15 which encodes a Huntingtin protein. We present a case of a 9 year old boy who had developmental regression starting from the age of 8 years of age along with resistant seizures and signs of cerebellar involvement with absence of chorea and is on anticonvulsants, baclofen, and tetrabenzine. As is expected in a case of childhood-onset HD, our patient is rapidly deteriorating and is currently in the terminal phase of his illness along with resistant convulsions.

  13. Links of autophagy dysfunction to inflammatory bowel disease onset

    PubMed Central

    El-Khider, Faris; McDonald, Christine

    2017-01-01

    Introduction Autophagy is a cellular stress response that plays key roles in physiological processes, such as adaptation to starvation, degradation of aberrant proteins or organelles, anti-microbial defense, protein secretion, and innate and adaptive immunity. Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including inflammatory bowel disease (IBD). Genetic studies have identified multiple IBD-associated risk loci that include genes required for autophagy, and several lines of evidence demonstrate that autophagy is impaired in IBD patients. How dysfunctional autophagy contributes to IBD onset is currently under investigation by researchers. Key messages Dysfunctional autophagy has been identified to play a role IBD pathogenesis by altering processes that include: (1) intracellular bacterial killing, (2) anti-microbial peptide secretion by Paneth cells, (3) pro-inflammatory cytokine production by macrophages, (4) antigen presentation by dendritic cells, (5) goblet cell function, and (6) the endoplasmic reticulum stress response in enterocytes. The overall effect of dysregulation of these processes varies by cell type, stimulus, as well as cellular context. Manipulation of the autophagic pathway may provide a new avenue in the search for effective therapies for IBD. Conclusion Autophagy plays multiple roles in IBD pathogenesis. A better understanding of the role of autophagy in IBD patients may provide better subclassification of IBD phenotypes and novel approaches to disease management. PMID:26982478

  14. [Crohn's disease with the onset resembling systemic lupus erythematosus].

    PubMed

    Shimizu, T; Nishinarita, S; Son, K; Tomita, Y; Yoshihiro; Matsukawa; Kitamura, N; Horie, T; Baba, M; Hiranuma, M

    1999-06-01

    We described a 37-year-old man with Crohn's disease (CD) resembling systemic lupus erythematosus (SLE) at his disease onset. He was admitted to the municiple Akiru Hospital in October 1986 by fever, aphtous oral ulcerations, sore throat and polyarthralgia. Hematologic examination showed leukocytopenia, lymphocytopenia, positive tests for antinuclear antibody, anti-DNA antibody and LE cell phenomenon. He has had episodes of convulsion and conciousness loss of unknown etiology when he was 17 years old. The diagnosis of SLE was made, and oral medication of prednisolone was started. Several weeks later, most of symptoms and autoantibodies disappeared, although the oral aphtous ulcerations and leukocytopenia remained. In May 1987, he admitted to the other hospital because of bloody vomiting. Endoscopic examination showed the esophagial ulceration, and histology of biopsied-specimen was nonspecific esophagitis. The combination of prednisolone and oral cyclophosphamide or methotrexate was employed thereafter. However, the leukocytopenia, oral aphtous ulceration and esophagial ulceration continued in spite of these treatments. All the immunosuppressive treatment was stopped at March 1992. In October 1995, he admitted to our hospital because of body weight loss and continuous diarrhea with occasional bloody stool. Barium enema and endoscopic examination of the colon revealed the findings compatible with CD. The patient responded favorably to methylprednisolone pulse therapy followed by oral sulphasalazine. This case indicated that cases with inflammatory bowel diseases like CD could show similar clinical signs and symptoms to SLE, and in some cases of CD might satisfied the classification of criteria for SLE.

  15. Juvenile Huntington's disease: does a dosage-effect pathogenic mechanism differ from the classical adult disease?

    PubMed

    Squitieri, Ferdinando; Frati, Luigi; Ciarmiello, Andrea; Lastoria, Secondo; Quarrell, Oliver

    2006-02-01

    Huntington's disease (HD) is caused by a CAG repeat mutation translating as a polyglutamine (poly(Q)) expansion in the huntingtin protein, whose main pathogenic mechanism is a gain of toxic function. In the case of large expansions beyond 60 repeats onset may result in juvenile HD (JHD, onset before 20 years of age). However, the triplet number does not represent the only onset modifier even in case of large expansions, mechanisms other than the size of the mutation contribute to the phenotype. In this review we discuss the possibility that some of the pathogenic mechanisms contributing to age at onset and progression may differ in the early onset HD compared with the classical adult pathology.

  16. Early-Onset Psychoses: Comparison of Clinical Features and Adult Outcome in 3 Diagnostic Groups

    ERIC Educational Resources Information Center

    Ledda, Maria Giuseppina; Fratta, Anna Lisa; Pintor, Manuela; Zuddas, Alessandro; Cianchetti, Carlo

    2009-01-01

    A comparison of clinical features and adult outcome in adolescents with three types of psychotic disorders: schizophrenic (SPh), schizoaffective (SA) and bipolar with psychotic features (BPP). Subjects (n = 41) were finally diagnosed (DSM-IV criteria) with SPh (n = 17), SA (n = 11) or BPP (n = 13). Clinical evaluation took place at onset and at a…

  17. Physical Therapists' Perceptions of Providing Services to Adults with Childhood-Onset Neuromotor Disabilities

    ERIC Educational Resources Information Center

    Compton-Griffith, Kelsi N.; Cicirello, Nancy A.; Turner, Anne

    2011-01-01

    Adults with childhood-onset neuromotor disabilities face problems accessing health care services. There are often challenges finding primary care providers or specialized providers, such as physical therapists, who are knowledgeable about neuromotor disabilities. The purpose of this study was to determine the perceptions of physical therapists…

  18. Adult-Onset Antisocial Behavior Trajectories: Associations with Adolescent Family Processes and Emerging Adulthood Functioning

    ERIC Educational Resources Information Center

    Mata, Andrea D.; van Dulmen, Manfred H. M.

    2012-01-01

    Guided by conceptual and empirical work on emerging adulthood, this study investigated the role of closeness to mother and father and behavioral autonomy during adolescence on the development of adult-onset antisocial behavior. Using data from the National Longitudinal Study of Adolescent Health (Add Health), we identified four aggressive…

  19. Ethical issues and policy analysis for genetic testing: Huntington's disease as a paradigm for diseases with a late onset.

    PubMed

    Lilani, Anjali

    2005-01-01

    This paper discusses the main ethical issues that arise when testing for genetic diseases with a late adult onset, such as Huntington's disease, take place. It is imperative to study genetic testing for HD and similar diseases because of the potential to influence future medical advances and the growing number of individuals who are considered pre-symptomatic. The main ethical issues are consent and privacy, prenatal testing and its implications, in addition to insurance discrimination. These issues are viewed from the perspective of genetic counselors, patients, the families of patients, and insurance companies. Policies put forth by the United States National Society of Genetic Counselors ("NSGC"), the Task Force on Genetic Testing, and the President's Council for Bioethics are also analyzed. Finally, new recommendations are proposed in order to ameliorate the ethical dilemmas encountered in genetic testing. These recommendations are largely based on existing policies and therefore involve amending current policies rather than revamping them.

  20. Adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia: report of five cases and a new mutation.

    PubMed

    Kleinfeld, Kirk; Mobley, Bret; Hedera, Peter; Wegner, Adam; Sriram, Subramaniam; Pawate, Siddharama

    2013-02-01

    The objective of this work is to report on a series of five patients with adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia (ALSP). ALSP is a rare adult-onset leukodystrophy, which encompasses hereditary diffuse leukoencephalopathy with axonal spheroids and pigmentary orthochromatic leukodystrophy. This was a retrospective chart review and literature review. Five previously healthy women presented with a rapidly progressive neurological disorder at ages 39, 37, 40, 30, and 47, respectively. All five individuals were initially diagnosed as suffering from multiple sclerosis. The clinical courses of the five patients were dominated by progressive spastic quadriparesis (patient 5, newly diagnosed, has paraparesis at this time) and dementia. Brain magnetic resonance imaging (MRI) showed diffuse cerebral atrophy, corpus callosal atrophy, and diffuse T2 hyperintensities in the subcortical and periventricular white matter with no gadolinium enhancing lesions. Three patients showed involvement of pyramidal tracts from motor cortex to the brainstem. Cerebrospinal fluid was normal in all cases. Diagnosis of ALSP was established by biopsy (two cases) and autopsy (two cases). Histopathology showed the presence of neuroaxonal spheroids in all four cases and pigmented glia in three. In the fifth case, diagnosis was established by genetic analysis alone that showed a disease-causing mutation in the colony-stimulating factor 1 receptor (CSF1R) gene. Genetic analysis was done in three patients with available DNA, and identified the disease-causing mutation in all three, including a novel mutation F828S. ALSP may be suspected in adults with rapid to subacute progression of neurological disease when (1) MRI shows corpus callosal atrophy on a background of generalized brain atrophy and diffuse white matter disease without postcontrast enhancement, (2) CSF studies are normal, and (3) studies for systemic inflammatory diseases and specific leukodystrophies are

  1. Mastocytosis in children and adults: clinical disease heterogeneity

    PubMed Central

    Nedoszytko, Bogusław; Górska, Aleksandra; Żawrocki, Anton; Sobjanek, Michał; Kozlowski, Dariusz

    2012-01-01

    Mastocytosis is a clonal disease of the hematopoietic stem cell. The condition consists of a heterogeneous group of disorders characterized by a pathological accumulation of mast cells in tissues including the skin, bone marrow, liver, spleen and the lymph nodes. Mastocytosis is a rare disease which occurs both in children and adults. Childhood onset mastocytosis is usually cutaneous and transient while in adults the condition commonly progresses to a systemic form. The heterogeneity of clinical presentation of mastocytosis is typically related to the tissue mast cell burden, symptoms due to the release of mast cell mediators, the type of skin lesions, the patient's age at the onset and associated haematological disorders. Therefore, a multidisciplinary approach is recommended. The present article provides an overview of clinical symptoms, diagnostic criteria and treatment of mastocytosis to facilitate the diagnosis and management of mastocytosis patients in clinical practice. PMID:22852012

  2. Mastocytosis in children and adults: clinical disease heterogeneity.

    PubMed

    Lange, Magdalena; Nedoszytko, Bogusław; Górska, Aleksandra; Zawrocki, Anton; Sobjanek, Michał; Kozlowski, Dariusz

    2012-07-04

    Mastocytosis is a clonal disease of the hematopoietic stem cell. The condition consists of a heterogeneous group of disorders characterized by a pathological accumulation of mast cells in tissues including the skin, bone marrow, liver, spleen and the lymph nodes. Mastocytosis is a rare disease which occurs both in children and adults. Childhood onset mastocytosis is usually cutaneous and transient while in adults the condition commonly progresses to a systemic form. The heterogeneity of clinical presentation of mastocytosis is typically related to the tissue mast cell burden, symptoms due to the release of mast cell mediators, the type of skin lesions, the patient's age at the onset and associated haematological disorders. Therefore, a multidisciplinary approach is recommended. The present article provides an overview of clinical symptoms, diagnostic criteria and treatment of mastocytosis to facilitate the diagnosis and management of mastocytosis patients in clinical practice.

  3. Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension.

    PubMed

    Veerbeek, Jan H W; Hermes, Wietske; Breimer, Anath Y; van Rijn, Bas B; Koenen, Steven V; Mol, Ben W; Franx, Arie; de Groot, Christianne J M; Koster, Maria P H

    2015-03-01

    Observational studies have shown an increased lifetime risk of cardiovascular disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This risk is related to the severity of the pregnancy-related hypertensive disease and gestational age at onset. However, it has not been investigated whether these differences in CVD risk factors are already present at postpartum cardiovascular screening. We evaluated postpartum differences in CVD risk factors in 3 subgroups of patients with a history of hypertensive pregnancy. We compared the prevalence of common CVD risk factors postpartum among 448 women with previous early-onset preeclampsia, 76 women with previous late-onset preeclampsia, and 224 women with previous pregnancy-induced hypertension. Women with previous early-onset preeclampsia were compared with women with late-onset preeclampsia and pregnancy-induced hypertension and had significantly higher fasting blood glucose (5.29 versus 4.80 and 4.83 mmol/L), insulin (9.12 versus 6.31 and 6.7 uIU/L), triglycerides (1.32 versus 1.02 and 0.97 mmol/L), and total cholesterol (5.14 versus 4.73 and 4.73 mmol/L). Almost half of the early-onset preeclampsia women had developed hypertension, as opposed to 39% and 25% of women in the pregnancy-induced hypertension and late-onset preeclampsia groups, respectively. Our data show differences in the prevalence of common modifiable CVD risk factors postpartum and suggest that prevention strategies should be stratified according to severity and gestational age of onset for the hypertensive disorders of pregnancy.

  4. Adult-onset nemaline rods in a patient treated for suspected dermatomyositis: study with two-dimensional electrophoresis

    SciTech Connect

    Danon, M.J.; Giometti, C.S.; Manaligod, J.R.; Perurena, O.H.; Skosey, J.L.

    1981-12-01

    A 65-year-old woman with progressive muscle weakness and a diffuse rash of three years' duration was examined. Muscle tissue was studied with histochemical techniques, phase-contrast microscopy, electron microscopy, and two-dimensional electrophoresis. Histochemical studies showed numerous nemaline rods, with a normal ratio of types I and II fibers. Two-dimensional electrophoresis revealed abnormalities in the myosin light chain and tropomyosin protein patterns when compared with normal and diseased muscle biopsy samples, including those from two patients with adult-onset dermatomyositis.

  5. Medical therapy in adults with congenital heart disease.

    PubMed

    Book, Wendy M; Shaddy, Robert E

    2014-01-01

    Heart failure is a common late complication in adults with congenital heart defects, both repaired and unrepaired. The onset of clinical heart failure is associated with increased morbidity and mortality. Some patients with congenital heart disease may benefit from medications shown to improve survival in the population with acquired heart failure, but these same therapies may be of no benefit to other patients. Further studies are needed to better guide the choice of medical therapies.

  6. Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies.

    PubMed

    Yokoyama, Jennifer S; Lam, Ernest T; Ruhe, Alison L; Erdman, Carolyn A; Robertson, Kathryn R; Webb, Aubrey A; Williams, D Colette; Chang, Melanie L; Hytönen, Marjo K; Lohi, Hannes; Hamilton, Steven P; Neff, Mark W

    2012-09-01

    Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging dogs (8-10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09 × 10(-13)). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-κB pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS-guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders.

  7. A nonsense mutation of human XRCC4 is associated with adult-onset progressive encephalocardiomyopathy

    PubMed Central

    Bee, Leonardo; Nasca, Alessia; Zanolini, Alice; Cendron, Filippo; d'Adamo, Pio; Costa, Rodolfo; Lamperti, Costanza; Celotti, Lucia; Ghezzi, Daniele; Zeviani, Massimo

    2015-01-01

    We studied two monozygotic twins, born to first cousins, affected by a multisystem disease. At birth, they both presented with bilateral cryptorchidism and malformations. Since early adulthood, they developed a slowly progressive neurological syndrome, with cerebellar and pyramidal signs, cognitive impairment, and depression. Dilating cardiomyopathy is also present in both. By whole-exome sequencing, we found a homozygous nucleotide change in XRCC4 (c.673C>T), predicted to introduce a premature stop codon (p.R225*). XRCC4 transcript levels were profoundly reduced, and the protein was undetectable in patients' skin fibroblasts. XRCC4 plays an important role in non-homologous end joining of DNA double-strand breaks (DSB), a system that is involved in repairing DNA damage from, for example, ionizing radiations. Gamma-irradiated mutant cells demonstrated reduction, but not abolition, of DSB repair. In contrast with embryonic lethality of the Xrcc4 KO mouse, nonsense mutations in human XRCC4 have recently been associated with primordial dwarfism and, in our cases, with adult-onset neurological impairment, suggesting an important role for DNA repair in the brain. Surprisingly, neither immunodeficiency nor predisposition to malignancy was reported in these patients. PMID:25872942

  8. Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation

    PubMed Central

    Fujita, Yuko; Ishima, Tamaki; Hashimoto, Kenji

    2016-01-01

    Prenatal maternal infection contributes to the etiology of schizophrenia, with D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, playing a role in the pathophysiology of this disease. We examined whether supplementation with D-serine during juvenile and adolescent stages could prevent the onset of cognitive deficits, prodromal and the core symptoms of schizophrenia in adult offspring after maternal immune activation (MIA). Juvenile offspring exposed prenatally to poly(I:C) showed reduced expression of NMDA receptor subunits in the hippocampus. Supplementing drinking water with D-serine (600 mg/L from P28 to P56) prevented the onset of cognitive deficits in adult offspring after MIA, in a significant manner. This study shows that supplementing offspring with D-serine during juvenile and adolescent stages could prevent the onset of psychosis in adulthood, after MIA. Therefore, early intervention with D-serine may prevent the occurrence of psychosis in high-risk subjects. PMID:27853241

  9. Genome scan in familial late-onset Alzheimer's disease: a locus on chromosome 6 contributes to age-at-onset.

    PubMed

    Zhao, Wei; Marchani, Elizabeth E; Cheung, Charles Y K; Steinbart, Ellen J; Schellenberg, Gerard D; Bird, Thomas D; Wijsman, Ellen M

    2013-03-01

    Alzheimer's disease (AD) is a common, genetically complex, fatal neurodegenerative disorder of late life. Although several genes are known to play a role in early-onset AD, identification of the genetic basis of late onset AD (LOAD) has been challenging, with only the APOE gene known to have a high contribution to both AD risk and age-at-onset. Here, we present the first genome-scan analysis of the complete, well-characterized University of Washington LOAD sample of 119 pedigrees, using age-at-onset as the trait of interest. The analysis approach used allows for a multilocus trait model while at the same time accommodating age censoring, effects of APOE as a known genetic covariate, and full pedigree and marker information. The results provide strong evidence for linkage of loci contributing to age-at-onset to genomic regions on chromosome 6q16.3, and to 19q13.42 in the region of the APOE locus. There was evidence for interaction between APOE and the locus on chromosome 6q and suggestive evidence for linkage to chromosomes 11p13, 15q12-14, and 19p13.12. These results provide the first independent confirmation of an AD age-at-onset locus on chromosome 6 and suggest that further efforts towards identifying the underlying causal locus or loci are warranted.

  10. Procedural memory in recent-onset Parkinson's disease.

    PubMed

    Thomas-Ollivier, V; Reymann, J M; Le Moal, S; Schück, S; Lieury, A; Allain, H

    1999-01-01

    Parkinson's disease is accompanied by cognitive disorders which may affect procedural memory. Procedural memory uses a specific knowledge resource that expresses itself through pre-established acting procedures. The aim of this study was to better define the characteristics of procedural memory, first of all, by trying to determine the level of involvement of that memory in the acquisition process (during learning and/or during procedure maintenance), then by specifying the effect of the type of resource involved (verbal or motor). To achieve this, we compared the mnestic performances of 20 recent-onset parkinsonian patients with those of 20 healthy controls, using two memory tasks with a fixed rule (poetry, visuomotor tracking). Result analysis revealed that parkinsonian patients had more difficulty than controls in learning the two rules, regardless of the material involved. Their deficiencies were often associated with an impairment of executive functions, and the procedural memory problems described in parkinsonian patients are linked to the involvement of these resources in the various tasks.

  11. Age-At-Onset Linkage Analysis in Caribbean Hispanics with Familial Late-Onset Alzheimer’s Disease

    PubMed Central

    Lee, Joseph H.; Barral, Sandra; Cheng, Rong; Chacon, Inara; Santana, Vincent; Williamson, Jennifer; Lantigua, Rafael; Medrano, Martin; Jimenez-Velazquez, Ivonne Z.; Stern, Yaakov; Tycko, Benjamin; Rogaeva, Ekaterina; Wakutani, Yosuke; Kawarai, Toshitaka; St George-Hyslop, Peter; Mayeux, Richard

    2009-01-01

    The aim of the study was to identify chromosomal regions containing putative genetic variants influencing age-at-onset in familial late-onset Alzheimer’s disease. Data from a genome-wide scan that included genotyping of APOE was analyzed in 1,161 individuals from 209 families of Caribbean Hispanic ancestry with a mean age-at-onset of 73.3 years multiply affected by late-onset Alzheimer’s disease. Two-point and multipoint analyses were conducted using variance component methods from 376 microsatellite markers with an average inter-marker distance of 9.3 cM. Family-based test of association were also conducted for the same set of markers. Age-at-onset of symptoms among affected individuals was used as the quantitative trait. Our results showed that the presence of APOE-ε4 lowered the age-at-onset by three years. Using linkage analysis strategy, the highest LOD scores were obtained using a conservative definition of LOAD at 5q15 (LOD 3.1) 17q25.1 (LOD=2.94) and 14q32.12 (LOD=2.36) and 7q36.3 (LOD=2.29) in covariate adjusted models that included APOE-ε4. Both linkage and family-based association identified 17p13 as a candidate region. In addition, family-based association analysis showed markers at 12q13 (p=0.00002), 13q (p=0.00043) and 14q23 (p=0.00046) to be significantly associated with age at onset. The current study supports the hypothesis that there are additional genetic loci that could influence age-at-onset of late onset Alzheimer’s disease. The novel loci at 5q15, 17q25.1, 13q and 17p13, and the previously reported loci at 7q36.3, 12q13, 14q23 and 14q32 need further investigation. PMID:17940814

  12. Longitudinal changes in medical complications in adults with pediatric-onset spinal cord injury

    PubMed Central

    Hwang, Miriam; Zebracki, Kathy; Chlan, Kathleen M.; Vogel, Lawrence C.

    2014-01-01

    Objectives To determine longitudinal changes in the occurrence of medical complications in adults with pediatric-onset spinal cord injury (SCI). Design Longitudinal study of long-term outcomes. Setting Community. Participants Individuals who had sustained an SCI before age 19, were 23 years of age or older at initial interview, and followed annually between 1996 and 2011. They were classified into four American Spinal Injury Association (ASIA) Impairment Scale (AIS) severity groups: C1–4 AIS ABC, C5–8 AIS ABC, T1–S5 AIS ABC, AIS D. Outcome measures Generalized estimating equation (GEE) models were formulated to obtain the odds ratio (OR) of having a medical complication over time. Results A total of 1793 interviews were conducted among 226 men and 125 women (86% Caucasian; age at baseline, 26.7 ± 3.6 years; time since injury at baseline, 12.9 ± 5.2 years). Odds of complication occurrence over time varied among severity groups, with increased ORs of severe urinary tract infection (1.05, confidence interval (CI) 1.02–1.09), autonomic dysreflexia (AD) (1.09, CI 1.05–1.14), spasticity (1.06, CI 1.01–1.11), pneumonia/respiratory failure (1.09, CI 1.03–1.16), and hypertension/cardiac disease (1.07, CI 1.01–1.15) in the C1-4 ABC group; AD (1.08, CI 1.04–1.13) and pneumonia/respiratory failure (1.09, CI 1.02–1.16) in the C5–8 ABC group; and hypertension/cardiac disease (1.08, CI 1.02–1.14) in the T1–S5 ABC group. Upper extremity joint pain had increased odds of occurrence in all injury severity groups. Conclusion The significantly increased odds of having medical complications over time warrants awareness of risk factors and implementation of preventive measures to avoid adverse consequences of complications and to maintain independence in individuals with pediatric-onset SCI. PMID:24090490

  13. Effects of Age, Gender, Bolus Volume, Bolus Viscosity, and Gustation on Swallowing Apnea Onset Relative to Lingual Bolus Propulsion Onset in Normal Adults

    ERIC Educational Resources Information Center

    Hiss, Susan G.; Strauss, Monica; Treole, Kathleen; Stuart, Andrew; Boutilier, Susan

    2004-01-01

    The purpose of this study was to ascertain the normal relation of swallowing apnea (SA) onset relative to lingual bolus propulsion along with factors that may alter this relation. Forty adults, composed of 10 men and 10 women in each of 2 age groups (i.e., 20-30 and 63-79 years) participated. SA onset was assessed during 5- and 20-ml bolus volumes…

  14. Polygenic risk of Parkinson disease is correlated with disease age at onset

    PubMed Central

    Escott‐Price, Valentina; Nalls, Mike A.; Morris, Huw R.; Lubbe, Steven; Brice, Alexis; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Hardy, John; Singleton, Andrew B.

    2015-01-01

    Objective We have investigated the polygenic architecture of Parkinson disease (PD) and have also explored the potential relationship between an individual's polygenic risk score and their disease age at onset. Methods This study used genotypic data from 4,294 cases and 10,340 controls obtained from the meta‐analysis of PD genome‐wide association studies. Polygenic score analysis was performed as previously described by the International Schizophrenia Consortium, testing whether the polygenic score alleles identified in 1 association study were significantly enriched in the cases relative to the controls of 3 independent studies. Linear regression was used to investigate the relationship between an individual's polygenic score for PD risk alleles and disease age at onset. Results Our polygenic score analysis has identified significant evidence for a polygenic component enriched in the cases of each of 3 independent PD genome‐wide association cohorts (minimum p = 3.76 × 10−6). Further analysis identified compelling evidence that the average polygenic score in patients with an early disease age at onset was significantly higher than in those with a late age at onset (p = 0.00014). Interpretation This provides strong support for a large polygenic contribution to the overall heritable risk of PD and also suggests that early onset forms of the illness are not exclusively caused by highly penetrant Mendelian mutations, but can also be contributed to by an accumulation of common polygenic alleles with relatively low effect sizes. Ann Neurol 2015;77:582–591 PMID:25773351

  15. How does dementia onset in parents influence unmarried adult children's wealth.

    PubMed

    Arora, Kanika

    2016-03-01

    There is a growing concern that long-term care (LTC) needs of older adults lead to negative financial consequences for their family members. This paper examines whether the onset of dementia in parents influences wealth change among unmarried adult children regardless of their status as informal caregivers. Longitudinal data from seven waves (1998-2010) of the Health and Retirement Study (1540 person-wave observations) are used to analyze this question. Unconditional quantile regressions demonstrate that as a result of parental dementia diagnosis, unmarried adult children have lower wealth accumulation above the median of the wealth change distribution. These effects are more pronounced for unmarried adult children without siblings. Further, this response is observed to persist in the subsequent period as well. Both losses in labor income and nursing home expenditures may play a role in leading to wealth declines.

  16. Non-motor symptoms in patients with adult-onset focal dystonia: Sensory and psychiatric disturbances.

    PubMed

    Conte, Antonella; Berardelli, Isabella; Ferrazzano, Gina; Pasquini, Massimo; Berardelli, Alfredo; Fabbrini, Giovanni

    2016-01-01

    Dystonia is characterized by the presence of involuntary muscle contractions that cause abnormal movements and posture. Adult onset focal dystonia include cervical dystonia, blepharospasm, arm dystonia and laryngeal dystonia. Besides motor manifestations, patients with focal dystonia frequently also display non-motor signs and symptoms. In this paper, we review the evidence of sensory and psychiatric disturbances in adult patients with focal dystonia. Clinical studies and neurophysiological investigations consistently show that the sensory system is involved in dystonia. Several studies have also demonstrated that neuropsychiatric disorders, particularly depression and anxiety, are more frequent in patients with focal dystonia, whereas data on obsessive compulsive disorders are more contrasting.

  17. What can we learn from study of Alzheimer's disease in patients with Down syndrome for early-onset Alzheimer's disease in the general population?

    PubMed Central

    2011-01-01

    The clinical and scientific study of dementia in adults with Down syndrome led to the development of the amyloid hypothesis as a fundamental concept in Alzheimer's disease pathogenesis. The journey started with the discovery of the structure and metabolic processing of β-amyloid brain deposits associated with Alzheimer's dementia in adults with Down syndrome, and then the prediction and confirmation of the amyloid precursor protein gene on chromosome 21. The processes and genes responsible for tau hyperphosphorylation contributing to toxic brain deposits were additionally identified. With increasing sophistication in genetic experimental techniques, additional mechanisms associated with excessive amyloid deposits were postulated and tested in brains of people with Down syndrome and Alzheimer's disease and in those with early-onset Alzheimer's disease. This in turn led to the proposal and testing for particular genetic defects associated with familial early-onset Alzheimer's disease. Nearly 200 genetic causes of early-onset types of Alzheimer's disease have since been identified. Only a minority of these causes are on chromosome 21, although the aetiology of excess amyloid production remains fundamental to their pathogenesis. Knowledge of the pathogenic mechanisms of Alzheimer's disease in predisposed families and in people with Down syndrome is a step closer to prevention or cure of this devastating disease. PMID:21542885

  18. Clustering and age of onset in familial late onset Alzheimer`s disease are determined at the apoliopoprotein E locus

    SciTech Connect

    Houlden, H.; Rossor, M.

    1994-09-01

    Recent work has demonstrated that the apolipoprotein E (ApoE) genotype is of great importance in the etiology of Alzheimer`s disease (AD). Thus, inheritance of the ApoE4 allele predisposes to the occurrences of late onset disease and decreases the onset age in families with pathogenic mutations in the amyloid precursor protein gene. We analysed ApoE genotypes in 35 families multiply affected by AD and confirm that familial clustering in late onset AD is associated with the ApoE4 allele. This allele occurs in the great majority (82%) of late onset familial Alzheimer cases. Elderly unaffected sibs (80-90 years) have an allele frequency that is not significantly different to that of normal controls. Data presented from our family sets together previously published data is suggestive that the effect of a single ApoE4 allele is to increase the risk of developing AD by an amount equivalent to 5 years and that the effect of ApoE4 homozygosity is to increase the risk of developing AD by an amount equivalent to 10 years of age. Data shows significant difference between the frequency of the ApoE4 allele in the familial AD probands and controls and in both sets of unaffected sibs, p<0.01.

  19. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells

    PubMed Central

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole

    2016-01-01

    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington’s disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions. PMID:26863614

  20. Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats.

    PubMed

    Mustroph, Martina L; King, Michael A; Klein, Ronald L; Ramirez, Julio J

    2012-07-15

    Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics.

  1. Associations between DSM-IV mental disorders and subsequent heart disease onset: beyond depression

    PubMed Central

    Scott, Kate M.; de Jonge, Peter; Alonso, Jordi; Viana, Maria Carmen; Liu, Zhaorui; O’Neill, Siobhan; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; Caldas-de-Almeida, Jose Miguel; Stein, Dan J.; de Girolamo, Giovanni; Florescu, Silvia E.; Hu, Chiyi; Taib, Nezar Ismet; Lépine, Jean-Pierre; Levinson, Daphna; Matschinger, Herbert; Medina-Mora, Maria Elena; Piazza, Marina; Posada-Villa, José A.; Uda, Hidenori; Wojtyniak, Bogdan J.; Lim, Carmen C. W.; Kessler, Ronald C.

    2013-01-01

    Background Prior studies on the depression-heart disease association have not usually used diagnostic measures of depression, nor taken other mental disorders into consideration. As a result, it is not clear whether the association between depression and heart disease onset reflects a specific association, or the comorbidity between depression and other mental disorders. Additionally, the relative magnitude of associations of a range of mental disorders with heart disease onset is unknown. Methods Face-to-face household surveys were conducted in 19 countries (n=52,095; person years=2,141,194). The Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Heart disease was indicated by self-report of physician’s diagnosis, or self-report of heart attack, together with their timing (year). Survival analyses estimated associations between first onset of mental disorders and subsequent heart disease onset. Results After comorbidity adjustment, depression, panic disorder, specific phobia, post-traumatic stress disorder and alcohol use disorders were associated with heart disease onset (ORs 1.3–1.6). Increasing number of mental disorders was associated with heart disease in a dose-response fashion. Mood disorders and alcohol abuse were more strongly associated with earlier onset than later onset heart disease. Associations did not vary by gender. Conclusions Depression, anxiety and alcohol use disorders were significantly associated with heart disease onset; depression was the weakest predictor. If confirmed in future prospective studies, the breadth of psychopathology’s links with heart disease onset has substantial clinical and public health implications. PMID:23993321

  2. Fetal programming of adult disease: implications for prenatal care.

    PubMed

    Lau, Christopher; Rogers, John M; Desai, Mina; Ross, Michael G

    2011-04-01

    The obesity epidemic, including a marked increase in the prevalence of obesity among pregnant women, represents a critical public health problem in the United States and throughout the world. Over the past two decades, it has been increasingly recognized that the risk of adult health disorders, particularly metabolic syndrome, can be markedly influenced by prenatal and infant environmental exposures (ie, developmental programming). Low birth weight, together with infant catch-up growth, is associated with a significant risk of adult obesity and cardiovascular disease, as well as adverse effects on pulmonary, renal, and cerebral function. Conversely, exposure to maternal obesity or high birth weight also represents an increased risk for childhood and adult obesity. In addition, fetal exposure to select chemicals (eg, phytoestrogens) or environmental pollutants (eg, tobacco smoke) may affect the predisposition to adult disease. Animal models have confirmed human epidemiologic findings and provided insight into putative programming mechanisms, including altered organ development, cellular signaling responses, and epigenetic modifications (ie, control of gene expression without modification of DNA sequence). Prenatal care is transitioning to incorporate goals of optimizing maternal, fetal, and neonatal health to prevent or reduce adult-onset diseases. Guidelines regarding optimal pregnancy nutrition and weight gain, management of low- and high-fetal-weight pregnancies, use of maternal glucocorticoids, and newborn feeding strategies, among others, have yet to fully integrate long-term consequences on adult health.

  3. Parental smoking in pregnancy and the risks of adult-onset hypertension.

    PubMed

    de Jonge, Layla L; Harris, Holly R; Rich-Edwards, Janet W; Willett, Walter C; Forman, Michele R; Jaddoe, Vincent W V; Michels, Karin B

    2013-02-01

    Fetal exposure to parental smoking may lead to developmental adaptations and promote various diseases in later life. This study evaluated the associations of parental smoking during pregnancy with the risk of hypertension in the daughter in adulthood, and assessed whether these associations are explained by birth weight or body weight throughout life. We used data on 33086 participants of the Nurses' Health Study II and the Nurses' Mothers' Cohort. Cox proportional hazards models were used to examine the associations of maternal and paternal smoking during pregnancy with the nurse daughter, with self-reported physician-diagnosed hypertension from 1989 until 2007. Overall, 8575 (25.9%) mothers and 18874 (57.0%) fathers smoked during pregnancy. During follow-up, 7825 incident cases of adult-onset hypertension were reported. Both maternal and paternal smoking of ≥ 15 cigarettes/d during pregnancy were associated with increased risks of hypertension (rate ratio, 1.19; 95% CI, 1.09-1.29; and rate ratio, 1.18; 95% CI, 1.12-1.25, respectively) in the age-adjusted models. Further adjustment for birth weight did not affect the effect estimates appreciably, whereas additional adjustment for body shape and weight until age 18, or current body mass index, attenuated the associations with both maternal and paternal smoking (rate ratio, 1.07; 95% CI, 0.98-1.16; and rate ratio, 1.06; 95% CI, 1.01-1.12, respectively). The associations of parental smoking during pregnancy with the risk of hypertension in the offspring were largely explained by body weight throughout life, suggesting that these associations may not reflect direct intrauterine mechanisms.

  4. Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

    PubMed

    Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

    2015-08-01

    Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high.

  5. [Membranous kidney diseases in adults].

    PubMed

    Sobarzo Toro, Martín; Vilches, Antonio

    2004-01-01

    Membranous nephropathy is the most common histologic phenotype associated with the primary nephrotic syndrome in adults and the second most common etiological diagnosis in over sixteen hundred renal biopsies on native kidneys processed at our institution over a 30 year period. Renal survival at 10 years is about 70%, but the course of the disease is related to a series of factors which have constituted the basis for mathematical models developed to predict the natural history in a given individual. These factors are gender, age, renal function at the time of diagnosis, presence of the nephrotic syndrome, high blood pressure and the degree of structural damage. Although in low risk patients a period of observation and the use of ACE inhibitors is a reasonable option, most nephrologists would elect to use pharmacological treatment to induce remissions of proteinuria and preserve renal function. The use of steroids and cytotoxic agents in alternating monthly cycles over six months is firmly supported by controlled, randomized clinical trials. If patients are resistant to this regimen or clinical considerations indicate it may be inappropriately toxic, the use of cyclosporin over 6 to 12 months is also a good choice, and it has been shown to be useful even in the context of deteriorating renal function. Mycophenolate mofetil and possibly rituximab may be options of last resort before considering the patient resistant to therapy. At all times, treatment of hypertension, non-specific antiproteinuric measures, and preventing complications of the nephrotic state should be top priorities in the overall therapeutic strategy.

  6. A test of the hypothesis that age at onset in Huntington disease is controlled by an X-linked recessive modifier.

    PubMed Central

    Ridley, R M; Farrer, L A; Frith, C D; Conneally, P M

    1992-01-01

    Data from the Research Roster for Huntington Disease Patients and Families were used to assess the hypothesis that juvenile onset in Huntington disease is determined by an X-linked recessive modifying gene in the affected parent. The observed proportion of affected fathers to affected mothers who had such offspring was not compatible with this hypothesis. Furthermore, neither the excess of affected grandfathers nor the existence of juvenile-onset and adult-onset cases within a sibship would be predicted by this model. We also rejected a more general hypothesis that a major change in gene expression across generations, measured by the presence of juvenile onset and/or major anticipation, is determined by an X-linked modifier. However, the inheritance of a propensity toward juvenile onset via the affected male line could be due to an abnormal pattern of paternal genomic imprinting. PMID:1531730

  7. Predicting abscesses in adults with community-onset monomicrobial Enterobacteriaceae bacteremia: microorganisms matters.

    PubMed

    Lee, Chung-Hsun; Lee, Ching-Chi; Hsieh, Chih-Chia; Hong, Ming-Yuan; Chi, Chih-Hsien

    2016-01-01

    Enterobacteriaceae is a leading pathogen of community-onset bacteremia. This study aims to establish a predictive scoring algorithm to identify adults with community-onset Enterobacteriaceae bacteremia who are at risk for abscesses. Of the total 1262 adults, 152 (12.0%) with abscess occurrence were noted. The 6 risk factors significantly associated with abscess occurrence-liver cirrhosis, diabetes mellitus, thrombocytopenia and high C-reactive protein (>100 mg/L) at bacteremic onset, delayed defervescence, and bacteremia-causing Klebsiella pneumoniae-were each assigned +1 point to form the scoring algorithm. In contrast, the elderly, fatal comorbidity (McCabe classification), and bacteremia-causing Escherichia coli were each assigned -1 point, owing to their negative associations with abscess occurrence. Using the proposed scoring algorithm, a cut-off value of +1 yielded a high sensitivity (85.5%) and an acceptable specificity (60.4%). Although the proposed predictive model needs further validation, this simple scoring algorithm may be useful for the early identification of abscesses by clinicians.

  8. The Onset of Depression During the Great Recession: Foreclosure and Older Adult Mental Health

    PubMed Central

    Cagney, Kathleen A.; Browning, Christopher R.; Iveniuk, James; English, Ned

    2014-01-01

    Objectives. We examined neighborhood-level foreclosure rates and their association with onset of depressive symptoms in older adults. Methods. We linked data from the National Social Life, Health, and Aging Project (2005–2006 and 2010–2011 waves), a longitudinal, nationally representative survey, to data on zip code–level foreclosure rates, and predicted the onset of depressive symptoms using logit-linked regression. Results. Multiple stages of the foreclosure process predicted the onset of depressive symptoms, with adjustment for demographic characteristics and changes in household assets, neighborhood poverty, and visible neighborhood disorder. A large increase in the number of notices of default (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.14, 2.67) and properties returning to ownership by the bank (OR = 1.62; 95% CI = 1.06, 2.47) were associated with depressive symptoms. A large increase in properties going to auction was suggestive of such an association (OR = 1.45; 95% CI = 0.96, 2.19). Age, fewer years of education, and functional limitations also were predictive. Conclusions. Increases in neighborhood-level foreclosure represent an important risk factor for depression in older adults. These results accord with previous studies suggesting that the effects of economic crises are typically first experienced through deficits in emotional well-being. PMID:24446830

  9. The Prevalence of Nonalcoholic Fatty Liver Disease and Related Metabolic Comorbidities Was Associated with Age at Onset of Moderate to Severe Plaque Psoriasis: A Cross-Sectional Study

    PubMed Central

    Gao, Yunlu; Ding, Yangfeng

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been found to be highly prevalent in psoriatic patients. Adult onset psoriasis could be divided into either early or late onset psoriasis. The associations between NAFLD and related metabolic comorbidities and age at onset of psoriasis have not yet been investigated. Our study was to evaluate the associations between prevalence of NAFLD and related metabolic conditions and early, late, and childhood onset psoriasis. A cross-sectional observational study was conducted on patients with moderate to severe plaque psoriasis. Data on clinical characteristics of NAFLD and related metabolic diseases (diabetes, hypertriglyceridemia, hyperuricemia, and metabolic syndrome) were collected. The prevalence of NAFLD in 439 patients (mean: 51±14 years, range: 18–85 years) was 55.8%. NAFLD was frequently identified in early onset patients (74.2%), and this diagnosis was particularly common in patients currently younger than 40 (85.3%). Diabetes was the least prevalent component of metabolic syndrome in early onset patients with metabolic syndrome but the most often found component in late onset ones. Patients with childhood onset psoriasis had the lowest frequencies of all metabolic comorbidities except hyperuricemia among the three groups. In the multivariate analyses, early onset was independently and positively associated with NAFLD, hypertriglyceridemia and hyperuricemia and independently and negatively associated with diabetes among early and late onset patients. The results suggested prevalence of NAFLD and related metabolic comorbidities was associated with age at onset of moderate to severe plaque psoriasis. Early onset of psoriasis was independently associated with greater odds of NAFLD, hypertriglyceridemia, hyperuricemia and smaller odds of diabetes compared to late onset. Early onset patients have metabolic syndrome mainly related to lipid disorders and abnormal glucose metabolism was not often involved. PMID:28099469

  10. Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease

    PubMed Central

    Steele, Andrew D.; Hutter, Gregor; Jackson, Walker S.; Heppner, Frank L.; Borkowski, Andrew W.; King, Oliver D.; Raymond, Gregory J.; Aguzzi, Adriano; Lindquist, Susan

    2008-01-01

    Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown. We hypothesized that the transcriptional regulator of the stress response, heat shock factor 1 (HSF1), would play an important role in prion disease. Uninoculated HSF1 knockout (KO) mice used in our study do not show signs of neurodegeneration as assessed by survival, motor performance, or histopathology. When inoculated with Rocky Mountain Laboratory (RML) prions HSF1 KO mice had a dramatically shortened lifespan, succumbing to disease ≈20% faster than controls. Surprisingly, both the onset of home-cage behavioral symptoms and pathological alterations occurred at a similar time in HSF1 KO and control mice. The accumulation of proteinase K (PK)-resistant PrP also occurred with similar kinetics and prion infectivity accrued at an equal or slower rate. Thus, HSF1 provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease. PMID:18757733

  11. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    ClinicalTrials.gov

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  12. Late-onset Pompe disease with complicated intracranial aneurysm: a Chinese case report

    PubMed Central

    Zhang, Bin; Zhao, Yuying; Liu, Junling; Li, Ling; Shan, Jingli; Zhao, Dandan; Yan, Chuanzhu

    2016-01-01

    Pompe disease is a rare autosomal recessive hereditary disease caused by genetic defects of acid maltase. This disease could be divided into two forms: infantile and late-onset, which mainly affect cardiac, respiratory, and skeletal muscle systems. Late-onset patients mainly show symptoms of skeletal muscle involvement, but recent reports have found that the central nervous system was also affected in some patients. Herein, we report a case of a female, adolescent-onset Pompe patient, who was diagnosed with complicated intracranial aneurysm in adulthood. PMID:27099502

  13. Parkinson disease in the elderly adult.

    PubMed

    Willis, Allison W

    2013-01-01

    Parkinson disease is the second most neurodegenerative disease, after Alzheimer disease, that affects up to two million Americans, the overwhelming majority of whom are aged 60 and older. The changing demographics of the country place more Americans at risk for Parkinson disease (PD) than ever before. Primary care physicians treat the majority of PD patients in the United States. Here I review diagnosis and treatment strategies for idiopathic Parkinson disease in the elderly adult.

  14. DHA supplementation for late onset Stargardt disease: NAT-3 study

    PubMed Central

    Querques, Giuseppe; Benlian, Pascale; Chanu, Bernard; Leveziel, Nicolas; Coscas, Gabriel; Soubrane, Gisele; Souied, Eric H

    2010-01-01

    Background: We analyzed the effects of a docosahexaenoic acid (DHA) supplementation in patients affected with late onset Stargardt disease (STGD). Methods: DHA (840 mg/day) was given to 20 STGD patients for six months. A complete ophthalmologic examination, including best-corrected visual acuity (BCVA) and multifocal electroretinogram (mfERG), was performed at inclusion day 0 (D0) and at month 6 (M6). Results: Overall, no statistical differences have been observed at M6 vs D0 as regards BCVA and mfERG (P > 0.05). Mild Improvement of BCVA and improvement of mfERG was noted in seven/40 eyes of four/20 patients. In the first patient, the peak of the a wave increased from 66 nV/deg2 to 75.4 nV/deg2 in the right eye (RE) and 24.5 nV/deg2 to 49.1 nV/deg2 in the left eye (LE). The peak of the b wave improved from 122 nV/deg2 to 157 nV/deg2 in the RE, and 102 nV/deg2 to 149 nV/deg2 in the LE. In the second patient peaks of the a and b waves respectively increased from 11.8 nV/deg2 to 72.1 nV/deg2 and 53 nV/deg2 to 185 nV/deg2 in the RE. In the third patient the peak of the a wave increased from 37 nV/deg2 to 43 nV/deg2 in the RE, and from 31 nV/deg2 to 45 nV/deg2 in the LE; the peak of the b wave improved from 70 nV/deg2 to 89 nV/deg2 in the RE, and from 101 nV/deg2 to 108 nV/deg2 in the LE. In the fourth patient, the peak of the a wave increased from 39 nV/deg2 to 42 nV/deg2 in the RE, and from 40 nV/deg2 to 43 nV/deg2 in the LE; the peak of the b wave improved from 86 nV/deg2 to 94 nV/deg2 in the RE, and from 87 nV/deg2 to 107 nV/deg2 in the LE. Conclusion: DHA seems to influence some functional parameters in patients affected with STGD. However, no short-term benefit should be expected from DHA supplementation. PMID:20668719

  15. Adult onset primary focal dystonia of the foot: an orthopaedic intervention.

    PubMed

    Logan, Loretta; Resseque, Barbara; Dontamsetti, Monica Sakshi

    2016-03-30

    A 54-year-old woman presented to a foot centre with a chief symptom of cramping in her toes, which, she believed, was of a secondary cause originating from a bunion. She was treated conservatively; however, she returned a month later as the symptoms had progressed to painful cramping of toes, toe-curling and instability while walking, due to involuntary movement of her toes. It was believed that the patient presented with a rare case of primary adult onset focal foot dystonia. This case report explains dystonia further in detail and delves into the different treatment and management options available today, including the unique orthopaedic intervention provided for this patient.

  16. Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

    PubMed

    Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James

    2017-02-01

    A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

  17. Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity.

    PubMed

    Farrer, L A; Myers, R H; Cupples, L A; St George-Hyslop, P H; Bird, T D; Rossor, M N; Mullan, M J; Polinsky, R; Nee, L; Heston, L

    1990-03-01

    We evaluated age at onset and lifetime risk for Alzheimer's disease (AD) in 70 kindreds with familial AD (designated FAD) composed of 541 affected and 1,066 unaffected offspring of demented parents who were identified retrospectively. Using a survival analysis method which takes into account affected persons with unknown onset ages and unaffected persons with unknown censoring ages, we found lifetime risk of AD among at-risk offspring by age 87 to be 64%. Analysis of age at onset among kindreds showed evidence for a bimodal distribution: in this sample, families with a mean onset age of less than 58 years were designated as having early-onset, while late-onset families had a mean onset age greater than 58 years. At-risk offspring in early-onset families had an estimated lifetime risk for dementia of 53%, which is significantly less than the risk of 86% that was estimated for offspring in late-onset families. Men and women in early-onset families had equivalent risk of dementia. In late-onset families, the risk to female offspring was somewhat higher than to male offspring but this difference was marginally significant. Lifetime risk of dementia in early-onset FAD kindreds is consistent with an autosomal dominant inheritance model. Our results may suggest that late-onset FAD has at least 2 etiologies; AD in some families may be transmitted as a dominant trait, whereas a proportion of cases in these and other late-onset families may be caused by other genetic or shared environmental factors.

  18. Chronic obstructive pulmonary disease - adults - discharge

    MedlinePlus

    ... visit when they're all better. Save Your Energy at Home Place items you use often in ... or the skin around your fingernails are blue Alternative Names COPD - adults - discharge; Chronic obstructive airways disease - ...

  19. Tumor diagnosis preceding Alzheimer's disease onset: is there a link between cancer and Alzheimer's disease?

    PubMed

    Realmuto, Sabrina; Cinturino, Antonio; Arnao, Valentina; Mazzola, Maria Antonietta; Cupidi, Chiara; Aridon, Paolo; Ragonese, Paolo; Savettieri, Giovanni; D'Amelio, Marco

    2012-01-01

    Studies reporting an inverse association between Alzheimer's disease (AD) and cancer are scant. Available data are mostly based on ancillary findings of mortality data or obtained from studies evaluating frequency of neoplasms in AD patients independently if they occurred before or after AD. Moreover, some studies estimated frequencies of neoplasms in demented individuals, who were not necessarily AD patients. We estimated frequency of tumors preceding the onset of AD in AD patients and compared it to that of age- and gender-matched AD-free individuals. Occurrence of tumors preceding AD onset was assessed through a semi-structured questionnaire. Tumors were categorized as benign, malignant, or of uncertain classification and as endocrine-related or not. Odds ratios (OR), used as measure of the association between the two diseases, were adjusted for tumor categories and known risk factors for AD and tumors. We included 126 AD patients and 252 matched controls. Tumor frequency before AD onset was 18.2% among cases and 24.2% among controls. There was a suggestive trend of an overall inverse association between the two diseases (adjusted OR 0.6; 95% CI 0.4-1.1; p = 0.11). Risk for neoplasms was significantly reduced only for women (adjusted OR, 0.5; 95% CI 0.3-0.9; p = 0.03) and for endocrine related tumors (adjusted OR, 0.5; 95% CI 0.2-1; p = 0.04). Our study confirms the inverse association reported in previous epidemiological studies. Though our findings might be explained by processes playing an opposite role in tumors development and neurodegeneration, they are also suggestive for a possible role of estrogen.

  20. Gross lesions of alimentary disease in adult cattle.

    PubMed

    Njaa, Bradley L; Panciera, Roger J; Clark, Edward G; Lamm, Catherine G

    2012-11-01

    The purpose of the gross necropsy examination of the gastrointestinal tract is to recognize the presence of lesions, thus requiring a basic understanding of its normal appearance and anatomy. This article highlights gross changes to the gastrointestinal tract of adult cattle that help place the disease processes into broad categories. Although few gross lesions reach the zenith of pathognomonic, there are numerous lesions that, when considered in aggregate with history (eg, number of animals affected, environment, duration of signs, time of onset relative to management changes, previous management) and clinical signs, can help narrow the spectrum of causes, provide a basis for a strong presumptive diagnosis, and focus diagnostic test selection.

  1. Ethnicity and Onset of Cardiovascular Disease: A CALIBER Study

    ClinicalTrials.gov

    2016-05-11

    Abdominal Aortic Aneurysm; Coronary Heart Disease; Sudden Cardiac Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest

  2. Motor and non-motor symptoms in old-age onset Parkinson's disease patients.

    PubMed

    Mendonça, Marcelo D; Lampreia, Tania; Miguel, Rita; Caetano, André; Barbosa, Raquel; Bugalho, Paulo

    2017-03-17

    Advancing age is a well-known risk factor for Parkinson's disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.

  3. Adult onset leukodystrophy with neuroaxonal spheroids and demyelinating plaque-like lesions.

    PubMed

    Martinez-Saez, Elena; Shah, Sachit; Costa, Carme; Fleminger, Simon; Connor, Stephen; Bodi, Istvan

    2012-06-01

    Adult onset leukodystrophy with neuroaxonal spheroids is an uncommon cause of dementia. Both hereditary (autosomal dominant) and sporadic cases have been described. A 41-year-old African woman presented with inappropriate behavior and personality change consistent with frontal lobe dysfunction. MRI demonstrated diffuse frontoparietal white matter signal abnormality and volume loss, as well as focal enhancing white matter lesions, while CT scan showed white matter calcifications. She had been gradually deteriorating over the last 5 years, diagnosed as having progressive demyelinating illness. She died of recurrent chest infections. There was no familial history. The brain showed prominent symmetrical white matter changes with greyish discolorization mainly affecting the frontal and parietal lobes, with less involvement of the temporal lobe and only mildly affecting the occipital white matter. Histology revealed deep white matter atrophy with many neuroaxonal spheroids labelled by neurofilament and β-amyloid precursor protein. In addition, scattered inactive demyelinating plaque-like lesions were found in the periventricular areas, brainstem and the cervical spinal cord. This case had typical features of an adult onset leukodystrophy with neuroaxonal spheroids. However, we also demonstrated demyelinating plaque-like lesions, which has not been previously described. The possibility of a demyelinating origin contributing to the changes may be considered in the pathogenesis of this condition.

  4. Fat and carbohydrate metabolism during exercise in late-onset Pompe disease.

    PubMed

    Preisler, Nicolai; Laforet, Pascal; Madsen, Karen Lindhardt; Hansen, Regitze Sølling; Lukacs, Zoltan; Ørngreen, Mette Cathrine; Lacour, Arnaud; Vissing, John

    2012-11-01

    Pompe disease is caused by absence of the lysosomal enzyme acid alpha-glucosidase. It is generally assumed that intra-lysosomal hydrolysis of glycogen does not contribute to skeletal muscle energy production during exercise. However, this hypothesis has never been tested in vivo during exercise. We examined the metabolic response to exercise in patients with late-onset Pompe disease, in order to determine if a defect in energy metabolism may play a role in the pathogenesis of Pompe disease. We studied six adult patients with Pompe disease and 10 healthy subjects. The participants underwent ischemic forearm exercise testing, and peak work capacity was determined. Fat and carbohydrate metabolism during cycle exercise was examined with a combination of indirect calorimetry and stable isotope methodology. Finally, the effects of an IV glucose infusion on heart rate, ratings of perceived exertion, and work capacity during exercise were determined. We found that peak oxidative capacity was reduced in the patients to 17.6 vs. 38.8 ml kg(-1) min(-1) in healthy subjects (p = 0.002). There were no differences in the rate of appearance and rate of oxidation of palmitate, or total fat and carbohydrate oxidation, between the patients and the healthy subjects. None of the subjects improved exercise tolerance by IV glucose infusion. In conclusion, peak oxidative capacity is reduced in Pompe disease. However, skeletal muscle fat and carbohydrate use during exercise was normal. The results indicate that a reduced exercise capacity is caused by muscle weakness and wasting, rather than by an impaired skeletal muscle glycogenolytic capacity. Thus, it appears that acid alpha-glucosidase does not play a significant role in the production of energy in skeletal muscle during exercise.

  5. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

    SciTech Connect

    Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

    1989-06-01

    No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect.

  6. Sensorimotor Oscillations Prior to Speech Onset Reflect Altered Motor Networks in Adults Who Stutter

    PubMed Central

    Mersov, Anna-Maria; Jobst, Cecilia; Cheyne, Douglas O.; De Nil, Luc

    2016-01-01

    Adults who stutter (AWS) have demonstrated atypical coordination of motor and sensory regions during speech production. Yet little is known of the speech-motor network in AWS in the brief time window preceding audible speech onset. The purpose of the current study was to characterize neural oscillations in the speech-motor network during preparation for and execution of overt speech production in AWS using magnetoencephalography (MEG). Twelve AWS and 12 age-matched controls were presented with 220 words, each word embedded in a carrier phrase. Controls were presented with the same word list as their matched AWS participant. Neural oscillatory activity was localized using minimum-variance beamforming during two time periods of interest: speech preparation (prior to speech onset) and speech execution (following speech onset). Compared to controls, AWS showed stronger beta (15–25 Hz) suppression in the speech preparation stage, followed by stronger beta synchronization in the bilateral mouth motor cortex. AWS also recruited the right mouth motor cortex significantly earlier in the speech preparation stage compared to controls. Exaggerated motor preparation is discussed in the context of reduced coordination in the speech-motor network of AWS. It is further proposed that exaggerated beta synchronization may reflect a more strongly inhibited motor system that requires a stronger beta suppression to disengage prior to speech initiation. These novel findings highlight critical differences in the speech-motor network of AWS that occur prior to speech onset and emphasize the need to investigate further the speech-motor assembly in the stuttering population. PMID:27642279

  7. [Alarming signs and symptoms in the early diagnostics of late onset Pompe disease: super omnia clinica].

    PubMed

    Nikitin, S S; Kurbatov, S A; Bredelev, V A; Kovalchuk, M O

    2015-01-01

    Pompe disease (PD) is a rare autosomal recessive muscle lysosomal glycogenosis caused by a deficiency of acid-α-glucosidase. There are two main forms of the disease: aggressive infantile PD started within the first year of life with a severe enzyme deficiency and multiorgan involvement, and late onset PD (LOPD) with progressive signs and symptoms including predominant proximal, axial muscle weakness and respiratory insufficiency started at any time from 1 till 75 years and older. Usually due to physician's unawareness, most adults with PD are diagnosed with great delay. The typical features and early nonspecific signs in four patients, aged between 35 and 72 years, with confirmed LOPD are delineated and discussed in correspondence with the age of first signs, age development of muscle weakness, distribution and age of final diagnosis. The disorders for differential diagnosis and spectrum of conditions that expanded the possibility of PB are listed. The fluorometrically analyzed level of acid α-glucosidase from dried blood spots is considered to be the first choice diagnostic method for clinically suspected cases of LOPD.

  8. Reverse cascade screening of newborns for hereditary haemochromatosis: a model for other late onset diseases?

    PubMed Central

    Cadet, E; Capron, D; Gallet, M; Omanga-Leke, M; Boutignon, H; Julier, C; Robson, K; Rochette, J

    2005-01-01

    detecting affected adults with undiagnosed haemochromatosis. This strategy allows almost complete coverage for HH and could be a model for efficient screening for other late onset genetic diseases. PMID:15863667

  9. Occupational exposures and uncontrolled adult-onset asthma in the European Community Respiratory Health Survey II.

    PubMed

    Le Moual, Nicole; Carsin, Anne-Elie; Siroux, Valérie; Radon, Katja; Norback, Dan; Torén, Kjell; Olivieri, Mario; Urrutia, Isabel; Cazzoletti, Lucia; Jacquemin, Bénédicte; Benke, Geza; Kromhout, Hans; Mirabelli, Maria C; Mehta, Amar J; Schlünssen, Vivi; Sigsgaard, Torben; Blanc, Paul D; Kogevinas, Manolis; Antó, Josep M; Zock, Jan-Paul

    2014-02-01

    Occupational exposure is a well-recognised modifiable risk factor for asthma, but the relationship between occupational exposure and asthma control has not been studied. We aimed to study this association among working-age adults from the European Community Respiratory Health Survey (ECRHS). Data were available for 7077 participants (mean age 43 years, 45% never-smokers, 5867 without asthma and 1210 with current asthma). Associations between occupational exposure to specific asthmagens and asthma control status (33% with uncontrolled asthma, based on the Global Initiative for Asthma guidelines) were evaluated using logistic and multinomial regressions, adjusted for age, sex and smoking status, with study areas included as a random effect. Statistically significant positive associations were observed between uncontrolled adult-onset asthma and both past 12-month and 10-year exposure to any occupational asthmagens (OR (95% CI) 1.6 (1.0-2.40) and 1.7 (1.2-2.5), respectively); high (1.7 (1.0-2.8) and 1.9 (1.3-2.9), respectively) and low (1.6 (1.0-2.7) and 1.8 (1.2-2.7), respectively) molecular weight agents; and cleaning agents (2.0 (1.1-3.6) and 2.3 (1.4-3.6), respectively), with stronger associations for long-term exposures. These associations were mainly explained by the exacerbation domain of asthma control and no associations were observed between asthmagens and partly controlled asthma. These findings suggest that occupational exposure to asthmagens is associated with uncontrolled adult-onset asthma. Occupational risk factors should be quickly identified to prevent uncontrolled asthma.

  10. An inducible mouse model of late onset Tay-Sachs disease.

    PubMed

    Jeyakumar, Mylvaganam; Smith, David; Eliott-Smith, Elena; Cortina-Borja, Mario; Reinkensmeier, Gabriele; Butters, Terry D; Lemm, Thorsten; Sandhoff, Konrad; Perry, V Hugh; Dwek, Raymond A; Platt, Frances M

    2002-08-01

    Mouse models of the G(M2) gangliosidoses, Tay-Sachs and Sandhoff disease, are null for the hexosaminidase alpha and beta subunits respectively. The Sandhoff (Hexb-/-) mouse has severe neurological disease and mimics the human infantile onset variant. However, the Tay-Sachs (Hexa-/-) mouse model lacks an overt phenotype as mice can partially bypass the blocked catabolic pathway and escape disease. We have investigated whether a subset of Tay-Sachs mice develop late onset disease. We have found that approximately 65% of the mice develop one or more clinical signs of the disease within their natural life span (n = 52, P < 0.0001). However, 100% of female mice with repeat breeding histories developed late onset disease at an earlier age (n = 21, P < 0.0001) and displayed all clinical features. Repeat breeding of a large cohort of female Tay-Sachs mice confirmed that pregnancy induces late onset Tay-Sachs disease. Onset of symptoms correlated with reduced up-regulation of hexosaminidase B, a component of the bypass pathway.

  11. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

    PubMed Central

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

  12. Prevention of Early-onset Neonatal Group B Streptococcal Disease

    PubMed Central

    Marió, M. J. Soto; Valenzuela, I; Vásquez, A. E; Illanes, S. E

    2013-01-01

    Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is an opportunistic pathogen that colonizes the gastrointestinal and genitourinary tracts of up to 50% of healthy adults and newborns; it is responsible for significant morbidity and mortality. Early detection can be used to establish the use of antibiotic prophylaxis to significantly reduce neonatal sepsis. This article reviews methods of detection and prevention of GBS infection in the neonate. PMID:24358406

  13. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q

    SciTech Connect

    Morissette, J.; Plante, M.; Raymond, V.

    1995-06-01

    Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members >35 years of age, except for three obligatory carriers. Key combination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years. 49 refs., 4 figs., 2 tabs.

  14. [Evaluation of congenital heart disease in adults].

    PubMed

    Oliver Ruiz, José María; Mateos García, Marta; Bret Zurita, Montserrat

    2003-06-01

    Improvements in the diagnosis and surgical treatment of congenital heart disease during infancy and childhood have resulted in an outstanding increase in the prevalence of these entities during adulthood. Congenital heart disease in the adult represents a new diagnostic challenge to the consultant cardiologist, unfamiliar with the anatomical and functional complexities of cardiac malformations. Assessment of adult congenital heart disease with imaging techniques can be as accurate as in children. However, these techniques cannot substitute for a detailed clinical assessment. Physical examination, electrocardiography and chest x-rays remain the three main pillars of bedside diagnosis. Transthoracic echocardiography is undoubtedly the imaging technique which provides most information, and in many situations no additional studies are needed. Nevertheless, ultrasound imaging properties in adults are not as favorable as in children, and prior surgical procedures further impair image quality. Despite recent advances in ultrasound technologies such as harmonic or contrast imaging, other diagnostic procedures are sometimes required. Fortunately, transesophageal echocardiography and magnetic resonance imaging are easily performed in the adult, and do not require anaesthetic support, in contrast to pediatric patients. These techniques, together with nuclear cardiology and cardiac catheterization, complete the second tier of diagnostic techniques for congenital heart disease. To avoid unnecessary repetition of diagnostic procedures, the attending cardiologist should choose the sequence of diagnostic techniques carefully; although the information this yields is often redundant, it is also frequently complementary. This article aims to compare the diagnostic utility of different imaging techniques in adult patients with congenital heart disease, both with and without prior surgical repair.

  15. Fahr's Disease Presenting with Dementia at Onset: A Case Report and Literature Review

    PubMed Central

    Calabrò, Rocco Salvatore; Spadaro, Letteria; Marra, Angela; Bramanti, Placido

    2014-01-01

    Fahr's disease (FD) is characterized by sporadic or familiar idiopathic calcification of the basal ganglia, dentate nuclei of the cerebellum, and centrum semiovale, mainly presenting with movement disorder, dementia, and behavioral abnormalities. We described a rare case of Fahr's disease presenting at onset only with behavioral and neuropsychological alterations, whose diagnosis was supposed only after a brain CT, which showed extensive bilateral calcifications in the dentate nuclei of the cerebellum and basal ganglia. Since the onset of Fahr's disease may be a dysexecutive syndrome with behavioral abnormalities, the clinical and radiological features are really important to do the appropriate diagnosis. PMID:24803731

  16. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    PubMed

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age.

  17. Late onset parkinsonian syndrome in Hallervorden-Spatz disease.

    PubMed Central

    Alberca, R; Rafel, E; Chinchon, I; Vadillo, J; Navarro, A

    1987-01-01

    Two siblings, from consanguineous parents, developed in their twenties a Parkinsonian syndrome. In the elder, the disease evolved for 13 years and the necropsic study was diagnostic of Hallervorden-Spatz disease. The younger sibling is severely affected after 12 years of the disorder. Several CT and one MR studies done in this patient during the last 4 years have been normal. Ultrastructural studies of the bone marrow histiocytes and blood lymphocytes disclosed peculiar inclusions. Bromocriptine in low doses proved to be a beneficial therapy for this patient. Images PMID:3437298

  18. Duration of illness in Huntington's disease is not related to age at onset.

    PubMed

    Roos, R A; Hermans, J; Vegter-van der Vlis, M; van Ommen, G J; Bruyn, G W

    1993-01-01

    The age at onset and duration of illness were studied in patients with Huntington's disease in the Leiden Roster which at 1 July 1990 contained 2787 patients. Of 1106 patients, 800 deceased and 306 alive, the age at onset was known. The median duration was 16.2 (range 2-45) years. In contrast to the current opinion, the median duration was independent of the age of onset. The median duration in juvenile Huntington's disease was 17.1 years, which is much longer than reported in the literature, and comparable with the categories for the age of onset of 20-34 and 35-49 years. Only in the group where onset was over 50 years of age was the median duration somewhat shorter (15.6 years), which can be ascribed to unrelated causes of death. As age of onset and duration of illness are not related, at least two mechanisms to determine the clinical course have to be postulated: one for age of onset and another for duration of illness. Duration was shorter for males, especially for those with an affected father.

  19. Duration of illness in Huntington's disease is not related to age at onset.

    PubMed Central

    Roos, R A; Hermans, J; Vegter-van der Vlis, M; van Ommen, G J; Bruyn, G W

    1993-01-01

    The age at onset and duration of illness were studied in patients with Huntington's disease in the Leiden Roster which at 1 July 1990 contained 2787 patients. Of 1106 patients, 800 deceased and 306 alive, the age at onset was known. The median duration was 16.2 (range 2-45) years. In contrast to the current opinion, the median duration was independent of the age of onset. The median duration in juvenile Huntington's disease was 17.1 years, which is much longer than reported in the literature, and comparable with the categories for the age of onset of 20-34 and 35-49 years. Only in the group where onset was over 50 years of age was the median duration somewhat shorter (15.6 years), which can be ascribed to unrelated causes of death. As age of onset and duration of illness are not related, at least two mechanisms to determine the clinical course have to be postulated: one for age of onset and another for duration of illness. Duration was shorter for males, especially for those with an affected father. PMID:8429330

  20. Juvenile onset spondyloarthropathies: therapeutic aspects

    PubMed Central

    Burgos-Vargas, R

    2002-01-01

    Juvenile onset spondyloarthropathy (SpA) is a term that refers to a group of human leucocyte antigen (HLA)-B27 associated inflammatory disorders affecting children under the age of 16 years, producing a continuum of clinical symptoms through adulthood. This disease is characterised by enthesopathy and arthropathy affecting the joints of the lower extremities and seronegativity for IgM rheumatoid factor and antinuclear antibodies. Children usually present with undifferentiated SpA and progress to differentiated forms over time. Except for the prevalence of some clinical features at onset, the pathogenic and clinical aspects of juvenile onset SpAs resemble those of the adult disease. Thus application of the same or similar therapeutic measures for both juvenile and adult onset SpAs seems logical. Current treatments for juvenile onset SpA provide symptomatic improvement, but do not alter disease progression. The increased expression of tumour necrosis factor alpha (TNFα) in synovial tissue of patients with adult and juvenile onset SpA and its correlation with infiltration of inflammatory mediators into the synovia suggest a significant pathogenic role of this cytokine. Clinical trials of anti-TNFα antibody (infliximab) therapy in patients with adult onset SpA have demonstrated significant clinical improvement in inflammatory pain, function, disease activity, and quality of life in correlation with histological and immunohistochemical evidence of modulation of synovial inflammatory processes. These promising findings suggest that anti-TNFα therapy may confer similar benefits in patients with juvenile onset SpA. PMID:12381509

  1. [A case of adult-onset type II citrullinemia in an elderly patient].

    PubMed

    Kitaoka, Mayuko; Sakaeda, Hiroshi; Suzuki, Mika; Miki, Toshifumi; Saito, Junko; Chikamori, Masayasu; Tomita, Hideharu; Ichikawa, Hiromoto; Yoshimoto, Kaori; Takamatsu, Masahiro; Okada, Mitsuo; Aono, Rei; Enzan, Hideaki; Miyamoto, Takako

    2013-03-01

    A 72-year-old man presented with consciousness disturbance. The results of brain magnetic resonance imaging and cerebrospinal fluid examination were normal, but triphasic waves were noted on electroencephalography. His plasma ammonia level was elevated due to which encephalopathy secondary to hyperammonemia was suspected. However, his liver function was normal, and no evidence of cirrhosis or portal-systemic shunt was noted. The patient's medical history revealed that he had a tendency to excessively consume pulse products since childhood, and an amino acid analysis showed elevation of citrulline and arginine levels. Thus, we diagnosed the patient with an extremely rare case of adult-onset type II citrullinemia, which was triggered by cessation of the intake of pulse foods (soybeans and peanuts) due to dental problems.

  2. Adult-onset intradural spinal teratoma in the lumbar spine: A case report.

    PubMed

    Arai, Yasuhisa; Takahashi, Masaki; Takeda, Koutarou; Shitoto, Katsuo

    2000-12-01

    Intradural spinal teratoma is a very rare tumour that can be associated with dysraphic defects. We report a case of adult-onset intradural spinal teratoma in the lumbar spine. The patient was a 54-year-old female who had chief complaints of a gait disturbance. X-rays showed an enlargement of the interpedicular distance at L3/L4 and spina bifida distal to L4. MRI showed a spindle-shaped tumour between L2 and L5. We performed laminotomy using an ultrasonic surgical knife. Pathological diagnosis of the resected tumour was matured teratoma. The diagnosis of matured teratoma was made because the tumour had no epithelium and a layered structure including prostate tissue, matured fat, cartilage and sweat gland.

  3. Acute-onset unilateral psychogenic hearing loss in adults: report of six cases and diagnostic pitfalls.

    PubMed

    Oishi, Naoki; Kanzaki, Sho; Kataoka, Chinatsu; Tazoe, Mami; Takei, Yasuhiko; Nagai, Keiichi; Kohno, Naoyuki; Ogawa, Kaoru

    2009-01-01

    We encountered 6 rare cases of acute-onset unilateral psychogenic hearing loss in adults. All were women in their 20s and 30s. Three cases had severe hearing impairment characterized by hearing loss at every frequency; 2 cases had profound hearing impairment, and 1 case had low-frequency hearing impairment. Of the 6 cases, 3 had a history of hearing loss, and 1 had a history of psychogenic visual disturbance. All 6 cases were initially diagnosed as having idiopathic sudden sensorineural hearing loss; all subsequently received steroid therapy. Three cases were not diagnosed as being psychogenic in origin until otoacoustic emissions and auditory brain responses were performed. Although the presence of distinctive clinical features (age, gender, and past history) is important for suspecting psychogenic hearing loss, objective audiological tests such as otoacoustic emissions are essential for diagnosing some cases. Compared to the existing reports of similar cases, our cases had a poorer prognosis (only 2 cases were cured).

  4. Childhood attachment, childhood sexual abuse, and onset of masturbation among adult sexual offenders.

    PubMed

    Smallbone, Stephen W; McCabe, Billee-Anne

    2003-01-01

    Written autobiographies of 48 incarcerated adult male sexual offenders (22 rapists, 13 intrafamilial child molesters, and 13 extrafamilial child molesters) were used to generate retrospective self-report measures of their childhood maternal and paternal attachment, childhood sexual abuse experiences, and onset of masturbation. Contrary to expectation, the offenders as a combined group more often reported secure than they did insecure childhood maternal and paternal attachment. There were no differences between the three offender subgroups with respect to maternal attachment; however the rapists and the intrafamilial child molesters were more likely to report insecure paternal attachment than were the extrafamilial child molesters. There were no differences between these offender subgroups in the frequency with which childhood sexual abuse was reported. However, offenders with insecure paternal attachment were more likely to report having been sexually abused than were those with secure paternal attachment. Sexually abused offenders in turn reported earlier onset of masturbation than did those who were not sexually abused. These results are consistent with contemporary attachment models linking insecure childhood attachment to childhood sexual abuse, and with traditional conditioning models linking childhood sexual abuse, early masturbation, and sexual offending.

  5. Delayed Onset Muscle Soreness After Inspiratory Threshold Loading in Healthy Adults

    PubMed Central

    Mathur, Sunita; Sheel, A. William; Road, Jeremy D.; Reid, W. Darlene

    2010-01-01

    Purpose: Skeletal muscle damage occurs following high-intensity or unaccustomed exercise; however, it is difficult to monitor damage to the respiratory muscles, particularly in humans. The aim of this study was to use clinical measures to investigate the presence of skeletal muscle damage in the inspiratory muscles. Methods: Ten healthy subjects underwent 60 minutes of voluntary inspiratory threshold loading (ITL) at 70% of maximal inspiratory pressure. Maximal inspiratory and expiratory mouth pressures, delayed onset muscle soreness on a visual analogue scale and plasma creatine kinase were measured prior to ITL, and at repeated time points after ITL (4, 24 and 48 hours post-ITL). Results: Delayed onset muscle soreness was present in all subjects 24 hours following ITL (intensity = 22 ± 6 mm; significantly higher than baseline p = 0.02). Muscle soreness was reported primarily in the anterior neck region, and was correlated to the amount of work done by the inspiratory muscles during ITL (r = 0.72, p = 0.02). However, no significant change was observed in maximal inspiratory or expiratory pressures or creatine kinase. Conclusions: These findings suggest that an intense bout of ITL results in muscle soreness primarily in the accessory muscles of inspiration, however, may be insufficient to cause significant muscle damage in healthy adults. PMID:20467514

  6. Adult-onset NREM parasomnia with hypnopompic hallucinatory pain: a case report.

    PubMed

    Mantoan, Laura; Eriksson, Sofia H; Nisbet, Angus P; Walker, Matthew C

    2013-02-01

    We report the case of a 43-year-old woman presenting with nocturnal episodes of pain and screaming during sleep starting at age 30. There was no childhood or family history of parasomnia. The events had gradually become more frequent over the years, occurring in the first half of the night within 2 h of sleep onset. There were no triggers, and she had partial amnesia for the events. A diagnosis of adult-onset sleep terrors was made on clinical grounds and supported polysomnographically. Seizures and periodic limb movements were excluded as triggering factors. There was some mild sleep disordered breathing (predominantly non-desaturating hypopnea with a propensity for REM sleep of debatable significance). Imaging of the brain and spine and neurophysiological investigations ruled out lesions, entrapments, or neuropathies as possible causes of pain. Treatment (clonazepam, paroxetine, or gabapentin) was poorly tolerated and made no difference to the nocturnal episodes, while trazodone worsened them. This is the first report of hypnopompic psychic pain in association with a NREM parasomnia. We hypothesize that the pain may represent a sensory hallucination analogous to the more commonly recognized visual NREM parasomnia-associated hypnopompic visual hallucinations and that, as such, it may arise during arousal of the sensory neocortex as confabulatory response.

  7. Climate change influences on the annual onset of Lyme disease in the United States.

    PubMed

    Monaghan, Andrew J; Moore, Sean M; Sampson, Kevin M; Beard, Charles B; Eisen, Rebecca J

    2015-07-01

    Lyme disease is the most commonly reported vector-borne illness in the United States. Lyme disease occurrence is highly seasonal and the annual springtime onset of cases is modulated by meteorological conditions in preceding months. A meteorological-based empirical model for Lyme disease onset week in the United States is driven with downscaled simulations from five global climate models and four greenhouse gas emissions scenarios to project the impacts of 21st century climate change on the annual onset week of Lyme disease. Projections are made individually and collectively for the 12 eastern States where >90% of cases occur. The national average annual onset week of Lyme disease is projected to become 0.4-0.5 weeks earlier for 2025-2040 (p<0.05), and 0.7-1.9 weeks earlier for 2065-2080 (p<0.01), with the largest shifts for scenarios with the highest greenhouse gas emissions. The more southerly mid-Atlantic States exhibit larger shifts (1.0-3.5 weeks) compared to the Northeastern and upper Midwestern States (0.2-2.3 weeks) by 2065-2080. Winter and spring temperature increases primarily cause the earlier onset. Greater spring precipitation and changes in humidity partially counteract the temperature effects. The model does not account for the possibility that abrupt shifts in the life cycle of Ixodes scapularis, the primary vector of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, may alter the disease transmission cycle in unforeseen ways. The results suggest 21st century climate change will make environmental conditions suitable for earlier annual onset of Lyme disease cases in the United States with possible implications for the timing of public health interventions.

  8. Climate change influences on the annual onset of Lyme disease in the United States

    PubMed Central

    Monaghan, Andrew J.; Moore, Sean M.; Sampson, Kevin M.; Beard, Charles B.; Eisen, Rebecca J.

    2015-01-01

    Lyme disease is the most commonly reported vector-borne illness in the United States. Lyme disease occurrence is highly seasonal and the annual springtime onset of cases is modulated by meteorological conditions in preceding months. A meteorological-based empirical model for Lyme disease onset week in the United States is driven with downscaled simulations from five global climate models and four greenhouse gas emissions scenarios to project the impacts of 21st century climate change on the annual onset week of Lyme disease. Projections are made individually and collectively for the 12 eastern States where >90% of cases occur. The national average annual onset week of Lyme disease is projected to become 0.4–0.5 weeks earlier for 2025–2040 (p < 0.05), and 0.7–1.9 weeks earlier for 2065–2080 (p < 0.01), with the largest shifts for scenarios with the highest greenhouse gas emissions. The more southerly mid-Atlantic States exhibit larger shifts (1.0–3.5 weeks) compared to the Northeastern and upper Midwestern States (0.2–2.3 weeks) by 2065–2080. Winter and spring temperature increases primarily cause the earlier onset. Greater spring precipitation and changes in humidity partially counteract the temperature effects. The model does not account for the possibility that abrupt shifts in the life cycle of Ixodes scapularis, the primary vector of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, may alter the disease transmission cycle in unforeseen ways. The results suggest 21st century climate change will make environmental conditions suitable for earlier annual onset of Lyme disease cases in the United States with possible implications for the timing of public health interventions. PMID:26025268

  9. Climate change influences on the annual onset of Lyme disease in the United States

    NASA Astrophysics Data System (ADS)

    Monaghan, A. J.; Moore, S. M.; Sampson, K. M.; Beard, C. B.; Eisen, R. J.

    2015-12-01

    Lyme disease is the most commonly reported vector-borne illness in the United States. Lyme disease occurrence is highly seasonal and the annual springtime onset of cases is modulated by meteorological conditions in preceding months. A meteorological-based empirical model for Lyme disease onset week in the United States is driven with downscaled simulations from five global climate models and four greenhouse gas emissions scenarios to project the impacts of 21st century climate change on the annual onset week of Lyme disease. Projections are made individually and collectively for the 12 eastern States where >90% of cases occur. The national average annual onset week of Lyme disease is projected to become 0.4-0.5 weeks earlier for 2025-2040 (p<0.05), and 0.7-1.9 weeks earlier for 2065-2080 (p<0.01), with the largest shifts for scenarios with the highest greenhouse gas emissions. The more southerly mid-Atlantic States exhibit larger shifts (1.0-3.5 weeks) compared to the Northeastern and upper Midwestern States (0.2-2.3 weeks) by 2065-2080. Winter and spring temperature increases primarily cause the earlier onset. Greater spring precipitation and changes in humidity partially counteract the temperature effects. The model does not account for the possibility that abrupt shifts in the life cycle of Ixodes scapularis, the primary vector of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, may alter the disease transmission cycle in unforeseen ways. The results suggest 21st century climate change will make environmental conditions suitable for earlier annual onset of Lyme disease cases in the United States with possible implications for the timing of public health interventions.

  10. Early life exposures and the occurrence and timing of heart disease among the older adult Puerto Rican population.

    PubMed

    McEnry, Mry; Palloni, Alberto

    2010-02-01

    Few studies have examined the effects of early life conditions on the timing of the onset of heart disease. We use the remarkable example of a representative sample of the population of older Puerto Ricans aged 60-74 who lived in the countryside during childhood (n = 1,438) to examine the effects ofseasonal exposures to poor nutrition and infectious diseases during late gestation on the timing of the onset and the probability of ever experiencing adult heart disease. Cox and log logistic hazard models controlling for childhood conditions (self-reported childhood health status and socioeconomic status [SES], rheumatic fever, and knee height) and adult risk factors (adult SES, obesity, smoking, exercise, and self-reported diabetes) showed that the risk of onset of heart disease was 65% higher among those born during high-exposure periods compared with unexposed individuals. However, there were no significant differences in median time of onset for those ever experiencing heart disease. As a comparison, we found that there were no significant seasonality effects for those who lived in urban areas during childhood. We conclude that early exposures in utero have important ramifications for adult heart disease among the older Puerto Rican population. We show, however, that while exposure is associated with the probability of ever experiencing adult heart disease, it is not associated with the timing of onset among those who do experience it.

  11. Early-onset psychoses: comparison of clinical features and adult outcome in 3 diagnostic groups.

    PubMed

    Ledda, Maria Giuseppina; Fratta, Anna Lisa; Pintor, Manuela; Zuddas, Alessandro; Cianchetti, Carlo

    2009-09-01

    A comparison of clinical features and adult outcome in adolescents with three types of psychotic disorders: schizophrenic (SPh), schizoaffective (SA) and bipolar with psychotic features (BPP). Subjects (n = 41) were finally diagnosed (DSM-IV criteria) with SPh (n = 17), SA (n = 11) or BPP (n = 13). Clinical evaluation took place at onset and at a 3-year follow-up in all 41, and at least after 5 years in 36 patients. Symptoms were rated on the basis of the Positive and Negative Syndrome Scale (PANSS), integrating items from the Brief Psychiatric Rating Scale (BPRS) and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). The Children Global Assessment Scale (C-GAS) and the Global Assessment Scale (GAF) were used to evaluate global functioning. Significant differences in clinical features were found in the three diagnostic groups as regards several parameters, some present on one and not on other rating scales, underscoring the insufficiency of a single scale for accurate analysis of the features of a psychotic disorder. At onset, a comparison using the simple presence/absence of symptoms showed scant differences among groups, while differences emerged if symptom severity was included in the comparison. Functioning at 3- and 5-year follow-ups showed a significantly better outcome in the BPP group and more substantial deterioration, with similar evolution, in the SPh and SA groups. The integration of several rating scales differentiated between diagnostic groups more effectively. The similar adult functioning outcome in the SPh and SA groups showed how difficult it is to clearly separate these two disorders.

  12. Increased Insomnia Symptoms Predict the Onset of Back Pain among Employed Adults

    PubMed Central

    2014-01-01

    Background Back pain is among the most prevalent pain disorders causing chronic disability among adults, and insomnia is a common co-morbidity. However, whether insomnia precedes back pain or vice versa remains unclear. The current study tested the temporal association between insomnia and back pain. Methods A longitudinal design was used to investigate whether changes in insomnia over time predict the onset of back pain and vice versa. The study was conducted on a cohort of active healthy working adults (N = 2,131, 34% women) at three time points (T1, T2, and T3) over a period of 3.7 years (range = 2.2–5.12) years. Logistic regression analysis was used to test whether increased insomnia symptoms from T1 to T2 predicted the onset of new back pain. Ordinary least squares regression was used to test whether the existence of back pain at T2 predicted an increase in insomnia from T2 to T3. Results The results indicated that after controlling for socioeconomic variables, self-reported health, lifestyle behaviors, and anthropometrics, a T1–T2 increase in insomnia symptoms was associated with a 1.40-fold increased risk of back pain at T3 (OR = 1.40; 95% CI = 1.10–1.71). No support was found for reverse causation; i.e., that back pain predicts subsequent increase in insomnia. Conclusions Insomnia appears to be a risk factor in the development of back pain in healthy individuals. However, no evidence of reverse causation was found. PMID:25084165

  13. Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium

    PubMed Central

    Postma, D. S.; Moffatt, M. F.; Jarvis, D.; Ramasamy, A.; Wjst, M.; Omenaas, E. R.; Bouzigon, E.; Demenais, F.; Nadif, R.; Siroux, V.; Polonikov, A. V.; Solodilova, M.; Ivanov, V. P.; Curjuric, I.; Imboden, M.; Kumar, A.; Probst-Hensch, N.; Ogorodova, L. M.; Puzyrev, V. P.; Bragina, E. Yu; Freidin, M. B.; Nolte, I. M.; Farrall, A. M.; Cookson, W. O. C. M.; Strachan, D. P.; Koppelman, G. H.; Boezen, H. M.

    2017-01-01

    Background Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. Methods We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. Results First approach: 50 SNPs were selected based on an overall interaction effect at p<10−4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10−5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10−4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10−4; replication: ORint = 1.40, p = 0.03). Conclusions Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma. PMID:28253294

  14. The effect of tremor onset on middle cerebellar peduncle of Parkinson's disease.

    PubMed

    Sako, Wataru; Murakami, Nagahisa; Miyazaki, Yoshimichi; Abe, Takashi; Harada, Masafumi; Izumi, Yuishin; Kaji, Ryuji

    2015-11-15

    The majority of studies of Parkinson's disease (PD) focused on basal ganglia initially; however, accumulating evidence suggests cerebellar involvement in pathophysiology. We aimed to investigate the effects of tremor onset on middle cerebellar peduncle (MCP) width of PD patients and of disease duration on differential diagnosis. We measured MCP width of 81 PD, 34 multiple system atrophy (MSA) and 16 normal controls, using MRI. A meta-analysis was performed including two previous and the present studies. We carried out correlation analysis between disease duration and MCP width separately in subgroup of PD with or without tremor onset. Receiver operating characteristic curves were analyzed. Our meta-analysis indicated that MCP width was significantly smaller in MSA relative to PD with homogeneous studies. There was significant correlation between disease duration and MCP width in PD without tremor onset. In contrast, there was no correlation observed in PD with tremor onset. Subclassification according to disease duration showed improved area under curve of PD vs. MSA with predominant parkinsonian features. MCP width could be a valuable tool for differential diagnosis. Our finding suggested that MCP was impaired in advanced stage of PD without tremor onset as part of the abnormality of the cerebellar system.

  15. Could clinical profile influence CSF biomarkers in early-onset Alzheimer disease?

    PubMed

    Koric, Lejla; Felician, Olivier; Guedj, Eric; Hubert, Anne Michele; Mancini, Julien; Boucraut, Jose; Ceccaldi, Mathieu

    2010-01-01

    In common forms of Alzheimer disease (AD), anterograde memory impairment is the first deficit to occur. However, the disease, especially in its presenile forms, may also manifest itself through initial deficits that are predominantly of a nonmemory type. These distinct clinical profiles, which reflect the distinct topography of the underlying pathologic processes, may also differ in terms of their cerebrospinal fluid (CSF) markers. The aim of this study was to assess the levels of total tau, phosphorylated tau, and amyloid-beta 42 peptide in the CSF of "atypical" (nonmemory) early-onset AD patients. CSF biomarkers were evaluated in 22 atypical patients, and compared with those from a group of 13 "typical" patients, with a memory onset form of the disease. Our results show that independently of age, disease duration, education level, and clinical severity indices, patients with an atypical onset have significantly higher levels of total tau in the CSF (P=0.023). These findings indicate that an assessment of CSF biomarkers may be of particular use in the clinical diagnosis of "atypical-onset" forms of early-onset AD in which the initial symptoms involve language and visuospatial abilities rather than memory. In addition, they highlight the heterogeneity of pathologic processes in AD, suggesting more intense degeneration in the forms of the disease that primarily involve neocortical structures.

  16. Is adult ADHD a childhood-onset neurodevelopmental disorder? Evidence from a 4-decade longitudinal cohort study

    PubMed Central

    Moffitt, Terrie E.; Houts, Renate; Asherson, Philip; Belsky, Daniel W; Corcoran, David L; Hammerle, Maggie; Harrington, Honalee; Hogan, Sean; Meier, Madeline; Polanczyk, Guilherme V.; Poulton, Richie; Ramrakha, Sandhya; Sugden, Karen; Williams, Benjamin; Rohde, Luis Augusto; Caspi, Avshalom

    2015-01-01

    Objective Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective-longitudinal study has described the childhoods of the adult-ADHD population. We report follow-back analyses of ADHD cases diagnosed in adulthood, alongside follow-forward analyses of ADHD cases diagnosed in childhood, in one cohort. Method Participants belonged to a representative birth cohort of 1,037 individuals born in Dunedin, New Zealand in 1972-73 and followed to age 38, with 95% retention. Symptoms of ADHD, associated clinical features, comorbid disorders, neuropsychological deficits, GWAS-derived polygenic risk, and life impairment indicators were assessed. Data sources were participants, parents, teachers, informants, neuropsychological testing, and administrative records. Adult ADHD diagnoses used DSM5 criteria, apart from onset-age and cross-setting corroboration, which were study outcomes. Results As expected, the childhood-ADHD group showed 6% prevalence, male excess, childhood comorbid disorders, neurocognitive deficits, polygenic risk, and, despite having outgrown their ADHD diagnosis, residual adult life impairment. As expected, the adult-ADHD group showed 3% prevalence, gender balance, adult substance dependence, adult life impairment, and treatment contact. Unexpectedly, the childhood-ADHD and adult-ADHD groups comprised virtually non-overlapping sets; 90% of adult-ADHD cases lacked a history of childhood ADHD. Also unexpectedly, the adult-ADHD group did not show tested neuropsychological deficits in childhood or adulthood, nor did they show polygenic risk for childhood ADHD. Conclusion Findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder. If this finding is replicated, then the disorder's place in the classification system must be reconsidered, and research must investigate the etiology of adult ADHD. PMID:25998281

  17. ApoE Genotype and Alzheimer's Disease in Adults with Down Syndrome: Meta-Analysis.

    ERIC Educational Resources Information Center

    Prashner, V. P.; Chowdhury, T. A.; Rowe, B. R.; Bain, S. C.

    1997-01-01

    ApoE gene polymorphism was examined in 100 adults with Down syndrome with and without dementia (Alzheimer's disease) and 346 control subjects. Additionally, a meta analysis of studies (total N=480 subjects) was performed. Results indicated a similar incidence of the gene across groups but subjects with the allele tended to an earlier onset of…

  18. Nanoscale studies link amyloid maturity with polyglutamine diseases onset

    NASA Astrophysics Data System (ADS)

    Ruggeri, F. S.; Vieweg, S.; Cendrowska, U.; Longo, G.; Chiki, A.; Lashuel, H. A.; Dietler, G.

    2016-08-01

    The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington’s disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.

  19. Nanoscale studies link amyloid maturity with polyglutamine diseases onset

    PubMed Central

    Ruggeri, F. S.; Vieweg, S.; Cendrowska, U.; Longo, G.; Chiki, A.; Lashuel, H. A.; Dietler, G.

    2016-01-01

    The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington’s disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity. PMID:27499269

  20. Sex-specific associations of low birth weight with adult-onset diabetes and measures of glucose homeostasis: Brazilian Longitudinal Study of Adult Health

    PubMed Central

    Yarmolinsky, James; Mueller, Noel T; Duncan, Bruce B; Chor, Dóra; Bensenor, Isabela M; Griep, Rosane H; Appel, Lawrence J; Barreto, Sandhi M; Schmidt, Maria Inês

    2016-01-01

    Emerging evidence suggests sex differences in the early origins of adult metabolic disease, but this has been little investigated in developing countries. We investigated sex-specific associations between low birth weight (LBW; <2.5 kg) and adult-onset diabetes in 12,525 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Diabetes was defined by self-reported information and laboratory measurements. In confounder-adjusted analyses, LBW (vs. 2.5–4 kg) was associated with higher prevalence of diabetes in women (Prevalence Ratio (PR) 1.54, 95% CI: 1.32–1.79), not in men (PR 1.06, 95% CI: 0.91–1.25; Pheterogeneity = 0.003). The association was stronger among participants with maternal diabetes (PR 1.60, 95% CI: 1.35–1.91), than those without (PR 1.15, 95% CI: 0.99–1.32; Pheterogeneity = 0.03). When jointly stratified by sex and maternal diabetes, the association was observed for women with (PR 1.77, 95% CI: 1.37–2.29) and without (PR 1.45, 95% CI: 1.20–1.75) maternal diabetes. In contrast, in men, LBW was associated with diabetes in participants with maternal diabetes (PR 1.45, 95% CI: 1.15–1.83), but not in those without (PR 0.92, 95% CI: 0.74–1.14). These sex-specific findings extended to continuous measures of glucose homeostasis. LBW was associated with higher diabetes prevalence in Brazilian women, and in men with maternal diabetes, suggesting sex-specific intrauterine effects on adult metabolic health. PMID:27845438

  1. Understanding the Delay in Onset of Pagets Disease of Bone

    DTIC Science & Technology

    2015-09-01

    has passed, is unclear. Understanding the genetics underlying this disease process and how the predisposing mutation interacts with the measles virus...suppressing gene expression in the cell. Then, over the years, a chance genetic event in a single bone cell containing the measles virus results in the...we were able to generate a genetic signature from this comparison of genes that were turned on or turned off in the presence of the measles’ genome

  2. Borderlines between Sarcopenia and Mild Late-Onset Muscle Disease

    PubMed Central

    Palmio, Johanna; Udd, Bjarne

    2014-01-01

    Numerous natural or disease-related alterations occur in different tissues of the body with advancing age. Sarcopenia is defined as age-related decrease of muscle mass and strength beginning in mid-adulthood and accelerating in people older than 60 years. Pathophysiology of sarcopenia involves both neural and muscle dependent mechanisms and is enhanced by multiple factors. Aged muscles show loss in fiber number, fiber atrophy, and gradual increase in the number of ragged red fibers and cytochrome c oxidase-negative fibers. Generalized loss of muscle tissue and increased amount of intramuscular fat are seen on muscle imaging. However, the degree of these changes varies greatly between individuals, and the distinction between normal age-related weakening of muscle strength and clinically significant muscle disease is not always obvious. Because some of the genetic myopathies can present at a very old age and be mild in severity, the correct diagnosis is easily missed. We highlight this difficult borderline zone between sarcopenia and muscle disease by two examples: LGMD1D and myotonic dystrophy type 2. Muscle magnetic resonance imaging (MRI) is a useful tool to help differentiate myopathies from sarcopenia and to reach the correct diagnosis also in the elderly. PMID:25324776

  3. Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Caused by a Novel R782G Mutation in CSF1R

    PubMed Central

    Foulds, Nicola; Pengelly, Reuben J.; Hammans, Simon R.; Nicoll, James A. R.; Ellison, David W.; Ditchfield, Adam; Beck, Sarah; Ennis, Sarah

    2015-01-01

    We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration with axonal swellings and pigmented macrophages. The few recently reported families with CSF1R mutations had been previously labelled “hereditary diffuse leukencephalopathy with axonal spheroids” (HDLS) and “pigmentary orthochromatic leukodystrophy” (POLD), disorders which now appear to form a disease continuum. The term “adult-onset leukoencephalopathy with axonal spheroids and pigmented glia” (ALSP) has been proposed to encompass this spectrum. As CSF1R regulates microglia this mutation implies that dysregulation of microglia is the primary cause of the disease. PMID:25975230

  4. Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Caused by a Novel R782G Mutation in CSF1R.

    PubMed

    Foulds, Nicola; Pengelly, Reuben J; Hammans, Simon R; Nicoll, James A R; Ellison, David W; Ditchfield, Adam; Beck, Sarah; Ennis, Sarah

    2015-05-15

    We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration with axonal swellings and pigmented macrophages. The few recently reported families with CSF1R mutations had been previously labelled "hereditary diffuse leukencephalopathy with axonal spheroids" (HDLS) and "pigmentary orthochromatic leukodystrophy" (POLD), disorders which now appear to form a disease continuum. The term "adult-onset leukoencephalopathy with axonal spheroids and pigmented glia" (ALSP) has been proposed to encompass this spectrum. As CSF1R regulates microglia this mutation implies that dysregulation of microglia is the primary cause of the disease.

  5. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  6. Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

    PubMed

    das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes

    2016-04-01

    The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality.

  7. Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease

    PubMed Central

    Caso, Francesco; Galozzi, Paola; Costa, Luisa; Sfriso, Paolo; Cantarini, Luca; Punzi, Leonardo

    2015-01-01

    The recent identification of genetic mutations leading to dysfunction of inflammatory and apoptotic pathways, has allowed to characterise a group of diseases, recognised as monogenic autoinflammatory syndromes. Among those, Blau syndrome (BS) and early-onset sarcoidosis (EOS) have been identified as familial and sporadic phenotypes of the same non-caseating granulomatous form. Both the diseases are caused by mutations in the CARD15/NOD2 gene, encoding the cytosolic NOD2 protein, one of the key molecules in the regulation of innate immunity. Clinical onset is typically located in the first years of life and phenotype is characterised by simultaneous or less articular, cutaneous and ocular non-caseating granulomatous inflammation, which can be variably associated with a heterogeneous systemic spectrum. The CARD15/NOD2 gene has also been identified as one of the genes linked to susceptibility to Crohn's disease (CD), a common polygenic inflammatory granulomatous bowel disease. The heightened nuclear factor-κB activity, found in the intestinal tissue of patients affected by CD, has probably a genetic cause related to several CARD15/NOD2 polymorphisms. Other substitutions in the CARD15/NOD2 gene have also been found in a recently described disorder, called NOD2-associated autoinflammatory disease, which shares several clinical characteristics with BS and EOS. This review attempts to describe these diseases on the basis of the most recent evidences. We described genetic and clinical aspects, mainly focusing on BS and EOS, the most representative diseases of autoinflammatory granulomatous diseases, with the ultimate purpose to expand their knowledge. PMID:26509073

  8. How Does Age at Onset Influence the Outcome of Autoimmune Diseases?

    PubMed Central

    Amador-Patarroyo, Manuel J.; Rodriguez-Rodriguez, Alberto; Montoya-Ortiz, Gladis

    2012-01-01

    The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs), these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1D), Sjögren's syndrome, and autoimmune thyroiditis (AITD). Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D), while for others it does not have a significant influence on the course of disease (i.e., SS) or no unanimous consensus exists (i.e., RA and MS). PMID:22195277

  9. Younger age at onset of sporadic Parkinson's disease among subjects occupationally exposed to metals and pesticides

    PubMed Central

    Farb, David H.; Ozer, Josef; Feldman, Robert G.; Durso, Raymon

    2014-01-01

    An earlier age at onset of Parkinson's disease (PD) has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was minimized by including only sporadic cases of PD with no family history of the disease (n=58). Independent samples Student t-test revealed that subjects with occupational exposure to metals and/or pesticides (n=36) were significantly (p=0.013) younger than unexposed controls (n=22). These subjects were then divided into three groups [high (n=18), low (n=18), and unexposed (n=22)] to ascertain if duration of exposure further influenced age at onset of PD. One-way ANOVA revealed that subjects in the high exposure group were significantly (p=0.0121) younger (mean age: 50.33 years) than unexposed subjects (mean age: 60.45 years). Subjects were also stratified by exposure type (metals vs. pesticides). These results suggest that chronic exposure to metals and pesticides is associated with a younger age at onset of PD among patients with no family history of the disease and that duration of exposure is a factor in the magnitude of this effect. PMID:26109889

  10. Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

    PubMed Central

    Cardin, Velia

    2016-01-01

    Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

  11. Disease onset and aging in the world of circular RNAs.

    PubMed

    Maiese, Kenneth

    Circular ribonucleic acids (circRNAs) are non-coding RNAs of approximately 100 nucleotides in length with thousands of members in mammalian cells. The presence of circRNAs is believed to be even greater than that of messenger RNAs. Identification of circRNAs occurred approximately 37 years ago with the subsequent demonstration that covalent bonds are necessary for the unique circular structure of these ribonucleic acids. However, present understanding of the complex biological role of circRNAs remains limited and requires further elucidation. CircRNAs may impact aging, multiple disorders, function as biomarkers, and are able to regulate gene expression by acting as effective microRNA (miRNA) sponges. New work suggests that circRNAs are vital for the modulation of cellular senescence and programmed cell death pathways such as apoptosis. These non-coding RNAs can control cell cycle progression, cellular proliferation, and cellular survival impacting disorders linked to aging, cardiovascular disease, and atherosclerosis through pathways that involve cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase inhibitor 1 (p21), and mammalian forkhead transcription factors. In addition, circRNAs can oversee cellular metabolism and disorders such as diabetes mellitus through the regulation of insulin signaling as well as limit tumor progression through Wnt signaling and β-catenin pathways. Further understanding of the biology of circRNAs offers great promise for the targeting of novel strategies against a wide spectrum of disease entities.

  12. Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

    PubMed

    Case, Laura E; Koeberl, Dwight D; Young, Sarah P; Bali, Deeksha; DeArmey, Stephanie M; Mackey, Joanne; Kishnani, Priya S

    2008-12-01

    Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment.

  13. [A female patient with late-onset schizophrenia and fear of Katwijk disease].

    PubMed

    Veerman, S R T; Sno, H N; Ravelli, D P; Roos, R A C

    2009-01-01

    A 66-year-old patient had suffered from late-onset schizophrenia from the age of 44. Her family history included reports of brain haemorrhages, possibly resulting from hereditary amyloidal angiopathy of the Dutch type (Katwijk disease). She was very afraid for having this disease. The progression of the psychiatric symptoms and the age at which they began, led us to suspect an organic process. Differential diagnoses that were discussed included cerebral amyloidal angiopathy, frontal lobe dementia and Huntington's disease.

  14. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset.

    PubMed Central

    Brookmeyer, R; Gray, S; Kawas, C

    1998-01-01

    OBJECTIVES: The goal of this study was to project the future prevalence and incidence of Alzheimer's disease in the United States and the potential impact of interventions to delay disease onset. METHODS: The numbers of individuals in the United States with Alzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections. RESULTS: in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: 1.09 to 4.58 million); of these individuals, 68% were female. It is projected that the prevalence will nearly quadruple in the next 50 years, by which time approximately 1 in 45 Americans will be afflicted with the disease. Currently, the annual number of new incident cases in 360,000. If interventions could delay onset of the disease by 2 years, after 50 years there would be nearly 2 million fewer cases than projected; if onset could be delayed by 1 year, there would be nearly 800,000 fewer prevalent cases. CONCLUSIONS: As the US population ages, Alzheimer's disease will become an enormous public health problem. interventions that could delay disease onset even modestly would have a major public health impact. PMID:9736873

  15. Developmental programming: variations in early growth and adult disease.

    PubMed

    Gallo, Linda A; Tran, Melanie; Moritz, Karen M; Wlodek, Mary E

    2013-11-01

    Suboptimal conditions in utero are associated with the development of adult-onset diseases in offspring. Uteroplacental insufficiency in rats is a well-established animal model used to mimic and study the effects of developmental insults relevant to countries of abundant nutrient supply. However, wide-ranging outcomes for the offspring are apparent between the different investigators that use this model and also between cohorts generated in our laboratory. We aimed to explore the reasons for variability in rat models of uteroplacental insufficiency between different investigators and also between our own animal cohorts. We suggest differences in growth and disease development reflect uniqueness in susceptibility and highlight the complexity of interactions between genetic potential and environmental exposures. The impact of adverse exposures in utero has been described as having far-reaching effects that extend well beyond the first, directly exposed generation. However, the resulting phenotypes are not consistent between generations. This suggests that programmed effects are established de novo in each generation and challenges the prediction of disease. Characterization of growth and disease in the numerous rat models has led to our understanding of the impact of early life experiences on adult health. In order to drive the development of preventative and/or treatment strategies, future studies should focus on identifying the initial cause(s) of uteroplacental insufficiency, including genetic origins and the influence of poor diets.

  16. Association of hypertension with coronary artery disease onset in the Lebanese population.

    PubMed

    Milane, Aline; Abdallah, Jad; Kanbar, Roy; Khazen, Georges; Ghassibe-Sabbagh, Michella; Salloum, Angelique K; Youhanna, Sonia; Saad, Aline; El Bayeh, Hamid; Chammas, Elie; Platt, Daniel E; Hager, Jörg; Gauguier, Dominique; Zalloua, Pierre; Abchee, Antoine

    2014-01-01

    The onset of coronary artery disease (CAD) is influenced by cardiovascular risk factors that often occur in clusters and may build on one another. The objective of this study is to examine the relationship between hypertension and CAD age of onset in the Lebanese population. This retrospective analysis was performed on data extracted from Lebanese patients (n = 3,753). Logistic regression examined the association of hypertension with the age at CAD diagnosis after controlling for other traditional risk factors. The effect of antihypertensive drugs and lifestyle changes on the onset of CAD was also investigated. Results showed that hypertension is associated with late onset CAD (OR=0.656, 95% CI=0.504-0.853, p=0.001). Use of antihypertensive drugs showed a similar association with delayed CAD onset. When comparing age of onset in CAD patients with traditional risk factors such as hypertension, diabetes, hyperlipidemia, obesity, smoking and family history of CAD, the age of onset was significantly higher for patients with hypertension compared to those with any of the other risk factors studied (p < 0.001). In conclusion, hypertension and its treatment are associated with late coronary atherosclerotic manifestations in Lebanese population. This observation is currently under investigation to clarify its genetic and/or environmental mechanisms.

  17. Characteristics of familial aggregation in early-onset Alzheimer`s disease: Evidence of subgroups

    SciTech Connect

    Campion, D.; Martinez, M.; Babron, M.C.

    1995-06-19

    Characteristics of familial aggregation of Alzheimer`s Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early-onset Alzheimer`s disease. 58 refs., 5 figs., 2 tabs.

  18. No Association Between Time of Onset of Hearing Loss (Childhood Versus Adulthood) and Self-Reported Hearing Handicap in Adults

    PubMed Central

    Tambs, Kristian; Engdahl, Bo

    2015-01-01

    Purpose This study examined the association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap in adults. Methods This is a population-based cohort study of 2,024 adults (mean = 48 years) with hearing loss (binaural pure-tone average 0.5–4 kHz ≥ 20 dB HL) who completed a hearing handicap questionnaire. In childhood, the same persons (N = 2,024) underwent audiometry in a school investigation (at ages 7, 10, and 13 years), in which 129 were diagnosed with sensorineural hearing loss (binaural pure-tone average 0.5–4 kHz ≥ 20 dB HL), whereas 1,895 had normal hearing thresholds. Results Hearing handicap was measured in adulthood as the sum-score of various speech perception and social impairment items (15 items). The sum-score increased with adult hearing threshold level (p < .001). After adjustment for adult hearing threshold level, hearing aid use, adult age, sex, and socioeconomic status, there was no significant difference in hearing handicap sum-score between the group with childhood-onset hearing loss (n = 129) and the group with adult-onset hearing loss (n = 1,895; p = .882). Conclusion Self-reported hearing handicap in adults increased with hearing threshold level. After adjustment for adult hearing threshold level, this cohort study revealed no significant association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap. PMID:26649831

  19. Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies

    PubMed Central

    Rava, Marta; Ahmed, Ismail; Kogevinas, Manolis; Le Moual, Nicole; Bouzigon, Emmanuelle; Curjuric, Ivan; Dizier, Marie-Hélène; Dumas, Orianne; Gonzalez, Juan R.; Imboden, Medea; Mehta, Amar J.; Tubert-Bitter, Pascale; Zock, Jan-Paul; Jarvis, Deborah; Probst-Hensch, Nicole M.; Demenais, Florence; Nadif, Rachel

    2016-01-01

    Background: The biological mechanisms by which cleaning products and disinfectants—an emerging risk factor—affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (G × E) may help identify new genes related to adult-onset asthma. Objectives: We identified interactions between genetic polymorphisms of a large set of genes involved in the response to oxidative stress and occupational exposures to low molecular weight (LMW) agents or irritants on adult-onset asthma. Methods: Our data came from three large European cohorts: Epidemiological Family-based Study of the Genetics and Environment of Asthma (EGEA), Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), and European Community Respiratory Health Survey in Adults (ECRHS). A candidate pathway–based strategy identified 163 genes involved in the response to oxidative stress and potentially related to exposures to LMW agents/irritants. Occupational exposures were evaluated using an asthma job-exposure matrix and job-specific questionnaires for cleaners and healthcare workers. Logistic regression models were used to detect G × E interactions, adjusted for age, sex, and population ancestry, in 2,599 adults (mean age, 47 years; 60% women, 36% exposed, 18% asthmatics). p-Values were corrected for multiple comparisons. Results: Ever exposure to LMW agents/irritants was associated with current adult-onset asthma [OR = 1.28 (95% CI: 1.04, 1.58)]. Eight single nucleotide polymorphism (SNP) by exposure interactions at five loci were found at p < 0.005: PLA2G4A (rs932476, chromosome 1), near PLA2R1 (rs2667026, chromosome 2), near RELA (rs931127, rs7949980, chromosome 11), PRKD1 (rs1958980, rs11847351, rs1958987, chromosome 14), and PRKCA (rs6504453, chromosome 17). Results were consistent across the three studies and after accounting for smoking. Conclusions: Using a pathway-based selection process, we identified novel genes potentially involved

  20. Cerebral Cell Renewal in Adult Mice Controls the Onset of Obesity

    PubMed Central

    Gouazé, Alexandra; Brenachot, Xavier; Rigault, Caroline; Krezymon, Alice; Rauch, Camille; Nédélec, Emmanuelle; Lemoine, Aleth; Gascuel, Jean; Bauer, Sylvian; Pénicaud, Luc; Benani, Alexandre

    2013-01-01

    The hypothalamus plays a crucial role in the control of the energy balance and also retains neurogenic potential into adulthood. Recent studies have reported the severe alteration of the cell turn-over in the hypothalamus of obese animals and it has been proposed that a neurogenic deficiency in the hypothalamus could be involved in the development of obesity. To explore this possibility, we examined hypothalamic cell renewal during the homeostatic response to dietary fat in mice, i.e., at the onset of diet-induced obesity. We found that switching to high-fat diet (HFD) accelerated cell renewal in the hypothalamus through a local, rapid and transient increase in cell proliferation, peaking three days after introducing the HFD. Blocking HFD-induced cell proliferation by central delivery of an antimitotic drug prevented the food intake normalization observed after HFD introduction and accelerated the onset of obesity. This result showed that HFD-induced dividing brain cells supported an adaptive anorectic function. In addition, we found that the percentage of newly generated neurons adopting a POMC-phenotype in the arcuate nucleus was increased by HFD. This observation suggested that the maturation of neurons in feeding circuits was nutritionally regulated to adjust future energy intake. Taken together, these results showed that adult cerebral cell renewal was remarkably responsive to nutritional conditions. This constituted a physiological trait required to prevent severe weight gain under HFD. Hence this report highlighted the amazing plasticity of feeding circuits and brought new insights into our understanding of the nutritional regulation of the energy balance. PMID:23967273

  1. A course on the transition to adult care of patients with childhood-onset chronic illnesses.

    PubMed

    Hagood, James S; Lenker, Claire V; Thrasher, Staci

    2005-04-01

    Children with special health care needs born today have a 90% chance of surviving into adulthood, making their transition to adult systems of care an issue that will affect almost all physicians. However, many adult generalists and specialists are not familiar with the management of chronic diseases that begin in childhood. While the public health system has made transition to appropriate adult care a priority, and many specialty organizations have endorsed this concept, there are no published studies addressing how the concept of transition can be taught to medical students or residents. The authors describe a one-week course for medical students, begun in 2001 at their institution, that addresses the transition for youth with special health care needs, emphasizing patient and family-centered care, cultural competence, and decision making in end-of-life issues. Cystic fibrosis, a common genetic disease with increasing life expectancy, is used as the model for the course. Involvement of interdisciplinary faculty, interviews with youth with special health care needs and family caregivers, readings from academic and nonacademic literature, and group discussions are presented as teaching methods. Key insights based on experience with the course are the need to include the voices of patients and families, the use of faculty from various professions and specialties to model interdisciplinary care, and the insight that problems specific to transition offer into contemporary health care financing. Future studies should measure the impact of such courses on students' knowledge of transition issues, and determine essential information required for physicians in practice.

  2. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    SciTech Connect

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  3. ATP1A3 Mutation in Adult Rapid-Onset Ataxia

    PubMed Central

    Sweadner, Kathleen J.; Toro, Camilo; Whitlow, Christopher T.; Snively, Beverly M.; Cook, Jared F.; Ozelius, Laurie J.; Markello, Thomas C.; Brashear, Allison

    2016-01-01

    A 21-year old male presented with ataxia and dysarthria that had appeared over a period of months. Exome sequencing identified a de novo missense variant in ATP1A3, the gene encoding the α3 subunit of Na,K-ATPase. Several lines of evidence suggest that the variant is causative. ATP1A3 mutations can cause rapid-onset dystonia-parkinsonism (RDP) with a similar age and speed of onset, as well as severe diseases of infancy. The patient’s ATP1A3 p.Gly316Ser mutation was validated in the laboratory by the impaired ability of the expressed protein to support the growth of cultured cells. In a crystal structure of Na,K-ATPase, the mutated amino acid was directly apposed to a different amino acid mutated in RDP. Clinical evaluation showed that the patient had many characteristics of RDP, however he had minimal fixed dystonia, a defining symptom of RDP. Successive magnetic resonance imaging (MRI) revealed progressive cerebellar atrophy, explaining the ataxia. The absence of dystonia in the presence of other RDP symptoms corroborates other evidence that the cerebellum contributes importantly to dystonia pathophysiology. We discuss the possibility that a second de novo variant, in ubiquilin 4 (UBQLN4), a ubiquitin pathway component, contributed to the cerebellar neurodegenerative phenotype and differentiated the disease from other manifestations of ATP1A3 mutations. We also show that a homozygous variant in GPRIN1 (G protein-regulated inducer of neurite outgrowth 1) deletes a motif with multiple copies and is unlikely to be causative. PMID:26990090

  4. ATP1A3 Mutation in Adult Rapid-Onset Ataxia.

    PubMed

    Sweadner, Kathleen J; Toro, Camilo; Whitlow, Christopher T; Snively, Beverly M; Cook, Jared F; Ozelius, Laurie J; Markello, Thomas C; Brashear, Allison

    2016-01-01

    A 21-year old male presented with ataxia and dysarthria that had appeared over a period of months. Exome sequencing identified a de novo missense variant in ATP1A3, the gene encoding the α3 subunit of Na,K-ATPase. Several lines of evidence suggest that the variant is causative. ATP1A3 mutations can cause rapid-onset dystonia-parkinsonism (RDP) with a similar age and speed of onset, as well as severe diseases of infancy. The patient's ATP1A3 p.Gly316Ser mutation was validated in the laboratory by the impaired ability of the expressed protein to support the growth of cultured cells. In a crystal structure of Na,K-ATPase, the mutated amino acid was directly apposed to a different amino acid mutated in RDP. Clinical evaluation showed that the patient had many characteristics of RDP, however he had minimal fixed dystonia, a defining symptom of RDP. Successive magnetic resonance imaging (MRI) revealed progressive cerebellar atrophy, explaining the ataxia. The absence of dystonia in the presence of other RDP symptoms corroborates other evidence that the cerebellum contributes importantly to dystonia pathophysiology. We discuss the possibility that a second de novo variant, in ubiquilin 4 (UBQLN4), a ubiquitin pathway component, contributed to the cerebellar neurodegenerative phenotype and differentiated the disease from other manifestations of ATP1A3 mutations. We also show that a homozygous variant in GPRIN1 (G protein-regulated inducer of neurite outgrowth 1) deletes a motif with multiple copies and is unlikely to be causative.

  5. Intact sensory-motor network structure and function in far from onset premanifest Huntington's disease.

    PubMed

    Gorges, Martin; Müller, Hans-Peter; Mayer, Isabella Maria Sophie; Grupe, Gesa Sophie; Kammer, Thomas; Grön, Georg; Kassubek, Jan; Landwehrmeyer, G Bernhard; Wolf, Robert Christian; Orth, Michael

    2017-03-07

    Structural and functional changes attributable to the neurodegenerative process in Huntington's disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (11 preHD, 22 controls) as well as electrophysiological measurements (12 preHD, 13 controls). There were no significant differences in white matter macro- and microstructure between far from onset preHD participants and controls. Functional connectivity in a basal ganglia-thalamic and motor networks, all measures of the motor efferent and sensory afferent pathways as well as sensory-motor integration were also similar in far from onset preHD and controls. With the methods used in far from onset preHD sensory-motor neural macro- or micro-structure and brain function were similar to healthy controls. This suggests that any observable structural and functional change in preHD nearer to onset, or in manifest HD, at least using comparable techniques such as in this study, most likely reflects an ongoing neurodegenerative process.

  6. Late onset fulminant Wilson's disease: a case report and review of the literature.

    PubMed

    Weitzman, Ella; Pappo, Orit; Weiss, Peretz; Frydman, Moshe; Haviv-Yadid, Yael; Ben Ari, Ziv

    2014-12-14

    Wilson's disease (WD) is an autosomal recessive inherited disorder of hepatic copper metabolism. WD can be present in different clinical conditions, with the most common ones being liver disease and neuropsychiatric disturbances. Most cases present symptoms at < 40 years of age. However, few reports exist in the literature on patients in whom the disease presented beyond this age. In this report, we present a case of late onset fulminant WD in a 58-year-old patient in whom the diagnosis was established clinically, by genetic analysis of the ATP7B gene disclosing rare mutations (G1099S and c.1707+3insT) as well as by high hepatic copper content. We also reviewed the relevant literature. The diagnosis of WD with late onset presentation is easily overlooked. The diagnostic features and the genetic background in patients with late onset WD are not different from those in patients with early onset WD, except for the age. Effective treatments for this disorder that can be fatal are available and will prevent or reverse many manifestations if the disease is discovered early.

  7. Late onset fulminant Wilson’s disease: A case report and review of the literature

    PubMed Central

    Weitzman, Ella; Pappo, Orit; Weiss, Peretz; Frydman, Moshe; Haviv-Yadid, Yael; Ben Ari, Ziv

    2014-01-01

    Wilson’s disease (WD) is an autosomal recessive inherited disorder of hepatic copper metabolism. WD can be present in different clinical conditions, with the most common ones being liver disease and neuropsychiatric disturbances. Most cases present symptoms at < 40 years of age. However, few reports exist in the literature on patients in whom the disease presented beyond this age. In this report, we present a case of late onset fulminant WD in a 58-year-old patient in whom the diagnosis was established clinically, by genetic analysis of the ATP7B gene disclosing rare mutations (G1099S and c.1707+3insT) as well as by high hepatic copper content. We also reviewed the relevant literature. The diagnosis of WD with late onset presentation is easily overlooked. The diagnostic features and the genetic background in patients with late onset WD are not different from those in patients with early onset WD, except for the age. Effective treatments for this disorder that can be fatal are available and will prevent or reverse many manifestations if the disease is discovered early. PMID:25516681

  8. A Deeper Look into Type 1 Diabetes – Imaging Immune Responses during Onset of Disease

    PubMed Central

    Christoffersson, Gustaf; von Herrath, Matthias G.

    2016-01-01

    Cytotoxic T lymphocytes execute the killing of insulin-producing beta cells during onset of type 1 diabetes mellitus (T1D). The research community has come far in dissecting the major events in the development of this disease, but still the trigger and high-resolved information of the immunological events leading up to beta cell loss are missing. During the past decades, intravital imaging of immune responses has led to significant scientific breakthroughs in diverse models of disease, including T1D. Dynamic imaging of immune cells at the pancreatic islets during T1D onset has been made possible through the development of both advanced microscopes, and animal models that allow long-term immobilization of the pancreas. The use of these modalities has revealed a milling microenvironment at the pancreatic islets during disease onset with a plethora of active players. Clues to answering the remaining questions in this disease may lie in intravital imaging, including how key immune cells traffic to and from the pancreas, and how cells interact at this target tissue. This review highlights and discusses recent studies, models, and techniques focused to understand the immune responses during T1D onset through intravital imaging. PMID:27574523

  9. Age at onset of Alzheimer's disease: clue to the relative importance of etiologic factors

    SciTech Connect

    Horner, R.D.

    1987-09-01

    Clues to the relative importance of possible etiologic factors for dementia of the Alzheimer type may be gained by examining the fit of case series to Sartwell's model of the distribution of incubation periods. If age at disease onset is used as the incubation period of this disease, a genetic or environmental factor acting during the prenatal period is suggested if the distribution of these ages fits the lognormal curve; otherwise, environmental factors acting after birth are implicated. Case series were identified from the literature. Four case series were found which contained sufficiently detailed data to permit this secondary analysis; only one case series was population-based. The distribution of age at disease onset for each series was graphically and statistically assessed for fit to the logarithmic normal distribution. Each case series fit the lognormal curve well. This suggests that research into the etiology of dementia of the Alzheimer type should focus on the prenatal experiences of patients with this disease.

  10. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    PubMed Central

    Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga; Bohlen, Stefan; Bonelli, Raphael M.; Bos, Reineke; Bourne, Colin; Bradbury, Alyson; Brockie, Peter; Brown, Felicity; Bruno, Stefania; Bryl, Anna; Buck, Andrea; Burg, Sabrina; Burgunder, Jean-Marc; Burns, Peter; Burrows, Liz; Busquets, Nuria; Busse, Monica; Calopa, Matilde; Carruesco, Gemma T.; Casado, Ana Gonzalez; Catena, Judit López; Chu, Carol; Ciesielska, Anna; Clapton, Jackie; Clayton, Carole; Clenaghan, Catherine; Coelho, Miguel; Connemann, Julia; Craufurd, David; Crooks, Jenny; Cubillo, Patricia Trigo; Cubo, Esther; Curtis, Adrienne; De Michele, Giuseppe; De Nicola, A.; de Souza, Jenny; de Weert, A. Marit; de Yébenes, Justo Garcia; Dekker, M.; Descals, A. Martínez; Di Maio, Luigi; Di Pietro, Anna; Dipple, Heather; Dose, Matthias; Dumas, Eve M.; Dunnett, Stephen; Ecker, Daniel; Elifani, F.; Ellison-Rose, Lynda; Elorza, Marina D.; Eschenbach, Carolin; Evans, Carole; Fairtlough, Helen; Fannemel, Madelein; Fasano, Alfonso; Fenollar, Maria; Ferrandes, Giovanna; Ferreira, Jaoquim J.; Fillingham, Kay; Finisterra, Ana Maria; Fisher, K.; Fletcher, Amy; Foster, Jillian; Foustanos, Isabella; Frech, Fernando A.; Fullam, Robert; Fullham, Ruth; Gago, Miguel; García, RocioGarcía-Ramos; García, Socorro S.; Garrett, Carolina; Gellera, Cinzia; Gill, Paul; Ginestroni, Andrea; Golding, Charlotte; Goodman, Anna; Gørvell, Per; Grant, Janet; Griguoli, A.; Gross, Diana; Guedes, Leonor; BascuñanaGuerra, Monica; Guerra, Maria Rosalia; Guerrero, Rosa; Guia, Dolores B.; Guidubaldi, Arianna; Hallam, Caroline; Hamer, Stephanie; Hammer, Kathrin; Handley, Olivia J.; Harding, Alison; Hasholt, Lis; Hedge, Reikha; Heiberg, Arvid; Heinicke, Walburgis; Held, Christine; Hernanz, Laura Casas; Herranhof, Briggitte; Herrera, Carmen Durán; Hidding, Ute; Hiivola, Heli; Hill, Susan; Hjermind, Lena. E.; Hobson, Emma; Hoffmann, Rainer; Holl, Anna Hödl; Howard, Liz; Hunt, Sarah; Huson, Susan; Ialongo, Tamara; Idiago, Jesus Miguel R.; Illmann, Torsten; Jachinska, Katarzyna; Jacopini, Gioia; Jakobsen, Oda; Jamieson, Stuart; Jamrozik, Zygmunt; Janik, Piotr; Johns, Nicola; Jones, Lesley; Jones, Una; Jurgens, Caroline K.; Kaelin, Alain; Kalbarczyk, Anna; Kershaw, Ann; Khalil, Hanan; Kieni, Janina; Klimberg, Aneta; Koivisto, Susana P.; Koppers, Kerstin; Kosinski, Christoph Michael; Krawczyk, Malgorzata; Kremer, Berry; Krysa, Wioletta; Kwiecinski, Hubert; Lahiri, Nayana; Lambeck, Johann; Lange, Herwig; Laver, Fiona; Leenders, K.L.; Levey, Jamie; Leythaeuser, Gabriele; Lezius, Franziska; Llesoy, Joan Roig; Löhle, Matthias; López, Cristobal Diez-Aja; Lorenza, Fortuna; Loria, Giovanna; Magnet, Markus; Mandich, Paola; Marchese, Roberta; Marcinkowski, Jerzy; Mariotti, Caterina; Mariscal, Natividad; Markova, Ivana; Marquard, Ralf; Martikainen, Kirsti; Martínez, Isabel Haro; Martínez-Descals, Asuncion; Martino, T.; Mason, Sarah; McKenzie, Sue; Mechi, Claudia; Mendes, Tiago; Mestre, Tiago; Middleton, Julia; Milkereit, Eva; Miller, Joanne; Miller, Julie; Minster, Sara; Möller, Jens Carsten; Monza, Daniela; Morales, Blas; Moreau, Laura V.; Moreno, Jose L. López-Sendón; Münchau, Alexander; Murch, Ann; Nielsen, Jørgen E.; Niess, Anke; Nørremølle, Anne; Novak, Marianne; O'Donovan, Kristy; Orth, Michael; Otti, Daniela; Owen, Michael; Padieu, Helene; Paganini, Marco; Painold, Annamaria; Päivärinta, Markku; Partington-Jones, Lucy; Paterski, Laurent; Paterson, Nicole; Patino, Dawn; Patton, Michael; Peinemann, Alexander; Peppa, Nadia; Perea, Maria Fuensanta Noguera; Peterson, Maria; Piacentini, Silvia; Piano, Carla; Càrdenas, Regina Pons i; Prehn, Christian; Price, Kathleen; Probst, Daniela; Quarrell, Oliver; Quiroga, Purificacion Pin; Raab, Tina; Rakowicz, Maryla; Raman, Ashok; Raymond, Lucy; Reilmann, Ralf; Reinante, Gema; Reisinger, Karin; Retterstol, Lars; Ribaï, Pascale; Riballo, Antonio V.; Ribas, Guillermo G.; Richter, Sven; Rickards, Hugh; Rinaldi, Carlo; Rissling, Ida; Ritchie, Stuart; Rivera, Susana Vázquez; Robert, Misericordia Floriach; Roca, Elvira; Romano, Silvia; Romoli, Anna Maria; Roos, Raymond A.C.; Røren, Niini; Rose, Sarah; Rosser, Elisabeth; Rosser, Anne; Rossi, Fabiana; Rothery, Jean; Rudzinska, Monika; Ruíz, Pedro J. García; Ruíz, Belan Garzon; Russo, Cinzia Valeria; Ryglewicz, Danuta; Saft, Carston; Salvatore, Elena; Sánchez, Vicenta; Sando, Sigrid Botne; Šašinková, Pavla; Sass, Christian; Scheibl, Monika; Schiefer, Johannes; Schlangen, Christiane; Schmidt, Simone; Schöggl, Helmut; Schrenk, Caroline; Schüpbach, Michael; Schuierer, Michele; Sebastián, Ana Rojo; Selimbegovic-Turkovic, Amina; Sempolowicz, Justyna; Silva, Mark; Sitek, Emilia; Slawek, Jaroslaw; Snowden, Julie; Soleti, Francesco; Soliveri, Paola; Sollom, Andrea; Soltan, Witold; Sorbi, Sandro; Sorensen, Sven Asger; Spadaro, Maria; Städtler, Michael; Stamm, Christiane; Steiner, Tanja; Stokholm, Jette; Stokke, Bodil; Stopford, Cheryl; Storch, Alexander; Straßburger, Katrin; Stubbe, Lars; Sulek, Anna; Szczudlik, Andrzej; Tabrizi, Sarah; Taylor, Rachel; Terol, Santiago Duran-Sindreu; Thomas, Gareth; Thompson, Jennifer; Thomson, Aileen; Tidswell, Katherine; Torres, Maria M. Antequera; Toscano, Jean; Townhill, Jenny; Trautmann, Sonja; Tucci, Tecla; Tuuha, Katri; Uhrova, Tereza; Valadas, Anabela; van Hout, Monique S.E.; van Oostrom, J.C.H.; van Vugt, Jeroen P.P.; vanm, Walsem Marleen R.; Vandenberghe, Wim; Verellen-Dumoulin, Christine; Vergara, Mar Ruiz; Verstappen, C.C.P.; Verstraelen, Nichola; Viladrich, Celia Mareca; Villanueva, Clara; Wahlström, Jan; Warner, Thomas; Wehus, Raghild; Weindl, Adolf; Werner, Cornelius J.; Westmoreland, Leann; Weydt, Patrick; Wiedemann, Alexandra; Wild, Edward; Wild, Sue; Witjes-Ané, Marie-Noelle; Witkowski, Grzegorz; Wójcik, Magdalena; Wolz, Martin; Wolz, Annett; Wright, Jan; Yardumian, Pam; Yates, Shona; Yudina, Elizaveta; Zaremba, Jacek; Zaugg, Sabine W.; Zdzienicka, Elzbieta; Zielonka, Daniel; Zielonka, Euginiusz; Zinzi, Paola; Zittel, Simone; Zucker, Birgrit; Adams, John; Agarwal, Pinky; Antonijevic, Irina; Beck, Christopher; Chiu, Edmond; Churchyard, Andrew; Colcher, Amy; Corey-Bloom, Jody; Dorsey, Ray; Drazinic, Carolyn; Dubinsky, Richard; Duff, Kevin; Factor, Stewart; Foroud, Tatiana; Furtado, Sarah; Giuliano, Joe; Greenamyre, Timothy; Higgins, Don; Jankovic, Joseph; Jennings, Dana; Kang, Un Jung; Kostyk, Sandra; Kumar, Rajeev; Leavitt, Blair; LeDoux, Mark; Mallonee, William; Marshall, Frederick; Mohlo, Eric; Morgan, John; Oakes, David; Panegyres, Peter; Panisset, Michel; Perlman, Susan; Perlmutter, Joel; Quaid, Kimberly; Raymond, Lynn; Revilla, Fredy; Robertson, Suzanne; Robottom, Bradley; Sanchez-Ramos, Juan; Scott, Burton; Shannon, Kathleen; Shoulson, Ira; Singer, Carlos; Tabbal, Samer; Testa, Claudia; van, Kammen Dan; Vetter, Louise; Walker, Francis; Warner, John; Weiner, illiam; Wheelock, Vicki; Yastrubetskaya, Olga; Barton, Stacey; Broyles, Janice; Clouse, Ronda; Coleman, Allison; Davis, Robert; Decolongon, Joji; DeLaRosa, Jeanene; Deuel, Lisa; Dietrich, Susan; Dubinsky, Hilary; Eaton, Ken; Erickson, Diane; Fitzpatrick, Mary Jane; Frucht, Steven; Gartner, Maureen; Goldstein, Jody; Griffith, Jane; Hickey, Charlyne; Hunt, Victoria; Jaglin, Jeana; Klimek, Mary Lou; Lindsay, Pat; Louis, Elan; Loy, Clemet; Lucarelli, Nancy; Malarick, Keith; Martin, Amanda; McInnis, Robert; Moskowitz, Carol; Muratori, Lisa; Nucifora, Frederick; O'Neill, Christine; Palao, Alicia; Peavy, Guerry; Quesada, Monica; Schmidt, Amy; Segro, Vicki; Sperin, Elaine; Suter, Greg; Tanev, Kalo; Tempkin, Teresa; Thiede, Curtis; Wasserman, Paula; Welsh, Claire; Wesson, Melissa; Zauber, Elizabeth

    2012-01-01

    Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

  11. DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

    PubMed Central

    Bettencourt, Conceição; Hensman‐Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas‐Gómez, Petra; García‐Velázquez, Lizbeth Esmeralda; Alonso‐Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J.

    2016-01-01

    Objective The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. Methods We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. Results In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10–5). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10–5) and all SCAs (p = 2.22 × 10–4) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10–5), all in the same direction as in the HD GWAS. Interpretation We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983–990 PMID:27044000

  12. Chronic suppurative lung disease in adults

    PubMed Central

    Mangardich, Antranik

    2016-01-01

    Chronic suppurative lung disease (CSLD), characterized by a bronchiectasis-like syndrome in the absence of bronchial dilatation, is well described in the pediatric literature. In some patients, it may be a precursor of bronchiectasis. In adults, this syndrome has not been well described. We present four adult patients without obvious causative exposures who presented with prolonged cough and purulent sputum. Sputum cultures revealed a variety of Gram negative bacteria, fungi and mycobacteria. High resolution CT scanning did not reveal bronchiectasis. Evaluation revealed underlying causes including immunodeficiency in two, and Mycobacterium avium infection. One patient subsequently developed bronchiectasis. All patients improved with therapy. CSLD occurs in adults and has characteristics that distinguish it from typical chronic bronchitis. These include the lack of causative environmental exposures and infection with unusual pathogens. Evaluation and treatment of these patients similar to bronchiectasis patients may lead to clinical improvement. PMID:27747039

  13. Hepatosplenic Cat Scratch Disease in Immunocompetent Adults

    PubMed Central

    García, Juan C.; Núñez, Manuel J.; Castro, Begoña; Fernández, Jesús M.; Portillo, Aránzazu; Oteo, José A.

    2014-01-01

    Abstract Cat-scratch disease (CSD) is the most frequent presentation of Bartonella henselae infection. It has a worldwide distribution and is associated with a previous history of scratch or bite from a cat or dog. CSD affects children and teenagers more often (80%) than adults, and it usually has a self-limiting clinical course. Atypical clinical course or systemic symptoms are described in 5%–20% of patients. Among them, hepatosplenic (HS) forms (abscess) have been described. The majority of published cases have affected children or immunosuppressed patients. Few cases of HS forms of CSD in immunocompetent adult hosts have been reported, and data about the management of this condition are scarce. Herein, we present 3 new cases of HS forms of CSD in immunocompetent adults and review 33 other cases retrieved from the literature. We propose an approach to clinical diagnosis and treatment with oral azithromycin. PMID:25398062

  14. Long-Term Blood Pressure Variability, New-Onset Diabetes Mellitus, and New-Onset Chronic Kidney Disease in the Japanese General Population.

    PubMed

    Yano, Yuichiro; Fujimoto, Shouichi; Kramer, Holly; Sato, Yuji; Konta, Tsuneo; Iseki, Kunitoshi; Iseki, Chiho; Moriyama, Toshiki; Yamagata, Kunihiro; Tsuruya, Kazuhiko; Narita, Ichiei; Kondo, Masahide; Kimura, Kenjiro; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi

    2015-07-01

    Whether long-term blood pressure (BP) variability among individuals without diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk, independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and metabolic profile changes during follow-up, remains uncertain. We used data from a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7 years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m2 or proteinuria by dipstick). BP was measured at baseline and during 3 annual follow-up visits (4 visits). BP variability was defined as standard deviation (SD) and average real variability during the 4 visits. At the year 3 follow-up visit, 6.3% of the population had developed CKD. In multivariable-adjusted logistic regression models, 1 SD increases in SDSBP (per 5 mmHg), SDDBP (per 3 mmHg), average real variabilitySBP (per 6 mmHg), and average real variabilityDBP (per 4 mmHg) were associated with new-onset CKD (odds ratios [ORs] and 95% confidence intervals, 1.15 [1.11-1.20], 1.08 [1.04-1.12], 1.13 [1.09-1.17], 1.06 [1.02-1.10], respectively; all P<0.01) after adjustment for clinical characteristics, and with mean BP from year 0 to year 3. The associations of SDBP and average real variabilityBP with CKD remained significant after additional adjustments for metabolic parameter changes during follow-up (ORs, 1.06-1.15; all P<0.01). Sensitivity analyses by sex, antihypertensive medication use, and the presence of hypertension showed similar conclusions. Among those in the middle-aged and elderly general population without diabetes mellitus, long-term BP variability during 3 years was associated with new-onset CKD risk, independently of mean or cumulative exposure to BP and metabolic profile changes during follow-up.

  15. The APOE locus advances disease progression in late onset familial Alzheimer`s disease but is not causative

    SciTech Connect

    Crawford, F.; Bennett, C.; Osborne, A.

    1994-09-01

    An association has been observed in several independent data sets between late onset Alzheimer`s disease (AD) and the APOE locus on chromosomes 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the {epsilon}4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and nonstringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease-free survival suggested that APOE genotype contributes a small fraction of the total variance, indicating that the APOE locus is a poor predictor of disease-free survival time within late onset families. We suggest that the APOE locus enhances the rate of progression of the disease in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause this disease.

  16. Adult-onset hypogonadism: evaluation and role of testosterone replacement therapy

    PubMed Central

    Davidiuk, Andrew J.

    2016-01-01

    Testosterone deficiency (TD) has become a growing concern in the field of men’s sexual health, with an increasing number of men presenting for evaluation of this condition. Given the increasing demand for testosterone replacement therapy (TRT), a panel of experts met in August of 2015 to discuss the treatment of men who present for evaluation in the setting of low or normal gonadotropin levels and the associated signs and symptoms of hypogonadism. This constellation of factors can be associated with elements of both primary and secondary hypogonadism. Because this syndrome commonly occurs in men who are middle-aged and older, it was termed adult-onset hypogonadism (AOH). AOH can be defined by the following elements: low levels of testosterone, associated signs and symptoms of hypogonadism, and low or normal gonadotropin levels. Although there are significant benefits of TRT for patients with AOH, candidates also need to understand the potential risks. Patients undergoing TRT will need to be monitored regularly because there are potential complications that can develop with long-term use. This review is aimed at providing a deeper understanding of AOH, discussing the benefits and risks of TRT, and outlining each modality of TRT in use for AOH. PMID:28078213

  17. A search for the primary abnormality in adult-onset type II citrullinemia

    SciTech Connect

    Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori ); Kumashiro, Ryukichi; Tanikawa, Kyuichi ); O'Brien, W.E.; Beaudet, A.L. )

    1993-11-01

    Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.

  18. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    SciTech Connect

    Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

  19. Delayed diagnosis of late-onset Pompe disease in patients with myopathies of unknown origin and/or hyperCKemia.

    PubMed

    Pérez-López, Jordi; Selva-O'Callaghan, Albert; Grau-Junyent, Josep M; Gallego-Galindo, Luis; Coll, M Josep; García-Morillo, Salvador; Torralba-Cabeza, Miguel A; Vilardell-Tarrés, Miquel

    2015-04-01

    Pompe disease is a rare metabolic myopathy whose diagnosis is sometimes delayed despite being essential for improving clinical outcomes. We aimed to investigate the prevalence of late-onset Pompe disease among patients with a myopathy of unknown etiology, including polymyositis, or with idiopathic rise of creatine kinase (CK) levels, in a department of internal medicine. A cohort study was conducted in 241 subjects: 140 patients with myopathies of unknown origin or increased CK levels, 30 with polymyositis and 71 who constituted the control group of other myopathies. Acid α-glucosidase (GAA) activity was tested in dried blood spots. If a positive result was obtained, GAA activity in isolated lymphocytes and/or genetic testing was performed as a confirmatory diagnosis. Out of the 140 investigated patients, 2 patients with myopathies of unknown origin were confirmed to be positive for Pompe disease. Thus, late-onset Pompe disease should be considered among adult patients with myopathy of unknown origin.

  20. Striatal Volume Contributes to the Prediction of Onset of Huntington Disease in Incident Cases

    PubMed Central

    Aylward, Elizabeth H.; Liu, Dawei; Nopoulos, Peggy C.; Ross, Christopher A.; Pierson, Ronald K.; Mills, James A.; Long, Jeffrey D.; Paulsen, Jane S.

    2011-01-01

    Background Previous neuroimaging research indicates that brain atrophy in Huntington disease (HD) begins many years before movement abnormalities become severe enough to warrant diagnosis. Most clinical trials being planned for individuals in the prediagnostic stage of HD propose to use delay of disease onset as the primary outcome measure. Although formulae have been developed, based on age and CAG repeat length, to predict when HD motor onset will occur, it would be useful to have additional measures that can improve the accuracy of prediction of disease onset. Methods The current study examined MRI measures of striatum and white matter volume in 85 individuals prospectively followed from pre-HD stage through diagnosable motor onset (“incident cases”) and 85 individuals individually-matched with incident cases on CAG repeat length, sex, and age, who were not diagnosed with HD during the course of the study. Results Volumes of striatum and white matter were significantly smaller in individuals who would be diagnosed 1 to 4 years following the initial MRI scan, compared to those who would remain in the pre-HD stage. Putamen volume was the measure that best distinguished between the two groups. Conclusions Results suggest that MRI volumetric measures may be helpful in selecting individuals for future clinical trials in pre-HD where HD motor onset is the primary outcome measure. In planning for multisite clinical trials in pre-HD, investigators may also want to consider using more objective measures, such as MRI volumes, in addition to onset of diagnosable movement disorder, as major outcome measures. PMID:21907324

  1. The Phospholipase D2 Knock Out Mouse Has Ectopic Purkinje Cells and Suffers from Early Adult-Onset Anosmia

    PubMed Central

    Zhang, Qifeng; Smethurst, Elizabeth; Segonds-Pichon, Anne; Schrewe, Heinrich; Wakelam, Michael J. O.

    2016-01-01

    Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA), a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO) mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA) regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction. PMID:27658289

  2. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia linked CSF1R mutation: Report of four Korean cases.

    PubMed

    Kim, Eun-Joo; Shin, Jin-Hong; Lee, Jeong Hee; Kim, Jong Hun; Na, Duk L; Suh, Yeon-Lim; Hwang, Sun Jae; Lee, Jae-Hyeok; Lee, Young Min; Shin, Myung-Jun; Lee, Myung Jun; Kim, Seong-Jang; Yoon, Uicheul; Park, Do Youn; Jung, Dae Soo; Ahn, Jae Woo; Sung, Suk; Huh, Gi Yeong

    2015-02-15

    We describe detailed clinical, biochemical, neuroimaging and neuropathological features in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD), linked to colony-stimulating factor 1 receptor (CSF1R) mutations in four Korean cases. Clinical, biochemical, neuroimaging and neuropathological findings were obtained by direct evaluation and from previous medical records. The genetic analysis of the CSF1R gene was done in two autopsy-confirmed ALSP cases and two cases where ALSP was suspected based on the clinical and neuroimaging characteristics. We identified two known mutations: c.2342C>T (p.A781V) in one autopsy-proven HDLS and clinically ALSP-suspected case and c.2345G>A (p.R782H) in another autopsy-proven POLD case. We also found a novel mutation (c.2296A>G; p.M766V) in a patient presenting with hand tremor, stuttering and hesitant speech, and abnormal behavior whose father died from a possible diagnosis of spinocerebellar ataxia. To the best of our knowledge, this is the first documented ALSP-linked CSF1R mutation in Korea and supports the suggestion that HDLS and POLD, with pathological characteristics that are somewhat different but which are caused by CSF1R mutations, are the same spectrum of disease, ALSP.

  3. Adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia: report of a family, historical perspective, and review of the literature.

    PubMed

    Marotti, Jonathan D; Tobias, Sharon; Fratkin, Jonathan D; Powers, James M; Rhodes, C Harker

    2004-06-01

    We present a two-generation family consisting of a father and two daughters, who had an adult-onset leukodystrophy characterized by widespread destruction of cerebral white matter with neuroaxonal spheroids. The mode of inheritance appears to be autosomal dominant. All three patients presented with a variety of motor and cognitive symptoms, including frontal lobe signs, 4-7 years before death. Each followed a chronic course until death at ages 39, 46, and 51. At autopsy, the white matter loss was widespread but most prominent in the cerebrum with descending corticospinal tract degeneration and relative sparing of subcortical U-fibers. Pigmented glial cells were present, most of which appear to be macrophages, but inconstantly Prussian blue-positive. This disease is consistent with published reports of hereditary diffuse leukoencephalopathy with spheroids (HDLS). However, a review of the literature and a personal review of the neuropathology of the original case of the pigmentary type of orthochromatic leukodystrophy (POLD) reveal overlapping clinical and neuropathologic features between these two previously distinct entities, suggesting a common pathogenetic and perhaps etiological relationship between the two.

  4. Male predominance among Japanese adult patients with late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation.

    PubMed

    Asano, Y; Kanda, Y; Ogawa, N; Sakata-Yanagimoto, M; Nakagawa, M; Kawazu, M; Goyama, S; Kandabashi, K; Izutsu, K; Imai, Y; Hangaishi, A; Kurokawa, M; Tsujino, S; Ogawa, S; Aoki, K; Chiba, S; Motokura, T; Hirai, H

    2003-12-01

    Late-onset hemorrhagic cystitis (LHC) after hematopoietic stem cell transplantation (HSCT) is mainly caused by viral infections. We retrospectively analyzed the records of 141 Japanese adult patients who underwent a first allogeneic HSCT from 1995 to 2002. In all, 19 patients developed LHC a median of 51 days after HSCT. Adenovirus (AdV) was detected in the urine of 10 LHC patients, of whom eight had AdV type 11. Five of the six available serum samples from these patients were also positive for AdV type 11, but the detection of AdV in serum was not associated with a worse outcome. Male sex and the development of grade II-IV acute graft-versus-host disease were identified as independent significant risk factors for LHC. Male predominance was detected in LHC after HSCT, as has been previously shown in children with AdV-induced acute HC. The detection of AdV DNA in serum did not predict a poor outcome.

  5. Stroke in adult polycystic kidney disease.

    PubMed Central

    Rivera, M.; Gonzalo, A.; Gobernado, J. M.; Orte, L.; Quereda, C.; Ortuño, J.

    1992-01-01

    In order to assess the incidence of acute cerebrovascular events, 142 patients with adult polycystic kidney disease were retrospectively reviewed. Fourteen patients (9.8%) had 19 cerebral attacks. Six patients (4.2%) had intracranial haemorrhage attacks (three ruptured intracranial aneurysms and three cerebral haemorrhages). Ischaemic events occurred in nine patients (five cerebral infarctions and four transient ischaemic attacks). Patients with ischaemic attacks had a better outcome than patients with haemorrhagic events even when transient ischaemic attacks were excluded. Patients with ruptured intracranial aneurysms were younger. Cerebral complications are an important cause of morbidity and mortality in patients with adult polycystic kidney disease. They can prove disabling prior to or after dialysis and transplantation. PMID:1480536

  6. Adult Xanthogranulomatous Disease of the Orbit: Clinical Presentations, Evaluation, and Management.

    PubMed

    Ortiz Salvador, J M; Subiabre Ferrer, D; Pérez Ferriols, A

    2017-03-02

    Adult xanthogranulomatous disease of the orbit refers to a heterogeneous group of clinical syndromes with differing degrees of systemic involvement and distinct prognoses. The different syndromes all present clinically with progressively enlarging, yellowish lesions of the orbit. Histologically, the lesions are characterized by an inflammatory infiltrate of foam cells and Touton-type multinucleated giant cells. The xanthomatized histiocytes are CD68(+), S100(-), and CD1a(-). There are 4 clinical forms of xanthogranulomatous disease of the orbit: adult xanthogranulomatous disease of the orbit, adult onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. The treatment of local lesions are treated with systemic corticosteroids and other immunosuppressors. Vemurafenib, tocilizumab, and sirolimus have shown promising results in systemic disease.

  7. Clinical onset of celiac disease after duodenal switch: a case report.

    PubMed

    Pané, A; Orois, A; Careaga, M; Saco, A; Ortega, E; Vidal, J; Leyes, P; Amor, A J

    2016-09-01

    To our knowledge, this is the first reported case of clinical onset of celiac disease (CD) following duodenal switch surgery. A 61-year-old obese woman developed severe diarrhea soon after bariatric surgery (BS), which was unresponsive to standard medical treatment. After the most common diarrhea etiologies in the immediate postoperative period have been excluded, serological tests were performed. Final diagnosis was determined by anti-tissue transglutaminase antibody positivity. In light of this case report, we propose that CD should be ruled out in any patient presenting with typical or atypical symptoms after BS, regardless of the latency of onset.

  8. Relationship Between Longitudinal Measures of Renal Function and Onset of Dementia Among a Community Cohort of Older Adults

    PubMed Central

    O’Hare, Ann M.; Walker, Rod; Haneuse, Sebastian; Crane, Paul K.; McCormick, Wayne C.; Bowen, James D.; Larson, Eric B.

    2012-01-01

    Background Prior studies have described a higher incidence of dementia or worsening cognitive function in patients with lower levels of kidney function at a single point in time. Objectives To evaluate the association between dynamic measures of renal function ascertained over time with onset of dementia. Design prospective community cohort study. Setting and Participants 2,968 adults aged 65 and older followed for the development of dementia over a median of 6.0 years (interquartile range 3.1–10.1 years). Measurements Time varying measures of renal function were constructed based on a total of 49,340 serum creatinine measurements and included: the average level of estimated glomerular filtration rate (eGFR), eGFR trajectory and variability in eGFR around this trajectory over 5-year exposure windows. The association between these three eGFR exposure measures and risk of dementia was estimated using a Cox regression model adjusted for other patient characteristics. In sensitivity analyses, we also adjusted for time-varying measures of urine protein by dipstick. Results Patients with lower levels of eGFR had a higher incidence of dementia but this did not reach statistical significance in adjusted analyses (omnibus p value=0.14). There were trends toward a higher adjusted incidence of dementia in patients with positive eGFR trajectories (omnibus p value=0.07) and greater variability in eGFR (omnibus p value=0.04) over time. The results of sensitivity analyses, including those in which we included time-varying measures of proteinuria, were consistent with those of the primary analysis. Conclusion Among a community cohort of older adults followed for a median of 6 years, we did not find strong associations between measures of kidney disease severity and progression and incident dementia. PMID:23231548

  9. Novel parkin mutations detected in patients with early-onset Parkinson's disease.

    PubMed

    Bertoli-Avella, Aida M; Giroud-Benitez, José L; Akyol, Ali; Barbosa, Egberto; Schaap, Onno; van der Linde, Herma C; Martignoni, Emilia; Lopiano, Leonardo; Lamberti, Paolo; Fincati, Emiliana; Antonini, Angelo; Stocchi, Fabrizio; Montagna, Pasquale; Squitieri, Ferdinando; Marini, Paolo; Abbruzzese, Giovanni; Fabbrini, Giovanni; Marconi, Roberto; Dalla Libera, Alessio; Trianni, Giorgio; Guidi, Marco; De Gaetano, Antonio; Boff Maegawa, Gustavo; De Leo, Antonino; Gallai, Virgilio; de Rosa, Giulia; Vanacore, Nicola; Meco, Giuseppe; van Duijn, Cornelia M; Oostra, Ben A; Heutink, Peter; Bonifati, Vincenzo

    2005-04-01

    A multiethnic series of patients with early-onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype-genotype relationships. Forty-six EOP probands with an onset age of < 45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost-effective, real-time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11-3C > G, and exon 8-9-10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work-up of EOP.

  10. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders.

    PubMed

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions.

  11. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders

    PubMed Central

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary “myopathic” changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions. PMID:26999347

  12. Correlates of Age Onset of Type 2 Diabetes Among Relatively Young Black and White Adults in a Community

    PubMed Central

    Nguyen, Quoc Manh; Xu, Ji-Hua; Chen, Wei; Srinivasan, Sathanur R.; Berenson, Gerald S.

    2012-01-01

    OBJECTIVE The risk factors for middle-age onset of type 2 diabetes are well known. However, information is scant regarding the age onset of type 2 diabetes and its correlates in community-based black and white relatively young adults. RESEARCH DESIGN AND METHODS This prospective cohort study consisted of normoglycemic (n = 2,459) and type 2 diabetic (n = 144) adults aged 18–50 years who were followed for an average of 16 years. RESULTS The incidence rate of the onset of type 2 diabetes was 1.6, 4.3, 3.9, and 3.4 per 1,000 person-years for age-groups 18–29, 30–39, and 40–50 and total sample, respectively. Incidences of diabetes increased with age by race and sex groups (P for trend ≤0.01); higher in black females versus white females and blacks versus whites in total sample (P < 0.05). In a multivariable Cox model, baseline parental diabetes (hazard ratio [HR] 5.24) and plasma insulin were significantly associated with diabetes incidence at the youngest age (18–29 years); black race, BMI, and glucose at age 30–39 years; female sex, parental diabetes (HR 2.44), BMI, ratio of triglycerides and HDL cholesterol (TG/HDL-C ratio), and glucose at age 40–50 years; and black race, parental diabetes (HR 2.44), BMI, TG/HDL-C ratio, and glucose in whole cohort. Further, patients with diabetes, regardless of age onset, displayed a significantly higher prevalence of maternal history of diabetes at baseline (P < 0.01). CONCLUSIONS In relatively young adults, predictability of baseline cardiometabolic risk factors along with race, sex, and parental history of diabetes for the onset of type 2 diabetes varied by age-group. These findings have implications for early prevention and intervention in relatively young adults. PMID:22399694

  13. Onset and duration of protective immunity against clinical disease and renal carriage in dogs provided by a bi-valent inactivated leptospirosis vaccine.

    PubMed

    Minke, J M; Bey, R; Tronel, J P; Latour, S; Colombet, G; Yvorel, J; Cariou, C; Guiot, A L; Cozette, V; Guigal, P M

    2009-05-28

    Protection against clinical disease and prevention of the renal carrier state remain the key objectives of vaccination against leptospirosis in the dog. In the present paper, groups of dogs were vaccinated twice with a commercial bacterin (EURICAN L) containing Leptospira interrogans serovars icterohaemorrhagiae and canicola and challenged with heterologous representatives of both serovars at 2 weeks (onset of immunity) or 14 months (duration of immunity) after the second vaccination. Control dogs were not vaccinated against leptospirosis and kept with the vaccinated dogs. The challenges, irrespective of the serovar, reliably produced clinical signs consistent with Leptospira infection in the control pups with up to 60% mortality. As expected clinical disease in the adult controls was less severe, but we were able to induce morbidity and mortality as well. Under these extreme challenge conditions, clinical signs in the vaccinated dogs were rare, and when observed, mild and transient in nature. Following experimental infection, 100% of the control pups and 83% of the adult controls became renal carriers. Despite the heavy challenges, none of the 18 vaccinated puppies (onset of immunity studies) and only 2 out of the 16 vaccinated adult dogs (duration of immunity studies) developed a renal carrier state. These results show that a primary course of two doses of EURICAN L provided quick onset and long-term protection against both clinical leptospirosis and the renal carrier stage. This vaccine should provide veterinarians with a powerful tool to prevent clinical disease in dogs and zoonotic transmission of leptospirosis to humans.

  14. Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

    PubMed Central

    Hmida-Ben Brahim, Dorra; Chourabi, Marwa; Ben Amor, Sana; Harrabi, Imed; Trabelsi, Saoussen; Haddaji-Mastouri, Marwa; Gribaa, Moez; Sassi, Sihem; Gahbiche, Fatma Ezzahra; Lamouchi, Turkia; Mougou-Zereli, Soumaya; Ben Ammou, Sofiane; Saad, Ali

    2014-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population. PMID:25254119

  15. Complex movement disorders at disease onset in childhood narcolepsy with cataplexy

    PubMed Central

    Pizza, Fabio; Palaia, Vincenzo; Franceschini, Christian; Poli, Francesca; Moghadam, Keivan K.; Cortelli, Pietro; Nobili, Lino; Bruni, Oliviero; Dauvilliers, Yves; Lin, Ling; Edwards, Mark J.; Mignot, Emmanuel; Bhatia, Kailash P.

    2011-01-01

    Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of hypocretin-producing neurons in the hypothalamus of likely autoimmune aetiology. Noting that children with narcolepsy often display complex abnormal motor behaviours close to disease onset that do not meet the classical definition of cataplexy, we systematically analysed motor features in 39 children with narcolepsy with cataplexy in comparison with 25 age- and sex-matched healthy controls. We found that patients with narcolepsy with cataplexy displayed a complex array of ‘negative’ (hypotonia) and ‘active’ (ranging from perioral movements to dyskinetic–dystonic movements or stereotypies) motor disturbances. ‘Active’ and ‘negative’ motor scores correlated positively with the presence of hypotonic features at neurological examination and negatively with disease duration, whereas ‘negative’ motor scores also correlated negatively with age at disease onset. These observations suggest that paediatric narcolepsy with cataplexy often co-occurs with a complex movement disorder at disease onset, a phenomenon that may vanish later in the course of the disease. Further studies are warranted to assess clinical course and whether the associated movement disorder is also caused by hypocretin deficiency or by additional neurochemical abnormalities. PMID:21930661

  16. Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease.

    PubMed

    Aziz, Anne-Laure; Giusiano, Bernard; Joubert, Sven; Duprat, Lauréline; Didic, Mira; Gueriot, Claude; Koric, Lejla; Boucraut, José; Felician, Olivier; Ranjeva, Jean-Philippe; Guedj, Eric; Ceccaldi, Mathieu

    2017-02-21

    Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.

  17. Fifteen-year experience of pediatric-onset mixed connective tissue disease.

    PubMed

    Tsai, Yi-Ying; Yang, Yao-Hsu; Yu, Hsin-Hui; Wang, Li-Chieh; Lee, Jyh-Hong; Chiang, Bor-Luen

    2010-01-01

    The aim of this study was to investigate the initial clinical manifestations, laboratory data, complications, and outcomes of patients with pediatric-onset mixed connective tissue disease (MCTD) in Taiwan. We reviewed medical charts of patients younger than 18 years with a diagnosis of mixed connective tissue disease based on the criteria of Kasukawa (1) at the pediatric department of National Taiwan University Hospital from 1993 to 2008. A total of 12 patients were included. All of the patients were female. The mean age at disease onset was 10.7 years (range 6.5 to 14 years). The most common symptoms at disease onset were polyarthritis (7/12 patients) and Raynaud's phenomenon (7/12 patients). The clinical symptoms changed with time, and other symptoms encompassing the criteria for MCTD developed sequentially. Inflammatory manifestations (arthritis, fever, and skin rash) improved following treatment, whereas sclerodermatous features (sclerodactyly, esophageal disease, and vasculopathy) persisted and were often unresponsive to therapy. The organ involvement-free rates at 2 years, 5 years, and 10 years were 91.7%, 78.6%, and 52.4%, respectively. In this retrospective study, sclerodermatous changes of internal organs were a poor prognostic factor in our population, and we emphasize that long-term follow-up is necessary, and appropriate treatment should be applied to improve the outcomes.

  18. Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series

    PubMed Central

    Jaunmuktane, Zane; Sheerin, Una-Marie; Phadke, Rahul; Brandner, Sebastian; Milonas, Ionnis; Dean, Andrew; Bajaj, Nin; McNicholas, Nuala; Costello, Daniel; Cronin, Simon; McGuigan, Chris; Rossor, Martin; Fox, Nick; Murphy, Elaine; Chataway, Jeremy; Houlden, Henry

    2016-01-01

    Background Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene. Methods In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause. Results Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations. Conclusion We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia. PMID:25935893

  19. Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration

    PubMed Central

    Swaroop, Anand; Chew, Emily Y.; Rickman, Catherine Bowes; Abecasis, Gonçalo R.

    2012-01-01

    Aging-associated neurodegenerative diseases significantly influence the quality of life of affected individuals. Genetic approaches, combined with genomic technology, have provided powerful insights into common late-onset diseases, such as age-related macular degeneration (AMD). Here, we discuss current findings on the genetics of AMD to highlight areas of rapid progress and new challenges. We also attempt to integrate available genetic and biochemical data with cellular pathways involved in aging to formulate an integrated model of AMD pathogenesis. PMID:19405847

  20. Onset of Impaired Sleep and Cardiovascular Disease Risk Factors: A Longitudinal Study

    PubMed Central

    Clark, Alice Jessie; Salo, Paula; Lange, Theis; Jennum, Poul; Virtanen, Marianna; Pentti, Jaana; Kivimäki, Mika; Rod, Naja Hulvej; Vahtera, Jussi

    2016-01-01

    Study Objectives: Impaired sleep has been linked to increased risk of cardiovascular disease (CVD), but the underlying mechanisms are still unsettled. We sought to determine how onset of impaired sleep affects the risk of established physiological CVD risk factors (i.e., hypertension, diabetes, and dyslipidemia). Methods: In a longitudinal cohort study with 3 survey waves (2000, 2004, 2008) from the Finnish Public Sector study we used repeated information on sleep duration and disturbances to determine onset of impaired sleep. Information on development of CVD risk factors, as indicated by initiation of medication for hypertension, diabetes, and dyslipidemia was derived from electronic medical records within 8 years of follow-up. Data on 45,647 participants was structured as two data-cycles to examine the effect of change in sleep (between two waves) on incident CVD events. We applied strict inclusion and exclusion criteria to determine temporality between changes in sleep and the outcomes. Results: While we did not find consistent effects of onset of short or long sleep, we found onset of disturbed sleep to predict subsequent risk of hypertension (hazard ratio = 1.22, 95% CI: 1.04–1.44) and dyslipidemia (HR = 1.17, 95% CI: 1.07–1.29) in fully adjusted analyses. Conclusions: Results suggest that onset of sleep disturbances rather than short or long sleep mark an increase in physiological risk factors, which may partly explain the higher risk of CVD observed among impaired sleepers. Commentary: A commentary on this paper appears in this issue on page 1629. Citation: Clark AJ, Salo P, Lange T, Jennum P, Virtanen M, Pentti J, Kivimäki M, Rod NH, Vahtera J. Onset of impaired sleep and cardiovascular disease risk factors: a longitudinal study. SLEEP 2016;39(9):1709–1718. PMID:27397560

  1. Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

    PubMed Central

    Lee, Way Seah; Ng, Ruey Terng; Chan, Koon-Wing; Lau, Yu-Lung

    2016-01-01

    AIM Infantile-onset inflammatory bowel disease (IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10 (IL-10) and interleukin-10 receptors (IL-10R) in Asian children with IO-IBD. METHODS All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10R genes in patients with presenting clinical features of Crohn’s disease (CD). RESULTS Six [13%; CD = 3, ulcerative colitis (UC) = 2, IBD-unclassified (IBD-U) = 1] of the 48 children (CD = 25; UC = 23) with IBD have IO-IBD. At final review [median (range) duration of follow-up: 6.5 (3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy (IBD-U), after standard immunosuppression (CD), and after total colectomy (UC)]. Three patients were on immunosuppression: one (UC) was in remission while two (both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea (100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease (0% vs 19%, P = 0.31), requiring biologics therapy (50% vs 36%, P = 0.40), surgery (50% vs 29%, P = 0.27), or achieving remission (50% vs 64%, P = 0.40). No mutations in either IL10 or IL10R in the three patients with CD and the only patient with IBD-U were identified. CONCLUSION The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate. PMID:28082818

  2. A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study.

    PubMed

    Li, Jian-Liang; Hayden, Michael R; Almqvist, Elisabeth W; Brinkman, Ryan R; Durr, Alexandra; Dodé, Catherine; Morrison, Patrick J; Suchowersky, Oksana; Ross, Christopher A; Margolis, Russell L; Rosenblatt, Adam; Gómez-Tortosa, Estrella; Cabrero, David Mayo; Novelletto, Andrea; Frontali, Marina; Nance, Martha; Trent, Ronald J A; McCusker, Elizabeth; Jones, Randi; Paulsen, Jane S; Harrison, Madeline; Zanko, Andrea; Abramson, Ruth K; Russ, Ana L; Knowlton, Beth; Djoussé, Luc; Mysore, Jayalakshmi S; Tariot, Suzanne; Gusella, Michael F; Wheeler, Vanessa C; Atwood, Larry D; Cupples, L Adrienne; Saint-Hilaire, Marie; Cha, Jang-Ho J; Hersch, Steven M; Koroshetz, Walter J; Gusella, James F; MacDonald, Marcy E; Myers, Richard H

    2003-09-01

    Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.

  3. A Genome Scan for Modifiers of Age at Onset in Huntington Disease: The HD MAPS Study

    PubMed Central

    Li, Jian-Liang; Hayden, Michael R.; Almqvist, Elisabeth W.; Brinkman, Ryan R.; Durr, Alexandra; Dodé, Catherine; Morrison, Patrick J.; Suchowersky, Oksana; Ross, Christopher A.; Margolis, Russell L.; Rosenblatt, Adam; Gómez-Tortosa, Estrella; Cabrero, David Mayo; Novelletto, Andrea; Frontali, Marina; Nance, Martha; Trent, Ronald J. A.; McCusker, Elizabeth; Jones, Randi; Paulsen, Jane S.; Harrison, Madeline; Zanko, Andrea; Abramson, Ruth K.; Russ, Ana L.; Knowlton, Beth; Djoussé, Luc; Mysore, Jayalakshmi S.; Tariot, Suzanne; Gusella, Michael F.; Wheeler, Vanessa C.; Atwood, Larry D.; Cupples, L. Adrienne; Saint-Hilaire, Marie; Cha, Jang-Ho J.; Hersch, Steven M.; Koroshetz, Walter J.; Gusella, James F.; MacDonald, Marcy E.; Myers, Richard H.

    2003-01-01

    Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21–23 (LOD=2.29), and 6q24–26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD. PMID:12900792

  4. Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease)

    PubMed Central

    Staropoli, John F.; Carpenter, Stirling; Oliver, Karen L.; Kmoch, Stanislav; Anderson, Glenn W.; Damiano, John A.; Hildebrand, Michael S.; Sims, Katherine B.; Cotman, Susan L.; Bahlo, Melanie; Smith, Katherine R.; Cadieux-Dion, Maxime; Cossette, Patrick; Jedličková, Ivana; Přistoupilová, Anna; Mole, Sara E.

    2016-01-01

    Objective: To critically re-evaluate cases diagnosed as adult neuronal ceroid lipofuscinosis (ANCL) in order to aid clinicopathologic diagnosis as a route to further gene discovery. Methods: Through establishment of an international consortium we pooled 47 unsolved cases regarded by referring centers as ANCL. Clinical and neuropathologic experts within the Consortium established diagnostic criteria for ANCL based on the literature to assess each case. A panel of 3 neuropathologists independently reviewed source pathologic data. Cases were given a final clinicopathologic classification of definite ANCL, probable ANCL, possible ANCL, or not ANCL. Results: Of the 47 cases, only 16 fulfilled the Consortium's criteria of ANCL (5 definite, 2 probable, 9 possible). Definitive alternate diagnoses were made in 10, including Huntington disease, early-onset Alzheimer disease, Niemann-Pick disease, neuroserpinopathy, prion disease, and neurodegeneration with brain iron accumulation. Six cases had features suggesting an alternate diagnosis, but no specific condition was identified; in 15, the data were inadequate for classification. Misinterpretation of normal lipofuscin as abnormal storage material was the commonest cause of misdiagnosis. Conclusions: Diagnosis of ANCL remains challenging; expert pathologic analysis and recent molecular genetic advances revealed misdiagnoses in >1/3 of cases. We now have a refined group of cases that will facilitate identification of new causative genes. PMID:27412140

  5. 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.

  6. Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset.

    PubMed

    Chan, M K; Krebs, M-O; Cox, D; Guest, P C; Yolken, R H; Rahmoune, H; Rothermundt, M; Steiner, J; Leweke, F M; van Beveren, N J M; Niebuhr, D W; Weber, N S; Cowan, D N; Suarez-Pinilla, P; Crespo-Facorro, B; Mam-Lam-Fook, C; Bourgin, J; Wenstrup, R J; Kaldate, R R; Cooper, J D; Bahn, S

    2015-07-14

    Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95-1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86-0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71-0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82-0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset.

  7. Multipoint oligogenic analysis of age-at-onset data with applications to Alzheimer disease pedigrees.

    PubMed Central

    Daw, E W; Heath, S C; Wijsman, E M

    1999-01-01

    It is usually difficult to localize genes that cause diseases with late ages at onset. These diseases frequently exhibit complex modes of inheritance, and only recent generations are available to be genotyped and phenotyped. In this situation, multipoint analysis using traditional exact linkage analysis methods, with many markers and full pedigree information, is a computationally intractable problem. Fortunately, Monte Carlo Markov chain sampling provides a tool to address this issue. By treating age at onset as a right-censored quantitative trait, we expand the methods used by Heath (1997) and illustrate them using an Alzheimer disease (AD) data set. This approach estimates the number, sizes, allele frequencies, and positions of quantitative trait loci (QTLs). In this simultaneous multipoint linkage and segregation analysis method, the QTLs are assumed to be diallelic and to interact additively. In the AD data set, we were able to localize correctly, quickly, and accurately two known genes, despite the existence of substantial genetic heterogeneity, thus demonstrating the great promise of these methods for the dissection of late-onset oligogenic diseases. PMID:10053019

  8. [Adult-onset ataxia-telangiectasia. A clinical and therapeutic observation].

    PubMed

    Gazulla, J; Benavente, I; Sarasa Barrio, M

    2006-10-01

    A case of adult-onset ataxia-telangiectasia (AT) is presented, with debut at the age of 18 years and survival into the fourth decade. The clinical picture included cerebellar ataxia, distal weakness and hypopalesthesia in the lower limbs, oculomotor apraxia, dysarthria, and conjunctival telangiectasiae. Carcinoembrionic antigen was raised in plasma. MR imaging showed atrophy of the cerebellar vermis and thinning of the spinal cord. Deficiencies of gamma-aminobutyric acid and glutamate have been found in the cerebellar cortex in a case of AT. These were attributed to the loss of Purkinje cells and granule cells. In spite of some ataxias having improved with the gabaergic drugs gabapentin and tiagabine, the administration of gabapentin, acetazolamide and a placebo, did not benefit this patient. Pregabalin, 225 mg/day, ameliorated the ataxia unexpectedly, with further improvement after the addition of tiagabine. The authors suggest that the beneficial effect observed might have been due, either to the higher affinity of pregabalin towards alpha2-delta, a subtype of the alpha2-delta subunit which forms part of the voltage-gated calcium channel; either to the profusion of this subtype in the Purkinje cell layer, or to its larger capacity to let calcium into the neuron; or to the combination of these. These differences with gabapentin could explain the higher power of pregabalin in the stimulation of the cerebellar structures, thus justifying the improvement of ataxia in this case of AT. A synergistic effect with pregabalin is proposed as the cause of the improvement obtained with the addition of tiagabine.

  9. Mental health among young adults in prison: the importance of childhood-onset conduct disorder

    PubMed Central

    Anckarsäter, Henrik; Wallinius, Märta; Billstedt, Eva

    2017-01-01

    Background The psychiatric health burden of prisoners is substantial. However, there is a lack of high-quality studies of psychiatric disorders among young adults with a high risk of reoffending. Aims To investigate the lifetime prevalence of psychiatric disorders and use of mental health services among young male violent offenders and the impact of childhood-onset conduct disorder (COCD). Method A nationally representative cohort (n = 270, age 18–25) of male offenders was followed back in medical records and clinically assessed by gold standard methods. Lifetime prevalences are presented together with odds ratios (ORs) as risk estimates in relation to COCD. Results Previous use of psychiatric services among the participants was high but their lifetime psychiatric morbidity was even higher, with 93% meeting criteria for at least one Axis I disorder. The COCD group was overrepresented in most clinical categories and carried five times higher odds (OR = 5.1, 95% CI 2.0–12.8) of a psychotic disorder, three times higher odds (OR = 3.2, 95% CI 1.2–8.5) of a substance use disorder and two times higher odds of a mood disorder (OR = 2.3, 95% CI 1.3–4.0) or anxiety disorder (OR = 2.0, 95% CI 1.1–3.5). Conclusions The mental health burden is substantial among young violent offenders, and COCD is an important indicator of future mental health problems which must be a priority for public health efforts. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28357134

  10. Treatment of periodontal disease in older adults.

    PubMed

    Renvert, Stefan; Persson, G Rutger

    2016-10-01

    Within the next 40 years the number of older adults worldwide will more than double. This will impact periodontal treatment needs and presents a challenge to health-care providers and governments worldwide, as severe periodontitis has been reported to be the sixth most prevalent medical condition in the world. Older adults (≥ 80 years of age) who receive regular dental care retain more teeth than those who do not receive such care, but routine general dental care for these individuals is not sufficient to prevent the progression of periodontitis with the same degree of success as in younger individuals. There is a paucity of data on the efficacy of different periodontal therapies for older individuals. However, considering the higher prevalence of chronic medical conditions seen in older adults, it cannot be assumed that periodontal therapy will yield the same degree of success seen in younger individuals. Furthermore, medications can influence the status of the periodontium and the delivery of periodontal care. As an example, anticoagulant drugs are common among older patients and may be a contraindication to certain treatments. Newer anticoagulants will, however, facilitate surgical intervention in older patients. Furthermore, prescription medications taken for chronic conditions, such as osteoporosis and cardiovascular diseases, can affect the periodontium in a variety of ways. In summary, consideration of socio-economic factors, general health status and multiple-drug therapies will, in the future, be an important part of the management of periodontitis in older adults.

  11. Influence of environmental factors on the onset and course of inflammatory bowel disease

    PubMed Central

    Dutta, Amit Kumar; Chacko, Ashok

    2016-01-01

    Numerous environmental factors have been linked with inflammatory bowel disease. These include smoking, diet, hygiene, drugs, geographical and psychosocial factors. These factors may either increase the risk of or protect against developing this condition and can also affect the course of illness in a positive or negative manner. A number of studies have examined the influence of environmental factors on inflammatory bowel diseases as a whole as well as on ulcerative colitis and Crohn’s disease separately. As there are differences in the pathogenesis of ulcerative colitis and Crohn’s disease, the effect of environmental factors on their onset and course is not always similar. Some factors have shown a consistent association, while reports on others have been conflicting. In this article we discuss the current evidence on the roles of these factors on inflammatory bowel disease, both as causative/protective agents and as modifiers of disease course. PMID:26811649

  12. Influence of environmental factors on the onset and course of inflammatory bowel disease.

    PubMed

    Dutta, Amit Kumar; Chacko, Ashok

    2016-01-21

    Numerous environmental factors have been linked with inflammatory bowel disease. These include smoking, diet, hygiene, drugs, geographical and psychosocial factors. These factors may either increase the risk of or protect against developing this condition and can also affect the course of illness in a positive or negative manner. A number of studies have examined the influence of environmental factors on inflammatory bowel diseases as a whole as well as on ulcerative colitis and Crohn's disease separately. As there are differences in the pathogenesis of ulcerative colitis and Crohn's disease, the effect of environmental factors on their onset and course is not always similar. Some factors have shown a consistent association, while reports on others have been conflicting. In this article we discuss the current evidence on the roles of these factors on inflammatory bowel disease, both as causative/protective agents and as modifiers of disease course.

  13. Effects of enzyme replacement therapy on five patients with advanced late-onset glycogen storage disease type II: a 2-year follow-up study.

    PubMed

    Furusawa, Yoshihiko; Mori-Yoshimura, Madoka; Yamamoto, Toshiyuki; Sakamoto, Chikako; Wakita, Mizuki; Kobayashi, Yoko; Fukumoto, Yutaka; Oya, Yasushi; Fukuda, Tokiko; Sugie, Hideo; Hayashi, Yukiko K; Nishino, Ichizo; Nonaka, Ikuya; Murata, Miho

    2012-03-01

    We examined the efficacy of 2-year enzyme replacement therapy (ERT) using recombinant human α-glucosidase (GAA; Myozyme®) in five long-term ventilator-dependent adults and aged patients with advanced, late-onset glycogen storage disease type II (GSDII, also known as Pompe disease). Although all patients had advanced respiratory failure and were ventilator-dependent for more than 6 years, four showed obvious improvements in muscle strength, pulmonary function, and activities of daily living after ERT. Improvement in each parameter was more prominent in the first year than in the second year. Values in the second year were still significantly better than those at study entry and indicate stabilization in the clinical status of all patients. These results suggest that ERT continues to be effective in the second year of treatment even in patients suffering from advanced late-onset GSDII disease with severe respiratory failure.

  14. Solitary, adult-onset, intraosseous myofibroma of the finger: report of a case and review of literature.

    PubMed

    Ma, Yihong; Siegal, Gene P; Wei, Shi

    2015-09-01

    Myofibroma is a rare benign neoplasm of myofibroblastic origin. It typically occurs in the skin and subcutaneous tissues of the head and neck in infants and young children as multicentric lesions known as infantile myofibromatosis. Intraosseous myofibromas are very rare and are typically destructive lesions that predominantly affect craniofacial bones in the setting of myofibromatosis. Solitary, intraosseous myofibromas in adults are exceedingly rare. Herein, we report a myofibroma involving the middle phalanx of the right index finger in a 58-year-old man who presented with a pathologic fracture. Twelve other cases of adult-onset, intraosseous myofibroma were compiled from the English language literature and integrated with this report.

  15. Familial late-onset Alzheimer's disease: description of an Italian family with four affected siblings and one case of early-onset dementia in the preceding generation.

    PubMed

    Abbate, Carlo; Arosio, Beatrice; Cantatore, Alessandra; Viti, Niccolò; Giunco, Fabrizio; Bagarolo, Renzo; Nicolini, Paola; Gussago, Cristina; Ferri, Evelyn; Casati, Martina; Rossi, Paolo Dionigi; Casè, Alessandra; Bergamaschini, Luigi; Vergani, Carlo; Mari, Daniela

    2016-10-01

    We describe a family composed of six siblings, four of which affected by late-onset Alzheimer's disease (LOAD). We constructed the family pedigree, evaluated mutations usually associated with early-onset Alzheimer's disease (APP, PSEN1, PSEN2), and assessed polymorphisms in the apolipoprotein E (APOE) gene and in cytokine genes that we had previously found to be associated with a higher risk of LOAD (IL-10, IL-6, TNF-α). Results showed that all subjects carried one ε4 allele of the APOE gene and those with the earliest age of onset exhibited the AA (-1082) IL-10 and the CC (-174) IL-6 genotypes. The only male had a genetic profile which also included the A (-308) TNF-α allele. These data confirm the role of the APOE gene as genetic risk factor in LOAD, and suggest that the risk of developing AD may be governed by a "susceptibility profile" involving polymorphisms in inflammatory genes.

  16. Mutation analysis of sporadic early-onset Alzheimer's disease using the NeuroX array.

    PubMed

    Barber, Imelda S; Braae, Anne; Clement, Naomi; Patel, Tulsi; Guetta-Baranes, Tamar; Brookes, Keeley; Medway, Christopher; Chappell, Sally; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew; Hardy, John; Mann, David M; Morgan, Kevin

    2017-01-01

    We have screened sporadic early-onset Alzheimer's disease (sEOAD, n = 408) samples using the NeuroX array for known causative and predicted pathogenic variants in 16 genes linked to familial forms of neurodegeneration. We found 2 sEOAD individuals harboring a known causative variant in PARK2 known to cause early-onset Parkinson's disease; p.T240M (n = 1) and p.Q34fs delAG (n = 1). In addition, we identified 3 sEOAD individuals harboring a predicted pathogenic variant in MAPT (p.A469T), which has previously been associated with AD. It is currently unknown if these variants affect susceptibility to sEOAD, further studies would be needed to establish this. This work highlights the need to screen sEOAD individuals for variants that are more classically attributed to other forms of neurodegeneration.

  17. THE ROLE OF STRESS IN PERIODONTAL DISEASE PROGRESSION IN OLDER ADULTS.

    PubMed

    Salazar, Christian R

    2013-11-01

    Periodontal disease is characterized by chronic inflammation of the gingiva (gum tissues) caused by infection with anaerobic bacteria. In older adults, progression of disease can lead to tooth loss, inadequate nutritional intake, and a higher risk of other chronic conditions such as cardiovascular disease and diabetes mellitus. As the proportion of older adults continues to grow over time and rates of tooth loss decline, prevalence and severity of periodontal disease will increase. While much is known about risk factors for disease onset, gaps remain in our understanding of factors that could influence disease progression. Over the past few decades, stress has been implicated as a contributory factor. This review critically examines the epidemiological and laboratory evidence and describes a conceptual framework that could help move the research forward.

  18. Heterogeneous Depression Responses to Chronic Pain Onset among Middle-Aged Adults: A Prospective Study

    PubMed Central

    Zhu, Zhuoying; Galatzer-Levy, Isaac R.; Bonanno, George A.

    2014-01-01

    Studies on depression response to chronic pain are limited by lack of clarification of different forms of response patterns and cross-sectional measures. The current study examined heterogeneous long-term patterns of depression response to chronic pain onset using the mixture modeling technique. Depression symptoms prior to and following pain onset over a course of six years were charted in a nationally representative middle-aged sample. Four distinct depression symptom trajectories emerged. The resilience (72.0%) trajectory describes a pattern of no/minimal depression symptoms prior to and following pain onset. The post-pain depression trajectory (11.4%) describes a pattern of low depression at baseline and increasing symptoms following pain onset. The chronic depression (6.8%) trajectory is characterized by persistently high depression symptoms irrespective of pain onset. The prior depression improved (9.8%) trajectory describes a pattern of high depression at baseline and gradually declining symptoms following pain onset. Self-rated health at both baseline and following pain onset predicted the resilience trajectory. Baseline self-rated health distinguished the post-pain depression and chronic depression trajectories. Individuals in the prior depression improved trajectory were older and had more chronic illnesses at baseline but fewer illnesses following pain onset, compared to those in the resilience or post-pain depression trajectory. PMID:24679514

  19. Heart transplantation in adult congenital heart disease.

    PubMed

    Burchill, Luke J

    2016-12-01

    Heart failure (HF) in adult congenital heart disease (ACHD) is vastly different to that observed in acquired heart disease. Unlike acquired HF in which pharmacological strategies are the cornerstone for protecting and improving ventricular function, ACHD-related HF relies heavily upon structural and other interventions to achieve these aims. patients with ACHD constitute a small percentage of the total adult heart transplant population (∼3%), although the number of ACHD heart transplant recipients is growing rapidly with a 40% increase over the last two decades. The worldwide experience to date has confirmed heart transplantation as an effective life-extending treatment option in carefully selected patients with ACHD with end-stage cardiac disease. Opportunities for improving outcomes in patients with ACHD-related HF include (i) earlier recognition and referral to centres with combined expertise in ACHD and HF, (ii) increased awareness of arrhythmia and sudden cardiac death risk in this population, (iii) greater collaboration between HF and ACHD specialists at the time of heart transplant assessment, (iv) expert surgical planning to reduce ischaemic time and bleeding risk at the time of transplant, (v) tailored immunosuppression in the post-transplant period and (vi) development and validation of ACHD-specific risk scores to predict mortality and guide patient selection. The purpose of this article is to review current approaches to diagnosing and treating advanced HF in patients with ACHD including indications, contraindications and clinical outcomes after heart transplantation.

  20. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    SciTech Connect

    Lucotte, G.; David, F.; Berriche, S.

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  1. Motor onset and diagnosis in Huntington disease using the diagnostic confidence level.

    PubMed

    Liu, Dawei; Long, Jeffrey D; Zhang, Ying; Raymond, Lynn A; Marder, Karen; Rosser, Anne; McCusker, Elizabeth A; Mills, James A; Paulsen, Jane S

    2015-12-01

    Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine-adenine-guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington's Disease Rating Scale. HD progression from unimpaired to impaired motor function, as well as the progression from motor impairment to diagnosis, was associated with the linear effect of age and CAG repeat length. Specifically, for every 1-year increase in age, the risk of transition in diagnostic confidence level increased by 11% (95% CI 7-15%) and for one repeat length increase in CAG, the risk of transition in diagnostic confidence level increased by 47% (95% CI 27-69%). Findings show that CAG repeat length and age increased the likelihood of the first onset of motor impairment as well as the age at diagnosis. Results suggest that more accurate estimates of HD onset age can be obtained by incorporating the current status of diagnostic confidence level into predictive models.

  2. Neurofilaments in blood and CSF for diagnosis and prediction of onset in Creutzfeldt-Jakob disease

    PubMed Central

    Steinacker, Petra; Blennow, Kaj; Halbgebauer, Steffen; Shi, Song; Ruf, Viktoria; Oeckl, Patrick; Giese, Armin; Kuhle, Jens; Slivarichova, Dana; Zetterberg, Henrik; Otto, Markus

    2016-01-01

    While cerebrospinal fluid (CSF) biomarkers for Creutzfeldt-Jakob disease (CJD) are established and partly included in the diagnostic criteria, no blood biomarkers are available. Here, we assessed the utility of serum neurofilament light chain (NF-L) and tau protein in comparison to CSF markers (NF-L and phosphorylated NF heavy chain (pNF-H), tau, S100B, 14-3-3) and prion conversion assay (real-time quaking induced conversion (RT-QuIC)) for sporadic and genetic CJD. Importantly, a Gerstmann-Sträussler-Scheinker mutation carrier in the asymptomatic phase and at disease onset was included as well. Both NF-L and tau were markedly increased in CJD serum, reaching similar or even better performance as in CSF (sensitivity and specificity for serum NF-L 100% and 85.5%, and for serum tau 84.6% and 96.2%, respectively). Serum S100B showed high sensitivity as well (84.2%), but lower specificity (63%). CSF neurofilaments were increased before symptom onset, while prion seeding assay was negative. Just before a clinical diagnosis could be made, all CSF markers and NF-L in the serum were increased and CSF prion conversion assay was positive. The data suggest that neurofilaments are sensitive and specific blood markers for the diagnosis of genetic and sporadic CJD and might represent promising tools to predict disease onset. PMID:27929120

  3. A Systematic Review on the Implication of Minerals in the Onset, Severity and Treatment of Periodontal Disease.

    PubMed

    Varela-López, Alfonso; Giampieri, Francesca; Bullón, Pedro; Battino, Maurizio; Quiles, José L

    2016-09-07

    Periodontal disease is an inflammatory disease with high prevalence in adults that leads to destruction of the teeth-supporting tissues. Periodontal therapy has been traditionally directed at reduction of the bacterial load to a level that encourages health-promoting bacteria and maintenance of oral-hygiene. The role of nutrition in different chronic inflammatory diseases has been the subject of an increasing body of research in the last decades. In this sense, there has been an important increase in the volume of research on role of nutrition in periodontitis since the diet has known effects on the immune system and inflammatory cascades. Minerals play a key role in all these processes due to the multiple pathways where they participate. To clarify the role of the different minerals in the establishment, progression and/or treatment of this pathology, a systemically review of published literature cited in PubMed until May 2016 was conducted, which included research on the relationship of these elements with the onset and progression of periodontal disease. Among all the minerals, calcium dietary intake seems important to maintain alveolar bone. Likewise, dietary proportions of minerals that may influence its metabolism also can be relevant. Lastly, some observations suggest that all those minerals with roles in immune and/or antioxidant systems should be considered in future research.

  4. Altered PDE10A expression detectable early before symptomatic onset in Huntington's disease.

    PubMed

    Niccolini, Flavia; Haider, Salman; Reis Marques, Tiago; Muhlert, Nils; Tziortzi, Andri C; Searle, Graham E; Natesan, Sridhar; Piccini, Paola; Kapur, Shitij; Rabiner, Eugenii A; Gunn, Roger N; Tabrizi, Sarah J; Politis, Marios

    2015-10-01

    There is an urgent need for early biomarkers and novel disease-modifying therapies in Huntington's disease. Huntington's disease pathology involves the toxic effect of mutant huntingtin primarily in striatal medium spiny neurons, which highly express phosphodiesterase 10A (PDE10A). PDE10A hydrolyses cAMP/cGMP signalling cascades, thus having a key role in the regulation of striatal output, and in promoting neuronal survival. PDE10A could be a key therapeutic target in Huntington's disease. Here, we used combined positron emission tomography (PET) and multimodal magnetic resonance imaging to assess PDE10A expression in vivo in a unique cohort of 12 early premanifest Huntington's disease gene carriers with a mean estimated 90% probability of 25 years before the predicted onset of clinical symptoms. We show bidirectional changes in PDE10A expression in premanifest Huntington's disease gene carriers, which are associated with the probability of symptomatic onset. PDE10A expression in early premanifest Huntington's disease was decreased in striatum and pallidum and increased in motor thalamic nuclei, compared to a group of matched healthy controls. Connectivity-based analysis revealed prominent PDE10A decreases confined in the sensorimotor-striatum and in striatonigral and striatopallidal projecting segments. The ratio between higher PDE10A expression in motor thalamic nuclei and lower PDE10A expression in striatopallidal projecting striatum was the strongest correlate with higher probability of symptomatic conversion in early premanifest Huntington's disease gene carriers. Our findings demonstrate in vivo, a novel and earliest pathophysiological mechanism underlying Huntington's disease with direct implications for the development of new pharmacological treatments, which can promote neuronal survival and improve outcome in Huntington's disease gene carriers.

  5. Menkes disease – An important cause of early onset refractory seizures

    PubMed Central

    Jain, Puneet; Kannan, Lakshminarayanan; Chakrabarty, Biswaroop; Kumar, Atin; Gupta, Neerja; Kabra, Madhulika; Gulati, Sheffali

    2014-01-01

    Context: Menkes disease is an X-linked multisystem disorder characterized by early onset of cerebral and cerebellar neurodegeneration, fair skin, hypopigmented sparse hair and connective tissue abnormalities. Aims: We aimed to evaluate the clinical, electrophysiological and radiological features of children with Menkes disease seen at our institute. Setting/Design: The medical records of children diagnosed with Menkes disease admitted in the pediatric neurology ward or attending the special pediatric neurology clinic at a tertiary care and a referral hospital in North India, from January 2010 to December 2012, were retrospectively reviewed. The clinical data of each case was subsequently summarized and reported. Statistical analysis used: Descriptive statistics were used. Results: During the study period, 1174 children were seen. Out of these, 6 cases were diagnosed as Menkes disease on the basis of clinical phenotype, low serum copper and ceruloplasmin and supportive neuroimaging. All the children were males and had disease onset within 3 months of age, with 4 children presenting in the neonatal period. Global developmental delay and refractory seizures were the predominant clinical symptoms. Two children had symptomatic West syndrome. Other seizure semiologies included tonic-clonic (4), myoclonic (2) and tonic seizures (1). The electroencephalographic abnormalities included hypsarrythmia (2) and multifocal epileptiform discharges (3). The salient radiological features included white matter changes, temporal lobe abnormalities, global atrophy, subdural hygromas and tortuous cerebral blood vessels. Conclusions: Menkes disease should be suspected in a case of refractory early onset seizures especially in the presence of subtle clinical clues. The neuroimaging findings may further support the diagnosis. PMID:24891895

  6. A novel spatially-explicit condition for the onset of waterborne diseases in complex environments

    NASA Astrophysics Data System (ADS)

    Mari, L.; Gatto, M.; Bertuzzo, E.; Casagrandi, R.; Righetto, L.; Rodriguez-Iturbe, I.; Rinaldo, A.

    2012-12-01

    In spatial models of waterborne infections the condition that all the local reproduction numbers be larger than one is neither necessary nor sufficient for outbreaks to occur. Here, to properly determine epidemic onset conditions, we examine the transition from stable to unstable of the disease-free equilibrium of a system of nonlinear differential equations characterizing the evolution of susceptible and infected individuals within their respective settlements, and pathogen concentration in their accessible environment. Two different network connectivity layers are assumed to link human settlements: hydrologic pathways serve as ecological corridors for pathogens, while human mobility acts as disease vehicle through susceptibles contracting the disease and asymptomatic infectives shedding bacteria at their temporary destinations. We show that an epidemic outbreak can be triggered if the dominant eigenvalue of a generalized reproduction matrix G0, suitably accounting for spatial distribution of human settlements, hydrological pathways for pathogen dispersal and pathogen redistribution mechanisms due to human mobility, is larger than unity. Matrix G0 and its dominant eigenvalue thus replace the usual reproduction number whenever spatial effects on disease propagation cannot be ignored. Conversely, our novel criterion decays into the standard onset condition based on local reproduction numbers in nonspatial settings. By analyzing realistic test cases we show that within a connected network system the disease can start even if all the local reproduction numbers are smaller than unity, or might not start even if all the local reproduction numbers are larger than unity. We also show that onset geography in complex environments is linked to the dominant eigenvector of matrix G0. Applications to cholera outbreaks in developing countries demonstrate that our approach can be successfully used for disease prediction and emergency management.

  7. Lifestyle Risk Factors and New-Onset Diabetes Mellitus in Older Adults

    PubMed Central

    Mozaffarian, Dariush; Kamineni, Aruna; Carnethon, Mercedes; Djoussé, Luc; Mukamal, Kenneth J.; Siscovick, David

    2010-01-01

    Background The combined impact of lifestyle factors on incidence of diabetes mellitus later in life is not well established. The objective of this study was to determine how lifestyle factors, assessed in combination, relate to new-onset diabetes in a broad and relatively unselected population of older adults. Methods We prospectively examined associations of lifestyle factors, measured using repeated assessments later in life, with incident diabetes mellitus during a 10-year period (1989–1998) among 4883 men and women 65 years or older (mean [SD] age at baseline, 73[6] years) enrolled in the Cardiovascular Health Study. Low-risk lifestyle groups were defined by physical activity level (leisure-time activity and walking pace) above the median; dietary score (higher fiber intake and polyunsaturated to saturated fat ratio, lower trans-fat intake and lower mean glycemic index) in the top 2 quintiles; never smoked or former smoker more than 20 years ago or for fewer than 5 pack-years; alcohol use (predominantly light or moderate); body mass index less than 25 (calculated as weight in kilograms divided by height in meters squared); and waist circumference of 88 cm for women or 92 cm for men. The main outcome measure was incident diabetes defined annually by new use of insulin or oral hypoglycemic medications. We also evaluated fasting and 2-hour postchallenge glucose levels. Results During 34 539 person-years, 337 new cases of drug-treated diabetes mellitus occurred (9.8 per 1000 person-years). After adjustment for age, sex, race, educational level, and annual income, each lifestyle factor was independently associated with incident diabetes. Overall, the rate of incident diabetes was 35% lower (relative risk, 0.65; 95% confidence interval, 0.59–0.71) for each 1 additional lifestyle factor in the low-risk group. Participants whose physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes

  8. The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease

    SciTech Connect

    Yu, Chang-En; Nemens, E.; Olson, J.M.; Goddard, K.A.B.; Kukull, W.A.; Payami, H.; Boehnke, M.; Wijsman, E.M.; Orr, H.T.; White, J.A.

    1994-04-01

    The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset <60 years), and late-onset families. A genetic association was observed between apolipoprotein E (ApoE) allele E4 and FAD in late-onset families; the E4 allele frequency was .51 in affected subjects, .37 in at-risk subjects, .11 in spouses, and .19 in unrelated controls. The differences between the E4 frequencies in affected subjects versus controls and in at-risk subjects versus controls were highly significant. No association between the E4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between E4 and AD was also observed in a group of unrelated subjects; the E4 frequency was .26 in affected subjects, versus .19 in controls (Z[sub SND] = 2.20, P < .03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained. For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls or allele frequencies from the families were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased. For the ENVG group, results for ApoE and ApoCII were uniformly negative. Affected-pedigree-member analysis gave significant results for the late-onset kindreds, for ApoE, when control allele frequencies were used but not when allele frequencies were derived from the families. 58 refs., 6 tabs.

  9. The Apolipoprotein E/CI/CII Gene Cluster and Late-Onset Alzheimer Disease

    PubMed Central

    Yu, Chang-En; Payami, Haydeh; Olson, Jane M.; Boehnke, Michael; Wijsman, Ellen M.; Orr, Harry T.; Kukull, Walter A.; Goddard, Katrina A. B.; Nemens, Ellen; White, June A.; Alonso, M. Elisa; Taylor, Todd D.; Ball, Melvyn J.; Kaye, Jeffrey; Morris, John; Chui, Helena; Sadovnick, Adele D.; Martin, George M.; Larson, Eric B.; Heston, Leonard L.; Bird, Thomas D.; Schellenberg, Gerard D.

    1994-01-01

    The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset <60 years), and late-onset families. A genetic association was observed between apolipoprotein E (ApoE) allele ε4 and FAD in late-onset families; the ε4 allele frequency was .51 in affected subjects, .37 in at-risk subjects, .11 in spouses, and .19 in unrelated controls. The differences between the ε4 frequencies in affected subjects versus controls and in at-risk subjects versus controls were highly significant (standard normal deviate [ZSND]) = 7.37, P < 10−9; and ZSND = 4.07, P < .00005, respectively). No association between the ε4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between ε4 and AD was also observed in a group of unrelated subjects; the ε4 frequency was .26 in affected subjects, versus .19 in controls (ZSND = 2.20, P < .03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained (model 1, maximum Z [Zmax] = 0.61, recombination fraction [θ] = .30; model 2, Zmax = 0.47, θ = .20). For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls (model 1, Zmax = 2.02, θ = .15; model 2, Zmax = 3.42, θ = .05) or allele frequencies from the families (model 1, Zmax = 1.43, θ = .15; model 2, Zmax = 1.70, θ = .05) were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased (model 1, Zmax = 3.17,

  10. Identification of genetic modifiers of age-at-onset for familial Parkinson’s disease

    PubMed Central

    Hill-Burns, Erin M.; Ross, Owen A.; Wissemann, William T.; Soto-Ortolaza, Alexandra I.; Zareparsi, Sepideh; Siuda, Joanna; Lynch, Timothy; Wszolek, Zbigniew K.; Silburn, Peter A.; Mellick, George D.; Ritz, Beate; Scherzer, Clemens R.; Zabetian, Cyrus P.; Factor, Stewart A.; Breheny, Patrick J.; Payami, Haydeh

    2016-01-01

    Parkinson’s disease (PD) is the most common cause of neurodegenerative movement disorder and the second most common cause of dementia. Genes are thought to have a stronger effect on age-at-onset of PD than on risk, yet there has been a phenomenal success in identifying risk loci but not age-at-onset modifiers. We conducted a genome-wide study for age-at-onset. We analysed familial and non-familial PD separately, per prior evidence for strong genetic effect on age-at-onset in familial PD. GWAS was conducted in 431 unrelated PD individuals with at least one affected relative (familial PD) and 1544 non-familial PD from the NeuroGenetics Research Consortium (NGRC); an additional 737 familial PD and 2363 non-familial PD were used for replication. In familial PD, two signals were detected and replicated robustly: one mapped to LHFPL2 on 5q14.1 (PNGRC = 3E-8, PReplication = 2E-5, PNGRC + Replication = 1E-11), the second mapped to TPM1 on 15q22.2 (PNGRC = 8E-9, PReplication = 2E-4, PNGRC + Replication = 9E-11). The variants that were associated with accelerated onset had low frequencies (<0.02). The LHFPL2 variant was associated with earlier onset by 12.33 [95% CI: 6.2; 18.45] years in NGRC, 8.03 [2.95; 13.11] years in replication, and 9.79 [5.88; 13.70] years in the combined data. The TPM1 variant was associated with earlier onset by 15.30 [8.10; 22.49] years in NGRC, 9.29 [1.79; 16.79] years in replication, and 12.42 [7.23; 17.61] years in the combined data. Neither LHFPL2 nor TPM1 was associated with age-at-onset in non-familial PD. LHFPL2 (function unknown) is overexpressed in brain tumours. TPM1 encodes a highly conserved protein that regulates muscle contraction, and is a tumour-suppressor gene. PMID:27402877

  11. Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

    PubMed Central

    2010-01-01

    Background The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity. Methods We initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity. Results The trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05). Conclusions As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the

  12. A Potential Role of Salmonella Infection in the Onset of Inflammatory Bowel Diseases

    PubMed Central

    Schultz, Bárbara M.; Paduro, Carolina A.; Salazar, Geraldyne A.; Salazar-Echegarai, Francisco J.; Sebastián, Valentina P.; Riedel, Claudia A.; Kalergis, Alexis M.; Alvarez-Lobos, Manuel; Bueno, Susan M.

    2017-01-01

    Inflammatory bowel disease (IBD) includes a set of pathologies that result from a deregulated immune response that may affect any portion of the gastrointestinal tract. The most prevalent and defined forms of IBD are Crohn’s disease and ulcerative colitis. Although the etiology of IBD is not well defined, it has been suggested that environmental and genetic factors contribute to disease development and that the interaction between these two factors can trigger the pathology. Diet, medication use, vitamin D status, smoking, and bacterial infections have been proposed to influence or contribute to the onset or development of the disease in susceptible individuals. The infection with pathogenic bacteria is a key factor that can influence the development and severity of this disease. Here, we present a comprehensive review of studies performed in human and mice susceptible to IBD, which supports the notion that infection with bacterial pathogens, such as Salmonella, could promote the onset of IBD due to permanent changes in the intestinal microbiota, disruption of the epithelial barrier and alterations of the intestinal immune response after infection. PMID:28293241

  13. Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults

    PubMed Central

    Mozaffarian, Dariush; Cao, Haiming; King, Irena B.; Lemaitre, Rozenn N.; Song, Xiaoling; Siscovick, David S.; Hotamisligil, Gökhan S.

    2011-01-01

    Background Palmitoleic acid (cis-16:1n-7), produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative. Objective We investigated whether circulating trans-palmitoleate was independently related to lower metabolic risk and incident type2 diabetes. Design Prospective cohort study (1992–2006). Setting Four US communities. Patients 3,736 adults in the Cardiovascular Health Study. Measurements Plasma phospholipid fatty acids, anthropometry, blood lipids, inflammatory markers, and glucose-insulin levels were measured at baseline in 1992; and diet, 3 years earlier. In multivariable-adjusted models, we investigated how demographic, clinical, and lifestyle factors independently related to trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). We validated findings for metabolic risk factors in an independent cohort of 327 women. Results In multivariable-analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate. Higher trans-palmitoleate was associated with slightly lower adiposity and, independently, higher high-density-lipoprotein(HDL)-cholesterol (across quintiles: +1.9%, P=0.04), lower triglycerides (−19.0%, P<0.001), lower total:HDL-cholesterol (−4.7%, P<0.001), lower C-reactive protein (−13.8%, P=0.05), and lower insulin resistance (−16.7%, P<0.001). Trans-palmitoleate was associated with substantially lower incidence of diabetes, with multivariable-hazard-ratios=0.41 (95%CI=0.27–0.64) and 0.38 (95%CI=0.24–0.62) in quintile-4 and quintile-5, versus quintile-1 (P-trend<0.001). Findings were

  14. Allele doses of apolipoprotein E type {epsilon}4 in sporadic late-onset Alzheimer`s disease

    SciTech Connect

    Lucotte, G.; Aouizerate, A.; Gerard, N.

    1995-12-18

    Apoliprotein E, type {epsilon}4 allele (ApoE-{epsilon}4) is associated with late-onset sporadic Alzheimer`s disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-{epsilon}4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging. 26 refs., 2 figs., 1 tab.

  15. Adult-onset type 1 diabetes patients display decreased IGRP-specific Tr1 cells in blood.

    PubMed

    Chujo, Daisuke; Nguyen, Thien-Son; Foucat, Emile; Blankenship, Derek; Banchereau, Jacques; Nepom, Gerald T; Chaussabel, Damien; Ueno, Hideki

    2015-12-01

    The breakdown of immune tolerance against islet antigens causes type 1 diabetes (T1D). The antigens associated with adult-onset T1D (AT1D) remain largely undefined. It is possible that AT1D patients display a unique type of CD4(+) T cells specific for a certain islet antigen. Here we analyzed the cytokine production profiles of CD4(+) helper T (Th) cells that are specific for three islet antigens; GAD65, preproinsulin, and IGRP in patients with AT1D, juvenile-onset T1D (JT1D), and age-, gender- and human leukocyte antigen (HLA)-matched control adults. While IGRP-specific Th cells in AT1D patients were dominantly Th1 cells, IGRP-specific Th cells in control adults and JT1D patients were dominantly Th2 and T regulatory type 1 (Tr1) cells. Notably, the frequency of IGRP-specific Tr1 cells was significantly lower in AT1D patients than in control adults and JT1D patients. In conclusion, our study suggests that IGRP-specific Th cells play a unique pathogenic role in AT1D.

  16. Associations of clinical features and prognosis with age at disease onset in patients with systemic lupus erythematosus.

    PubMed

    Feng, X; Zou, Y; Pan, W; Wang, X; Wu, M; Zhang, M; Tao, J; Zhang, Y; Tan, K; Li, J; Chen, Z; Ding, X; Qian, X; Da, Z; Wang, M; Sun, L

    2014-03-01

    The objective of this study is to evaluate the association of clinical features and prognosis with age at disease onset in patients with systemic lupus erythematosus (SLE) in a large, multicenter Chinese cohort. Medical records of 1898 SLE inpatients from 15 hospitals were reviewed and classified into three groups according to their ages at disease presentation. Categorical data were analyzed by chi-square test and potentially associated factors were tested by multinomial logistic regression. Among the patients studied, 259 (13.6%) were juvenile onset (≤18 years), 1444 (76.1%) were early onset (>18 and ≤45 years) and 195 (10.3%) were late onset (>45 years). Whenever manifestations occurred, most patients (>80%) were diagnosed within two years. Juvenile-onset patients were more likely to be untreated before admission (p < 0.001) and have mucocutaneous manifestations (p < 0.001), but musculoskeletal symptoms (p < 0.05) and leukopenia (p < 0.05) were less frequent, while comorbidities were much higher in patients with late-onset SLE (p < 0.001). Neuropsychiatric, cardiopulmonary, renal and gastrointestinal involvement, disease activity index and damage scores were similar among three groups. Anti-Sm antibodies were less prevalent in late-onset patients (p < 0.05) and antimalarial drugs were more often applied to juvenile-onset patients (p < 0.001). As expected, mortality was elevated in the late-onset SLE group (p < 0.05), in which nearly half died of infections, which was much higher than those in the other two groups (p < 0.001). Logistic regression confirmed that patients with juvenile- and early-onset disease were associated with high incidence of being untreated prior to admission, and with low incidence of comorbidities as well as deaths caused by infection compared to patients with late-onset lupus. Interestingly, our data showed that more patients with late-onset disease had a SLEDAI score change of >7 at discharge. In

  17. Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

    PubMed Central

    Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

    2016-01-01

    Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

  18. Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled

    PubMed Central

    Li, Yi-Ju; Scott, William K.; Hedges, Dale J.; Zhang, Fengyu; Gaskell, P. Craig; Nance, Martha A.; Watts, Ray L.; Hubble, Jean P.; Koller, William C.; Pahwa, Rajesh; Stern, Matthew B.; Hiner, Bradley C.; Jankovic, Joseph; Allen, Jr., Fred H.; Goetz, Christopher G.; Mastaglia, Frank; Stajich, Jeffrey M.; Gibson, Rachel A.; Middleton, Lefkos T.; Saunders, Ann M.; Scott, Burton L.; Small, Gary W.; Nicodemus, Kristin K.; Reed, Allison D.; Schmechel, Donald E.; Welsh-Bohmer, Kathleen A.; Conneally, P. Michael; Roses, Allen D.; Gilbert, John R.; Vance, Jeffery M.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

    2002-01-01

    To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between 40%–60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases. PMID:11875758

  19. The treatment-naive microbiome in new-onset Crohn's disease.

    PubMed

    Gevers, Dirk; Kugathasan, Subra; Denson, Lee A; Vázquez-Baeza, Yoshiki; Van Treuren, Will; Ren, Boyu; Schwager, Emma; Knights, Dan; Song, Se Jin; Yassour, Moran; Morgan, Xochitl C; Kostic, Aleksandar D; Luo, Chengwei; González, Antonio; McDonald, Daniel; Haberman, Yael; Walters, Thomas; Baker, Susan; Rosh, Joel; Stephens, Michael; Heyman, Melvin; Markowitz, James; Baldassano, Robert; Griffiths, Anne; Sylvester, Francisco; Mack, David; Kim, Sandra; Crandall, Wallace; Hyams, Jeffrey; Huttenhower, Curtis; Knight, Rob; Xavier, Ramnik J

    2014-03-12

    Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.

  20. Age at onset in two common neurodegenerative diseases is genetically controlled.

    PubMed

    Li, Yi-Ju; Scott, William K; Hedges, Dale J; Zhang, Fengyu; Gaskell, P Craig; Nance, Martha A; Watts, Ray L; Hubble, Jean P; Koller, William C; Pahwa, Rajesh; Stern, Matthew B; Hiner, Bradley C; Jankovic, Joseph; Allen, Fred A; Goetz, Christopher G; Mastaglia, Frank; Stajich, Jeffrey M; Gibson, Rachel A; Middleton, Lefkos T; Saunders, Ann M; Scott, Burton L; Small, Gary W; Nicodemus, Kristin K; Reed, Allison D; Schmechel, Donald E; Welsh-Bohmer, Kathleen A; Conneally, P Michael; Roses, Allen D; Gilbert, John R; Vance, Jeffery M; Haines, Jonathan L; Pericak-Vance, Margaret A

    2002-04-01

    To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between 40%--60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases.

  1. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression

    PubMed Central

    Musumeci, Giuseppe; Aiello, Flavia Concetta; Szychlinska, Marta Anna; Di Rosa, Michelino; Castrogiovanni, Paola; Mobasheri, Ali

    2015-01-01

    Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by “low-grade inflammation” in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder. PMID:25785564

  2. Early-onset Alzheimer’s Disease: Nonamnestic Subtypes and Type 2 AD

    PubMed Central

    Mendez, Mario F.

    2012-01-01

    Patients with Alzheimer’s disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ~4–5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer’s research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22–64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein E ε4 (APOE ε4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. PMID:23178565

  3. Characterization of forebrain neurons derived from late-onset Huntington's disease human embryonic stem cell lines

    PubMed Central

    Niclis, Jonathan C.; Pinar, Anita; Haynes, John M.; Alsanie, Walaa; Jenny, Robert; Dottori, Mirella; Cram, David S.

    2012-01-01

    Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin (HTT) gene. Recently, induced pluripotent stem cell (iPSC) lines carrying atypical and aggressive (CAG60+) HD variants have been generated and exhibit disparate molecular pathologies. Here we investigate two human embryonic stem cell (hESC) lines carrying CAG37 and CAG51 typical late-onset repeat expansions in comparison to wildtype control lines during undifferentiated states and throughout forebrain neuronal differentiation. Pluripotent HD lines demonstrate growth, viability, pluripotent gene expression, mitochondrial activity and forebrain specification that is indistinguishable from control lines. Expression profiles of crucial genes known to be dysregulated in HD remain unperturbed in the presence of mutant protein and throughout differentiation; however, elevated glutamate-evoked responses were observed in HD CAG51 neurons. These findings suggest typical late-onset HD mutations do not alter pluripotent parameters or the capacity to generate forebrain neurons, but that such progeny may recapitulate hallmarks observed in established HD model systems. Such HD models will help further our understanding of the cascade of pathological events leading to disease onset and progression, while simultaneously facilitating the identification of candidate HD therapeutics. PMID:23576953

  4. Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing.

    PubMed

    Dinwiddie, Darrell L; Bracken, Julia M; Bass, Julie A; Christenson, Kathy; Soden, Sarah E; Saunders, Carol J; Miller, Neil A; Singh, Vivekanand; Zwick, David L; Roberts, Charles C; Dalal, Jignesh; Kingsmore, Stephen F

    2013-01-01

    Pediatric-onset inflammatory bowel disease (IBD) is known to be associated with severe disease, poor response to therapy, and increased morbidity and mortality. We conducted exome sequencing of two brothers from a non-consanguineous relationship who presented before the age of one with severe infantile-onset IBD, failure to thrive, skin rash, and perirectal abscesses refractory to medical management. We examined the variants discovered in all known IBD-associated and primary immunodeficiency genes in both siblings. The siblings were identified to harbor compound heterozygous mutations in IL10RA (c.784C>T, p.Arg262Cys; c.349C>T, p.Arg117Cys). Upon molecular diagnosis, the proband underwent successful hematopoietic stem cell transplantation and demonstrated marked clinical improvement of all IBD-associated clinical symptoms. Exome sequencing can be an effective tool to aid in the molecular diagnosis of pediatric-onset IBD. We provide additional evidence of the safety and benefit of HSCT for patients with IBD due to mutations in the IL10RA gene.

  5. Anxiety disorders and onset of cardiovascular disease: the differential impact of panic, phobias and worry.

    PubMed

    Batelaan, Neeltje M; ten Have, Margreet; van Balkom, Anton J L M; Tuithof, Marlous; de Graaf, Ron

    2014-03-01

    Anxiety has been linked to onset of cardiovascular disease. This study examines the differential impact of types of anxiety (panic, phobia and worry) on 3-year onset of non-fatal cardiovascular disease (CVD). By investigating anxiety disorders as opposed to anxiety symptoms and by using a reliable diagnostic instrument to assess anxiety, limitations of previous studies are considered. 5149 persons at risk for CVD were interviewed using the Composite International Diagnostic Interview. The panic-type included panic disorder and panic attacks; the phobic-type included agoraphobia and social phobia, and the worry-type included generalized anxiety disorder. CVD was self-reported and required treatment or monitoring by a doctor. Analyses were adjusted for sociodemographics, behavioral variables, and comorbid somatic and psychiatric disorders. During follow-up, 62 persons (1.2%) developed CVD. Baseline generalized anxiety disorder was strongly associated with onset of CVD (adjusted OR: 3.39). Further research should replicate findings and focus on biological underpinnings of this association.

  6. Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin

    PubMed Central

    Jeyakumar, Mylvaganam; Butters, Terry D.; Cortina-Borja, Mario; Hunnam, Victoria; Proia, Richard L.; Perry, V. Hugh; Dwek, Raymond A.; Platt, Frances M.

    1999-01-01

    Sandhoff disease is a neurodegenerative disorder resulting from the autosomal recessive inheritance of mutations in the HEXB gene, which encodes the β-subunit of β-hexosaminidase. GM2 ganglioside fails to be degraded and accumulates within lysosomes in cells of the periphery and the central nervous system (CNS). There are currently no therapies for the glycosphingolipid lysosomal storage diseases that involve CNS pathology, including the GM2 gangliosidoses. One strategy for treating this and related diseases is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which currently is in clinical trials for the potential treatment of type 1 Gaucher disease, a related disease that involves glycosphingolipid storage in peripheral tissues, but not in the CNS. In this study, we have evaluated whether this drug also could be applied to the treatment of diseases with CNS storage and pathology. We therefore have treated a mouse model of Sandhoff disease with the inhibitor N-butyldeoxynojirimycin. The treated mice have delayed symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offers a potentially general therapy for this family of lysosomal storage diseases, including those with CNS disease. PMID:10339597

  7. Intrathecal antibody production against Epstein-Barr and other neurotropic viruses in pediatric and adult onset multiple sclerosis.

    PubMed

    Pohl, Daniela; Rostasy, Kevin; Jacobi, Christian; Lange, Peter; Nau, Roland; Krone, Bernd; Hanefeld, Folker

    2010-02-01

    Epstein-Barr virus (EBV) has been implicated in the pathogenesis of multiple sclerosis (MS). Recent reports proposed an increased EBV-targeted humoral immune response in MS, which appears to be more pronounced in pediatric patients. However, little is known about the CNS-derived antibody production against EBV in patients with MS. The objective of this study was to assess the frequency and intensity of intrathecal antibody production against EBV as compared to other neurotropic viruses in pediatric and adult onset MS. In cohorts of 43 childhood, 50 adult onset MS patients, 20 children and 12 adults with other CNS disorders, paired CSF and serum samples were studied. Frequency and intensity of intrathecal antibody production against EBV as compared to measles, rubella, varicella zoster (VZV) and herpes simplex virus (HSV) were analyzed by determination of virus-specific CSF-to-serum Antibody Indices (AI). Intrathecally synthesized EBV antibodies were detectable in 26% pediatric and 10% adult onset MS patients, compared to frequencies ranging in both groups from 10 to 60% for the other viruses. Median AIs for EBV were lower than those for all other viruses, with more than twofold higher median AI for measles, rubella and VZV. The EBV-targeted humoral immune response in the CNS is only part of the intrathecal polyspecific antibody production in MS, directed against various neurotropic viruses. Our results do not rule out the possibility that EBV is involved in the pathogenesis of MS by triggering diverse cellular immune mechanisms, but they argue against a direct pathogenic role of EBV-targeted humoral immune response within the CNS.

  8. Obesity-related abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D.

    PubMed

    Nguyen, K Hoa; Ande, Sudharsana R; Mishra, Suresh

    2016-01-29

    The incidence of adult-onset T1D in low-risk non-HLA type has increased several folds, whereas the contemporaneous incidence in high-risk HLA-type remains stable. Various factors behind this selective increase in T1D in young adults remain unclear. Obesity and its associated abnormalities appear to be an important determinant; however, the underlying mechanism involved is not understood. Recently, we have developed two novel transgenic obese mice models, Mito-Ob and m-Mito-Ob, by expressing a pleiotropic protein prohibitin (PHB) and a phospho mutant form of PHB (Y114F-PHB or m-PHB) from the aP2 gene promoter, respectively. Both mice models develop obesity in a sex-neutral manner, independent of diet; but obesity associated chronic low-grade inflammation and insulin resistance in a male sex-specific manner. Interestingly, on a high fat diet (HFD) only male m-Mito-Ob mice displayed marked mononuclear cell infiltration in pancreas and developed insulitis that mimic adult-onset T1D. Male Mito-Ob mice that share the metabolic phenotype of male m-Mito-Ob mice, and female m-Mito-Ob that harbor m-PHB similar to male m-Mito-Ob mice, did not develop insulitis. Thus, insulitis development in male m-Mito-Ob in response to HFD requires both, obesity-related abnormalities and m-PHB. Collectively, this data provides a proof-of-concept that obesity-associated abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D and reveals PHB as a potential susceptibility gene for T1D.

  9. Age at onset in Huntington's disease: effect of line of inheritance and patient's sex.

    PubMed Central

    Roos, R A; Vegter-van der Vlis, M; Hermans, J; Elshove, H M; Moll, A C; van de Kamp, J J; Bruyn, G W

    1991-01-01

    The Leiden Roster for Huntington's disease (HD) contained data on 2617 cases up to July 1988. The age at onset (AO) was known in 1084 cases and in 1020 of these both their AO and the sex of the affected parent was known. The mean AO was higher for females than for males and higher for maternal than for paternal cases. However, in the group born before 1925 only females with maternal inheritance had a higher mean AO. Data on influence of sex and line of inheritance were present for the grandparents as well as for the great grandparents. Influence of the line of inheritance from the grandparents was particularly present for the grandmother-father (MP) lineage; regarding the great grandparents a significant difference was found between the MPM and PMP lineage. The results obtained for juvenile HD cases were comparable to those previously published. In late onset cases (over 50 years) no maternal preponderance in inheritance was found. PMID:1833547

  10. Acute onset anarthria without hepatic manifestation: a rare presentation of Wilson disease.

    PubMed

    Verma, Rajesh; Bhandari, Aveg; Tiwari, Navin; Chaudhari, Tejendra S

    2013-08-20

    Wilson disease (WD) is one of the few inherited but treatable disorder mainly affecting the liver and brain resulting in severe disability or death if left untreated. Hence, it is important to keep a high index of suspicion for diagnosing this clinical entity in appropriate clinical settings. The clinical presentation can be quite variable and they may present solely with neurological features sans hepatic symptoms. Such neurological manifestations usually follow subacute to chronic course. Acute onset anarthria as the heralding and predominant presenting feature has been rarely reported in the literature. We reported a case of a 12-year-old girl who presented with acute onset anarthria and dystonia of 1-month duration. On further evaluation, a diagnosis of WD was made. The patient showed partial improvement after she was started on copper chelating agents and anticholinergics.

  11. Acute onset anarthria without hepatic manifestation: a rare presentation of Wilson disease

    PubMed Central

    Verma, Rajesh; Bhandari, Aveg; Tiwari, Navin; Chaudhari, Tejendra S

    2013-01-01

    Wilson disease (WD) is one of the few inherited but treatable disorder mainly affecting the liver and brain resulting in severe disability or death if left untreated. Hence, it is important to keep a high index of suspicion for diagnosing this clinical entity in appropriate clinical settings. The clinical presentation can be quite variable and they may present solely with neurological features sans hepatic symptoms. Such neurological manifestations usually follow subacute to chronic course. Acute onset anarthria as the heralding and predominant presenting feature has been rarely reported in the literature. We reported a case of a 12-year-old girl who presented with acute onset anarthria and dystonia of 1-month duration. On further evaluation, a diagnosis of WD was made. The patient showed partial improvement after she was started on copper chelating agents and anticholinergics. PMID:23966348

  12. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: Different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation

    SciTech Connect

    Hanna, M.G.; Nelson, I.; Sweeney, M.G.; Cooper, J.M.; Watkins, P.J.; Morgan-Hughes, J.A.; Harding, A.E.

    1995-05-01

    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. 43 refs., 4 figs., 1 tab.

  13. Vapor, Dust and Smoke Exposure in relation to adult-onset asthma and chronic respiratory symptoms: The Singapore Chinese Health Study

    PubMed Central

    LeVan, Tricia D.; Koh, Woon-Puay; Lee, Hin-Peng; Koh, David; Yu, Mimi C.; London, Stephanie J.

    2006-01-01

    Occupational factors contribute to a significant fraction of respiratory disease and symptoms. We evaluated the role of occupational exposures on asthma, chronic bronchitis, and respiratory symptoms in a population-based cohort, the Singapore Chinese Health Study. History of occupations, occupational exposures, and respiratory conditions were collected by interviews with 52,325 Singaporeans born 1918–1953. Exposure to dusts, from cotton, wood, metal, mineral and/or asbestos, was associated with non-chronic cough and/or phlegm (OR = 1.19, 95% CI = 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% CI = 1.01, 1.57) and adult-onset asthma (OR = 1.14, 95% CI = 1.00, 1.30). Cotton dust was the major component contributing to respiratory symptoms. Vapor exposure, from chemical solvents, dyes, cooling oils, paints, wood preservatives and/or pesticides, was associated with non-chronic cough or phlegm (OR = 1.14, 95% CI = 1.03, 1.27), chronic dry cough (OR = 1.55, 95% CI = 1.19, 2.01) and adult-onset asthma (OR = 1.34, 95% CI = 1.15, 1.56). Chemical solvents, cooling oils and pesticides were the major sources contributing to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness. PMID:16707657

  14. A Corticobasal Syndrome Variant of Familial Creutzfeldt-Jakob Disease with Stroke-Like Onset

    PubMed Central

    2016-01-01

    Creutzfeldt-Jakob disease (CJD) is an untreatable rare human prion disease characterized by rapidly progressive dementia along with various neurological features, including myoclonus and sometimes other movement disorders. The clinical course is typically insidious and rapid, leading to an early death. In general, the most common form is sporadic CJD; however, Slovakia is typical for a high percentage of genetic cases. We present an unusual case report of a 65-year-old man with a sudden, stroke-like onset of motor aphasia with right-sided levodopa unresponsive parkinsonism, alien hand, and other characteristic features of corticobasal syndrome (CBS), with rapid deterioration and death on the 32nd day of the disease. Various neurodegenerative disorders are manifested with CBS as a clinical phenotype, including corticobasal degeneration (CBD), progressive supranuclear palsy, Alzheimer's disease, and CJD. In our patient, mutation E200K and M129M polymorphism of the PRNP gene and typical immunohistochemical findings pointed to a diagnosis of CJD. The patient's mother died of CJD many years ago. Several CBS-CJD cases were described, but the atypical stroke-like onset of CBS-CJD, an extremely rare presentation of CJD, makes our case unique worldwide. PMID:27803826

  15. Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1β Inhibition

    PubMed Central

    Goldbach-Mansky, Raphaela; Dailey, Natalie J.; Canna, Scott W.; Gelabert, Ana; Jones, Janet; Rubin, Benjamin I.; Kim, H. Jeffrey; Brewer, Carmen; Zalewski, Christopher; Wiggs, Edythe; Hill, Suvimol; Turner, Maria L.; Karp, Barbara I.; Aksentijevich, Ivona; Pucino, Frank; Penzak, Scott R.; Haverkamp, Margje H.; Stein, Leonard; Adams, Barbara S.; Moore, Terry L.; Fuhlbrigge, Robert C.; Shaham, Bracha; Jarvis, James N.; O’Neil, Kathleen; Vehe, Richard K.; Beitz, Laurie O.; Gardner, Gregory; Hannan, William P.; Warren, Robert W.; Horn, William; Cole, Joe L.; Paul, Scott M.; Hawkins, Philip N.; Pham, Tuyet Hang; Snyder, Christopher; Wesley, Robert A.; Hoffmann, Steven C.; Holland, Steven M.; Butman, John A.; Kastner, Daniel L.

    2014-01-01

    BACKGROUND Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation. METHODS We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1–receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare. RESULTS All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events. CONCLUSIONS Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations. (ClinicalTrials.gov number, NCT00069329.) PMID:16899778

  16. A Unified Hypothesis of Early- and Late-Onset Alzheimer's Disease Pathogenesis.

    PubMed

    Atwood, Craig S; Bowen, Richard L

    2015-01-01

    Early-onset familial Alzheimer's disease (EOFAD) and late-onset sporadic AD (LOSAD) both follow a similar pathological and biochemical course that includes: neuron and synapse loss and dysfunction, microvascular damage, microgliosis, extracellular amyloid-β deposition, tau phosphorylation, formation of intracellular neurofibrillary tangles, endoreduplication and related cell cycle events in affected brain regions. Any mechanistic explanation of AD must accommodate these biochemical and neuropathological features for both forms of the disease. In this insight paper we provide a unifying hypothesis for EOFAD and LOSAD that proposes that the aberrant re-entry of terminally differentiated, post-mitotic neurons into the cell division cycle is a common pathway that explains both early and late-onset forms of AD. Cell cycle abnormalities appear very early in the disease process, prior to the appearance of plaques and tangles, and explain the biochemical (e.g. tau phosphorylation), neuropathological (e.g. neuron hypertrophy; polypoidy) and cognitive changes observed in EOFAD and LOSAD. Genetic mutations in AβPP, PSEN1, and PSEN2 that alter amyloid-β precursor protein and Notch processing drive reactivation of the cell cycle in EOFAD, while age-related reproductive endocrine dyscrasia that upregulates mitogenic TNF signaling and AβPP processing toward the amyloidogenic pathway drives reactivation of the cell cycle in LOSAD. In essence, AβPP and presenilin mutations initiate early, what endocrine dyscrasia initiates later: aberrant cell cycle re-entry of post-mitotic neurons leading to neurodegeneration and cognitive decline in AD. Inhibition of cell cycle re-entry in post-mitotic neurons may be a useful therapeutic strategy to prevent, slow or halt disease progression.

  17. Microglial activation in regions related to cognitive function predicts disease onset in Huntington's disease: a multimodal imaging study.

    PubMed

    Politis, Marios; Pavese, Nicola; Tai, Yen F; Kiferle, Lorenzo; Mason, Sarah L; Brooks, David J; Tabrizi, Sarah J; Barker, Roger A; Piccini, Paola

    2011-02-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder associated with motor, cognitive and psychiatric deficits. This study, using a multimodal imaging approach, aims to assess in vivo the functional and structural integrity of regions and regional networks linked with motor, cognitive and psychiatric function. Predicting disease onset in at risk individuals is problematic and thus we sought to investigate this by computing the 5-year probability of HD onset (p5 HD) and relating it to imaging parameters. Using MRI, (11)C-PK11195 and (11)C-raclopride PET, we have investigated volumes, levels of microglial activation and D2/D3 receptor binding in CAG repeat-matched groups of premanifest and symptomatic HD gene carriers. Findings were correlated with disease-burden and UHDRS scores. Atrophy was detected in sensorimotor striatum (SMST), substantia nigra, orbitofrontal and anterior prefrontal cortex in the premanifest HD. D2/D3 receptor binding was reduced and microglial activation increased in SMST and associative striatum (AST), bed nucleus of the stria terminalis, the amygdala and the hypothalamus. In symptomatic HD cases this extended to involve atrophy in globus pallidus, limbic striatum, the red nuclei, anterior cingulate cortex, and insula. D2/D3 receptor binding was additionally reduced in substantia nigra, globus pallidus, limbic striatum, anterior cingulate cortex and insula, and microglial activation increased in globus pallidus, limbic striatum and anterior prefrontal cortex. In premanifest HD, increased levels of microglial activation in the AST and in the regional network associated with cognitive function correlated with p5 HD onset. These data suggest that pathologically activated microglia in AST and other areas related to cognitive function, maybe better predictors of clinical onset and stresses the importance of early cognitive assessment in HD.

  18. Atypical presentation of infantile-onset farber disease with novel ASAH1 mutations.

    PubMed

    Kim, Soo Yeon; Choi, Sun Ah; Lee, Sangmoon; Lee, Jin Sook; Hong, Che Ry; Lim, Byung Chan; Kang, Hyoung Jin; Kim, Ki Joong; Park, Sung-Hye; Choi, Murim; Chae, Jong-Hee

    2016-11-01

    Farber disease is a very rare autosomal recessive disease caused by mutation of ASAH1 that results in the accumulation of ceramide in various tissues. Clinical symptoms of classic Farber disease comprise painful joint deformity, hoarseness of voice, and subcutaneous nodules. Here, we describe a patient with Farber disease with atypical presentation of early onset hypotonia, sacral mass, congenital heart disease, and dysmorphic face since birth. Severe cognitive disability, failure to gain motor skills, failure to thrive, and joint contractures developed. Using whole-exome sequencing, we identified the compound heterozygote missense mutations of ASAH1 (p.R333C and p.G235R). Because of the diagnostic delay, she underwent sacral mass excision, which revealed enlarged lysosomes and zebra bodies. We report an atypical presentation of Farber disease with her pathology and associated genetic defect. This case expands the phenotypic spectrum of Farber disease to include novel mutations of ASAH1, which pose a diagnostic challenge. We also discuss the clinical utility of whole-exome sequencing for diagnosis of ultra-rare diseases. © 2016 Wiley Periodicals, Inc.

  19. Community-onset Klebsiella pneumoniae pneumonia in Taiwan: clinical features of the disease and associated microbiological characteristics of isolates from pneumonia and nasopharynx.

    PubMed

    Lin, Yi-Tsung; Wang, Yu-Ping; Wang, Fu-Der; Fung, Chang-Phone

    2015-01-01

    Klebsiella pneumoniae is an important cause of community-onset pneumonia in Asian countries and South Africa. We investigated the clinical characteristics of K. pneumoniae causing community-onset pneumonia, and the associated microbiological features between K. pneumoniae isolates from pneumonia and those from the nasopharynx in Taiwan. This study was conducted at the Taipei Veterans General Hospital during July, 2012 to February, 2014. The clinical characteristics in patients with community-onset K. pneumoniae pneumonia were analyzed. K. pneumoniae isolates from the nasopharynx of adults attending otorhinolaryngology outpatient clinics were collected to compare their microbiological features with those from pneumonia. Capsular genotypes, antimicrobial susceptibility, and multilocus sequence type (MLST) were determined among these strains. Ninety-one patients with community-onset K. pneumoniae pneumonia were enrolled. We found a high mortality (29.7%) among these patients. Capsular types K1, K2, K5, K20, K54, and K57 accounted for ∼70% of the K. pneumoniae isolates causing pneumonia, and ∼70% of all the K. pneumoniae strains isolated from the nasopharynx of patients in outpatient clinics. The MLST profiles further demonstrated the genetic relatedness between most pneumonia isolates and those from the nasopharynx. In conclusion, our results show that community-onset pneumonia caused by K. pneumoniae was associated with high mortality and could have a reservoir in the nasopharynx. To tackle this high-mortality disease, the distribution of capsular types in the nasopharynx might have implications for future vaccine development.

  20. Implications of Lifecourse Epidemiology for Research on Determinants of Adult Disease

    PubMed Central

    Liu, Sze; Jones, Richard N.; Glymour, M. Maria

    2013-01-01

    Many diseases commonly associated with aging are now thought to have social and physiologic antecedents in early life. Understanding how the timing of exposure to early life risk factors influences later-life health may illuminate mechanisms driving adult health inequalities and identify possible points for effective interventions. Recognizing chronic diseases as developing across the lifecourse also has implications for the conduct of research on adult risk factors for disease. We review alternative conceptual models that describe how the timing of risk factor exposure relates to the development of disease. We propose some expansions of lifecourse models to improve their relevance for research on adult chronic disease, using the relationship between education and adult cognitive decline and dementia as an example. We discuss the important implications each of the lifecourse conceptual models has on study design, analysis, and interpretation of research on aging and chronic diseases. We summarize several research considerations implied by the lifecourse framework, including: advantages of analyzing change in function rather than onset of impairment; the pervasive challenge of survivor bias; the importance of controlling for possible confounding by early life conditions; and the likely heterogeneity in responses of adults to treatment. PMID:24639598

  1. Evaluation of Adults With Congenital Heart Disease.

    PubMed

    Graziani, Francesca; Delogu, Angelica Bibiana

    2016-03-01

    The clinical approach to adults with congenital heart diseases (ACHDs) is unique in cardiovascular medicine because these patients encompass a broad range of presentations. Each patient, despite having similar diagnosis, will be anatomically and physiologically unlike others within ACHD population, in relation to the type of repair, age at repair, associated defects, with specific long-term risk factors and complications. Furthermore, as many patients will not complain of symptoms, clinical evaluation and diagnostic testing must also be based on the underlying main diagnostic category, with complete standardized lesion-specific clinical protocols, investigating all known risk factors specific for each congenital heart disease and performed as part of screening for significant long-term complications. The first part of this review will focus on clinical history, physical examination, and the most important diagnostic testing in ACHD population. The second part of the article will focus on some clinical issues we have to face in our daily practice, such as heart failure, cyanosis, and pulmonary hypertension. Furthermore, as survival rates of ACHD population continue to improve and patients with this condition live longer, we will briefly report on a new clinical concern regarding the impact of acquired morbidities like coronary artery disease that appear to be of greater importance in defining outcome in older patients with ACHD.

  2. Transgenic over-expression of mammalian heparanase delays prion disease onset and progression

    PubMed Central

    Kovalchuk Ben-Zaken, O; Nissan, I; Tzaban, S; Taraboulos, A; Zcharia, E; Matzger, S; Shafat, I; Vlodavsky, I; Tal, Y.

    2015-01-01

    Cellular heparan sulfate (HS) has a dual role in scrapie pathogenesis; it is required for PrPSc (scrapie prion protein) formation and facilitates infection of cells, mediating cellular uptake of prions. We examined the involvement of heparanase, a mammalian endoglycosidase degrading HS, in scrapie infection. In cultured cells, heparanase treatment or over-expression resulted in a profound decrease in PrPSc. Moreover, disease onset and progression were dramatically delayed in scrapie infected transgenic mice over-expressing heparanase. Together, our results provide direct in vivo evidence for the involvement of intact HS in the pathogenesis of prion disease and the protective role of heparanase both in terms of susceptibility to infection and disease progression. PMID:26168721

  3. GIGYF2 mutation in late-onset Parkinson's disease with cognitive impairment.

    PubMed

    Ruiz-Martinez, Javier; Krebs, Catharine E; Makarov, Vladimir; Gorostidi, Ana; Martí-Massó, Jose Félix; Paisán-Ruiz, Coro

    2015-10-01

    Although in the last two decades there has been considerable progress in understanding the genetic basis of Parkinson's disease (PD), the majority of PD is sporadic and its genetic causes are largely unknown. In an attempt to identify novel genetic causes of PD, whole-exome sequencing and subsequent analyses were performed in a family featuring late-onset PD with cognitive impairment. A novel genetic variant (p.Arg610Gly) in the GIGYF2 gene, previously known to be associated with PD, was identified as potential disease-causing mutation. The GIGYF2 p.Arg610Gly mutation situated in the GYF domain of the encoding protein was predicted to be pathogenic and to disrupt the GYF's ligand-binding abilities. Although further research is still required, this finding may shed light on the GIGYF2-associated mechanisms that lead to PD and suggests insulin dysregulation as a disease-specific mechanism for both PD and cognitive dysfunction.

  4. Early childhood poverty, immune-mediated disease processes, and adult productivity.

    PubMed

    Ziol-Guest, Kathleen M; Duncan, Greg J; Kalil, Ariel; Boyce, W Thomas

    2012-10-16

    This study seeks to understand whether poverty very early in life is associated with early-onset adult conditions related to immune-mediated chronic diseases. It also tests the role that these immune-mediated chronic diseases may play in accounting for the associations between early poverty and adult productivity. Data (n = 1,070) come from the US Panel Study of Income Dynamics and include economic conditions in utero and throughout childhood and adolescence coupled with adult (age 30-41 y) self-reports of health and economic productivity. Results show that low income, particularly in very early childhood (between the prenatal and second year of life), is associated with increases in early-adult hypertension, arthritis, and limitations on activities of daily living. Moreover, these relationships and particularly arthritis partially account for the associations between early childhood poverty and adult productivity as measured by adult work hours and earnings. The results suggest that the associations between early childhood poverty and these adult disease states may be immune-mediated.

  5. Evaluation of quality indicators and disease damage in childhood-onset systemic lupus erythematosus patients.

    PubMed

    Harris, Julia G; Maletta, Kristyn I; Kuhn, Evelyn M; Olson, Judyann C

    2017-02-01

    The aim of this study was to describe compliance with select quality indicators and assess organ-specific dysfunction in a childhood-onset systemic lupus erythematosus population by using a validated damage index and to evaluate associations between compliance with quality indicators and disease damage. A retrospective chart review was performed on patients diagnosed with systemic lupus erythematosus prior to age 18 followed at a single center in the USA from 1999 to 2012 (n = 75). Data regarding quality indicators and outcome variables, including the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, were collected. The median disease duration was 3.8 years. The proportion of patients or patient-years in which care complied with the proposed quality measures was 94.4% for hydroxychloroquine use, 84.3% for vitamin D recommendation,75.8% for influenza vaccination (patient-years), 67.2% for meningococcal vaccination, 49.0% for ophthalmologic examination (patient-years), 31.7% for pneumococcal vaccination, and 28.6% for bone mineral density evaluation. Disease damage was present in 41.3% of patients at last follow-up, with an average damage index score of 0.81. Disease damage at last follow-up was associated with minority race/ethnicity (p = 0.008), bone mineral density evaluation (p = 0.035), and vitamin D recommendation (p = 0.018). Adherence to quality indicators in a childhood-onset systemic lupus erythematosus population is varied, and disease damage is prevalent. This study highlights the importance of quality improvement initiatives aimed at optimizing care delivery to reduce disease damage in pediatric lupus patients.

  6. Comprehensive mutation screening for 10 genes in Chinese patients suffering very early onset inflammatory bowel disease

    PubMed Central

    Xiao, Yuan; Wang, Xin-Qiong; Yu, Yi; Guo, Yan; Xu, Xu; Gong, Ling; Zhou, Tong; Li, Xiao-Qin; Xu, Chun-Di

    2016-01-01

    AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease (VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients. METHODS: A total of 13 Chinese pediatric patients with VEO-IBD were diagnosed from May 2012 and August 2014. The relevant clinical characteristics of these patients were analyzed. Then DNA in the peripheral blood from patients was extracted. Next generation sequencing (NGS) based on an Illumina-Miseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10RA, IL-10RB, NOD2, FUT2, IL23R, GPR35, GPR65, TNFSF15, and ADAM30. The Sanger sequencing was used to verify the variations detected in NGS. RESULTS: Out of the 13 pediatric patients, ten were diagnosed with Crohn’s disease, and three diagnosed with ulcerative colitis. Mutations in IL-10RA and IL-10RB were detected in five patients. There were four patients who had single nucleotide polymorphisms associated with IBD. Two patients had IL-10RA and FUT2 polymorphisms, and two patients had IL-10RB and FUT2 polymorphisms. Gene variations were not found in the rest four patients. Children with mutations had lower percentile body weight (1.0% vs 27.5%, P = 0.002) and hemoglobin (87.4 g/L vs 108.5 g/L, P = 0.040) when compared with children without mutations. Although the age of onset was earlier, height was shorter, and the response to treatment was poorer in the mutation group, there was no significant difference in these factors between groups. CONCLUSION: IL-10RA and IL-10RB mutations are common in Chinese children with VEO-IBD. Patients with mutations have an earlier disease onset, lower body weight and hemoglobin, and poorer prognosis. PMID:27350736

  7. Multilingualism (but not always bilingualism) delays the onset of Alzheimer disease: evidence from a bilingual community.

    PubMed

    Chertkow, Howard; Whitehead, Victor; Phillips, Natalie; Wolfson, Christina; Atherton, Julie; Bergman, Howard

    2010-01-01

    A recent paper by Bialystok et al in Neuropsychologia (vol. 45, pgs. 459 to 464) suggested that early bilingualism produced a statistically significant 4.1-year delay in onset of memory loss symptoms in older individuals with Alzheimer disease, possibly reflecting an increase in the cognitive reserve of these individuals. That study focused on multilingual elderly patients of whom 90% were immigrants. Our memory clinic, in Montreal Canada, has the advantage of having a large set of individuals who are either multilingual immigrants to Canada, or who are nonimmigrants but raised in both official languages of Canada--French and English. We thus attempted to replicate the above findings using a larger cohort in a different setting. We examined age at diagnosis of Alzheimer disease and age at symptom onset for all unilingual versus multilingual participants, and then for those who were nonimmigrant English/French bilinguals. Overall, we found a small but significant protective effect of more than 2 languages spoken, but we found no significant benefit in bilinguals overall in relation to age at diagnosis or age at symptom onset. However, in the immigrant group, the results mirrored those of Bialystok et al with 2 or more languages delaying the diagnosis of Alzheimer disease by almost 5 years. A trend toward the same effect was also seen in nonimmigrants whose first language was French. In contrast, in nonimmigrants whose first language was English, no such effect was found. These results are discussed in relation to the earlier findings and the theory of cognitive reserve.

  8. Motor onset and diagnosis in Huntington disease using the diagnostic confidence level

    PubMed Central

    Liu, Dawei; Long, Jeffrey D.; Zhang, Ying; Raymond, Lynn A.; Marder, Karen; Rosser, Anne; McCusker, Elizabeth A.; Mills, James A.; Paulsen, Jane S.

    2015-01-01

    Background Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Methods Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine-adenine-guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington's Disease Rating Scale. Results HD progression from unimpaired to impaired motor function, as well as the progression from motor impairment to diagnosis, were associated with the linear effect of age and CAG repeat length. Specifically, for every 1-year increase in age, the risk of transition in diagnostic confidence level increased by 11% (95% CI: 7-15%) and for one repeat length increase in CAG, the risk of transition in diagnostic confidence level increased by 47% (95% CI: 27-69%). Conclusions Findings show that CAG repeat length and age increased the likelihood of the first onset of motor impairment as well as the age at diagnosis. Results suggest that more accurate estimates of HD onset age can be obtained by incorporating the current status of diagnostic confidence level into predictive models. PMID:26410751

  9. Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset Parkinson's Disease

    PubMed Central

    Pal, Gian D.; Hall, Deborah; Ouyang, Bichun; Phelps, Jessica; Alcalay, Roy; Pauciulo, Michael W.; Nichols, William C.; Clark, Lorraine; Mejia-Santana, Helen; Blasucci, Lucia; Goetz, Christopher G.; Comella, Cynthia; Colcher, Amy; Gan-Or, Ziv; Rouleau, Guy A.; Marder, Karen

    2016-01-01

    Objective In a cohort of patients with young-onset Parkinson's disease (PD), the authors assessed (1) the prevalence of genetic mutations in those who enrolled in deep brain stimulation (DBS) programs compared with those who did not enroll DBS programs and (2) specific genetic and clinical predictors of DBS enrollment. Methods Subjects were participants from 3 sites (Columbia University, Rush University, and the University of Pennsylvania) in the Consortium on Risk for Early Onset Parkinson's Disease (CORE-PD) who had an age at onset < 51 years. The analyses presented here focus on glucocerebrosidase (GBA), leucine-rich repeat kinase 2 (LRRK2), and parkin (PRKN) mutation carriers. Mutation carrier status, demographic data, and disease characteristics in individuals who did and did not enroll in DBS were analyzed. The association between mutation status and DBS placement was assessed in logistic regression models. Results Patients who had PD with either GBA, LRRK2, or PRKN mutations were more common in the DBS group (n = 99) compared with the non-DBS group (n = 684; 26.5% vs. 16.8%, respectively; P = 0.02). In a multivariate logistic regression model, GBA mutation status (odds ratio, 2.1; 95% confidence interval, 1.0–4.3; P = 0.05) was associated with DBS surgery enrollment. However, when dyskinesia was included in the multivariate logistic regression model, dyskinesia had a strong association with DBS placement (odds ratio, 3.8; 95% confidence interval, 1.9–7.3; P < 0.0001), whereas the association between GBA mutation status and DBS placement did not persist (P = 0.25). Conclusions DBS populations are enriched with genetic mutation carriers. The effect of genetic mutation carriers on DBS outcomes warrants further exploration. PMID:27709117

  10. Early Infant Feeding Practices May Influence the Onset of Symptomatic Celiac Disease

    PubMed Central

    Sharma, Shiv Dayal; Gupta, Rajkumar; Goyal, Alok; Sharma, Aakash

    2016-01-01

    Purpose To study whether breastfeeding and breastfeeding status during gluten introduction influences the age at diagnosis of celiac disease (CD). In addition to study, whether the timing of gluten introduction influences the age at diagnosis of CD. Methods It was a hospital based observational study. Total 198 patients diagnosed with CD as per modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition (2012) criteria, aged between 6 months to 6 years were included. Detail history taken with special emphasis on breastfeeding and age of gluten introduction. Standard statistical methods used to analyze the data. Results Mean±standard deviation age of onset and diagnosis of CD in breastfed cases was 2.81±1.42 years and 3.68 ±1.55 years respectively as compared to 1.84±1.36 years and 2.70±1.65 years respectively in not breastfed cases (p<0.05). Those who had continued breastfeeding during gluten introduction and of longer duration had significantly delayed onset of disease. The age at onset of CD was under one year in 40.42% of the cases, who had started gluten before 6 months of age compared to only 12.58% of those who had started gluten later (p<0.001). The proposed statistical model showed that two variables, i.e., breast feeding status during gluten introduction and age at gluten introduction positively influencing the age at diagnosis of CD. Conclusion Delayed gluten introduction to infant's diet along with continuing breastfeeding, delays symptomatic CD. However, it is not clear from our study that these infant feeding practices provide permanent protection against the disease or merely delays the symptoms. PMID:28090467

  11. A new assay for fast, reliable CRIM status determination in infantile-onset Pompe disease.

    PubMed

    Wang, Zhaohui; Okamoto, Patricia; Keutzer, Joan

    2014-02-01

    Pompe disease is caused by a deficiency of acid α-glucosidase (GAA; EC, 3.2.1.20), and the infantile-onset form is rapidly fatal if left untreated. However, recombinant human GAA (rhGAA) enzyme replacement therapy (ERT) extends survival for infantile Pompe patients. Although cross-reactive immunologic material (CRIM)-negative patients, who lack detectable endogenous GAA, mount an immune response to rhGAA that renders the therapy ineffective, timely induction of immune tolerance in these patients may improve clinical outcomes. Previously, CRIM status has been determined by Western blot analysis in cultured skin fibroblasts, a process that can take a few weeks. We present a blood-based CRIM assay that can yield results within 48 to 72 h. Results from this assay have been confirmed by GAA Western blot analysis in fibroblasts or by GAA sequencing in a small number of Pompe disease patients. Rapid classification of CRIM status will assist in identifying the most effective treatment course and minimizing treatment delays in patients with infantile-onset Pompe disease.

  12. Is the NACP/Synuclein gene involved in early-onset Alheimer`s disease?

    SciTech Connect

    Champion, D.; Clerget-Darpoux, F.; Frebourg, T.

    1994-09-01

    The major component of senile plaques (SP), the most specific histologic lesion of Alzheimer`s disease (AD) is the A4 peptide, derived from a large precursor protein (APP). Recently, a second major component of SP has been isolated. This 35 AA peptide was named non-A4 component amyloid (NAC) and its precursor - a 140 AA protein - was named NACP. Computer homology search has allowed us to establish that the NACP gene is homologous to the rat synuclein gene which is expressed in neurons. Since APP mutations have been shown to cause early-onset Alzheimer`s disease (EOAD) in several families, we investigated whether the NACP/synuclein gene was also involved in familial early-onset Alzheimer`s disease (FEOAD). RT-PCR and direct sequencing of the entire NACP open reading frame did not reveal any alteration of the NACP coding sequence in lymphocytes of 26 unrelated FEOAD patients. We showed that the NACP/synuclein gene was alternatively spliced and that the different transcripts potentially encoded for distinct proteins all containing the NAC peptide. Accumulation of NAC in SP might result from a dysregulation of NACP/synuclein expression.

  13. Mutant TDP-43 within motor neurons drives disease onset but not progression in amyotrophic lateral sclerosis.

    PubMed

    Ditsworth, Dara; Maldonado, Marcus; McAlonis-Downes, Melissa; Sun, Shuying; Seelman, Amanda; Drenner, Kevin; Arnold, Eveline; Ling, Shuo-Chien; Pizzo, Donald; Ravits, John; Cleveland, Don W; Da Cruz, Sandrine

    2017-03-29

    Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43(Q331K) mice develop age- and mutant-dependent motor deficits from degeneration and death of motor neurons. Cre-recombinase-mediated excision of the TDP-43(Q331K) gene from motor neurons is shown to delay onset of motor symptoms and appearance of TDP-43-mediated aberrant nuclear morphology, and abrogate subsequent death of motor neurons. However, reduction of mutant TDP-43 selectively in motor neurons did not prevent age-dependent degeneration of axons and neuromuscular junction loss, nor did it attenuate astrogliosis or microgliosis. Thus, disease mechanism is non-cell autonomous with mutant TDP-43 expressed in motor neurons determining disease onset but progression defined by mutant acting within other cell types.

  14. Developmental Programming of Adult Disease: Reprogramming by Melatonin?

    PubMed

    Tain, You-Lin; Huang, Li-Tung; Hsu, Chien-Ning

    2017-02-16

    Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the "developmental origins of health and disease" (DOHaD) or "developmental programming". The DOHaD concept offers the "reprogramming" strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs.

  15. MAPPING THE PROGRESSION OF ATROPHY IN EARLY AND LATE ONSET ALZHEIMER’S DISEASE

    PubMed Central

    Migliaccio, R; Agosta, F; Possin, KL; Canu, E; Filippi, M; Rabinovici, GD; Rosen, HJ; Miller, BL; Gorno-Tempini, ML

    2015-01-01

    The term early age-of-onset Alzheimer’s disease (EOAD) identifies patients who meet criteria for AD, but show onset of symptoms before the age of 65. We map progression of gray matter (GM) atrophy in EOAD patients compared to late onset AD (LOAD). T1-weighted MRI scans were obtained at diagnosis and one-year follow-up from 15 EOAD, 10 LOAD, and 38 age-matched controls. Voxel-based and tensor-based morphometry were used, respectively, to assess the baseline and progression of atrophy. At baseline, EOAD patients already showed a widespread atrophy in temporal, parietal, occipital and frontal cortices. After one year, EOAD had atrophy progression in medial temporal and medial parietal cortices. At baseline, LOAD patients showed atrophy in the medial temporal regions only, and, after one year, an extensive pattern of atrophy progression in the same neocortical cortices of EOAD. Although atrophy mainly involved different lateral neocortical or medial temporal hubs at baseline, it eventually progressed along the same brain default-network regions in both groups. The cortical region showing a significant progression in both groups was the medial precuneus/posterior cingulate. PMID:25737041

  16. Onset of hippocampus-dependent memory impairments in 5XFAD transgenic mouse model of Alzheimer's disease.

    PubMed

    Girard, Stéphane D; Jacquet, Marlyse; Baranger, Kévin; Migliorati, Martine; Escoffier, Guy; Bernard, Anne; Khrestchatisky, Michel; Féron, François; Rivera, Santiago; Roman, François S; Marchetti, Evelyne

    2014-07-01

    The 5XFAD mice are an early-onset transgenic model of Alzheimer's disease (AD) in which amyloid plaques are first observed between two and four months of age in the cortical layer five and in the subiculum of the hippocampal formation. Although cognitive alterations have been described in these mice, there are no studies that focused on the onset of hippocampus-dependent memory deficits, which are a hallmark of the prodromal stage of AD. To identify when the first learning and memory impairments appear, 5XFAD mice of two, four, and six months of age were compared with their respective wild-type littermates using the olfactory tubing maze, which is a very sensitive hippocampal-dependent task. Deficits in learning and memory started at four months with a substantial increase at six months of age while no olfactory impairments were observed. The volumetric study using magnetic resonance imaging of the whole brain and specific areas (olfactory bulb, striatum, and hippocampus) did not reveal neuro-anatomical difference. Slight memory deficits appeared at 4 months of age in correlation with an increased astrogliosis and amyloid plaque formation. This early impairment in learning and memory related to the hippocampal dysfunction is particularly suited to assess preclinical therapeutic strategies aiming to delay or suppress the onset of AD.

  17. Iowa Gambling Task in patients with early-onset Parkinson's disease: strategy analysis.

    PubMed

    Gescheidt, Tomáš; Czekóová, Kristína; Urbánek, Tomáš; Mareček, Radek; Mikl, Michal; Kubíková, Radka; Telecká, Sabina; Andrlová, Hana; Husárová, Ivica; Bareš, Martin

    2012-12-01

    The aim of our study was to analyse decision making in early-onset Parkinson's disease (PD) patients performing the Iowa Gambling Task (IGT). We compared 19 patients with early-onset PD (≤ 45 years) on dopaminergic medication (no evidence of depression, dementia, executive dysfunction according to the Tower of London test and the Stroop test, or pathological gambling) with 20 age-matched controls. A computer version of the IGT was employed. The PD patients achieved slightly lower IGT scores than the control group. A detailed analysis based on 'shift frequencies' between the individual decks showed that the patients tended to change their preferences for the decks more frequently, with a higher preference for the 'disadvantageous' deck B. Control subjects seemed to develop a more effective strategy. These differences could be caused by the poorer ability of the patients to develop any strategy at all. We observed changes in decision making during IGT performance in patients with early-onset PD, although they had no executive dysfunction as measured by established neuropsychological tests. The more detailed analysis employed in the present study could lead to a more accurate study of IGT performance and application of IGT in clinical practice.

  18. Validation of DSM-5 age-of-onset criterion of attention deficit/hyperactivity disorder (ADHD) in adults: Comparison of life quality, functional impairment, and family function.

    PubMed

    Lin, Yu-Ju; Lo, Kuan-Wu; Yang, Li-Kuang; Gau, Susan Shur-Fen

    2015-12-01

    The newly published Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) elevates the threshold of the ADHD age-of-onset criterion from 7 to 12 years. This study evaluated the quality of life and functional impairment of adults with ADHD who had symptoms onset by or after 7 years and examined the mediation effect of family function and anxiety/depression symptoms between ADHD diagnosis and quality of life and functional impairment. We assessed 189 adults with ADHD and 153 non-ADHD controls by psychiatric interview and self-administered reports on the Adult ADHD Quality of Life Scale, Weiss Functional Impairment Rating Scale, Family APGAR, and Adult Self Report Inventory-4. The ADHD group was divided into early-onset ADHD (onset <7 years, n=147) and late-onset ADHD (onset between 7 and 12 years, n=42). The mediation analysis was conducted to verify the mediating factors from ADHD to functional impairment and quality of life. The late-onset ADHD had more severe functional impairment at work and poorer family support than early-onset ADHD while they had comparable impairment at other domains. Less perceived family support and current anxiety/depressive symptoms partially mediated the link between ADHD diagnosis and quality of life/functional impairment both in early- and late-onset ADHD. Our data support decreased quality of life and increased functional impairment in adult ADHD, regardless of age of onset, and these adverse outcomes may be mediated by family support and anxiety/depression at adulthood. Our findings also imply that the new DSM-5 ADHD criteria do not over-include individuals without impairment.

  19. Mechanism of interrupted saccades in patients with late-onset Tay-Sachs disease.

    PubMed

    Optican, Lance M; Rucker, Janet C; Keller, Edward L; Leigh, R John

    2008-01-01

    In late-onset Tay-Sachs disease (LOTS), saccades are interrupted by one or more transient decelerations. Some saccades reaccelerate and continue on before eye velocity reaches zero, even in darkness. Intervals between successive decelerations are not regularly spaced. Peak decelerations of horizontal and vertical components of oblique saccades in LOTS is more synchronous than those in control subjects. We hypothesize that these decelerations are caused by dysregulation of the fastigial nuclei (FN) of the cerebellum, which fire brain stem inhibitory burst neurons (IBNs).

  20. Computed tomography phenotypes in severe, early-onset chronic obstructive pulmonary disease.

    PubMed

    Hersh, Craig P; Jacobson, Francine L; Gill, Ritu; Silverman, Edwin K

    2007-12-01

    Subjects with severe chronic obstructive pulmonary disease (COPD) may have marked differences in emphysema severity on chest computed tomography (CT) scans. Although many patients with severe COPD will have chest CTs performed during their clinical care, chest CTs have not been widely included in epidemiologic and genetic studies of COPD. We sought to determine whether chest CT scans performed for clinical indications can provide useful data in an epidemiologic study of COPD and to determine whether chest CT scans can be used to define subtypes of severe, early-onset COPD. Clinical chest CT scans on 91 probands in the Boston Early-Onset COPD Study were retrospectively reviewed by 2 pulmonologists and 1 to 2 chest radiologists, using a semi-quantitative emphysema severity score, ranging from 0-24. 88 of 91 chest CT scans were suitable for emphysema analysis. There was a wide range of emphysema severity, from mild to severe (1.3-23.7). Emphysema-predominant subjects (upper 3 quartiles of emphysema scores) had more severe airflow obstruction than airway-predominant subjects (lowest quartile of emphysema scores): FEV(1) 17.4% vs. 22.4% predicted, p=0.009. A higher percentage of airway-predominant subjects had a positive bronchodilator response (28.6% vs. 6.7%, p=0.009). Airway-predominant subjects also had a higher frequency of physician-diagnosed asthma (p=0.04) and a trend towards higher serum immunoglobulin E levels (p=0.09). Analysis of siblings of early-onset COPD probands suggested a genetic contribution to the subgroups. Using clinical chest CT scans, we were able to identify an airway-predominant subgroup with asthma-like features among subjects with severe, early-onset COPD.

  1. Executive Abilities as Reflected by Clock Hand Placement: Frontotemporal Dementia Versus Early-Onset Alzheimer Disease.

    PubMed

    Barrows, Robin J; Barsuglia, Joseph; Paholpak, Pongsatorn; Eknoyan, Donald; Sabodash, Valeriy; Lee, Grace J; Mendez, Mario F

    2015-12-01

    The clock-drawing test (CDT) is widely used in clinical practice to diagnose and distinguish patients with dementia. It remains unclear, however, whether the CDT can distinguish among the early-onset dementias. Accordingly, we examined the ability of both quantitative and qualitative CDT analyses to distinguish behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer disease (eAD), the 2 most common neurodegenerative dementias with onset <65 years of age. We hypothesized that executive aspects of the CDT would discriminate between these 2 disorders. The study compared 15 patients with bvFTD and 16 patients with eAD on the CDT using 2 different scales and correlated the findings with neuropsychological testing and magnetic resonance imaging. The total CDT scores did not discriminate bvFTD and eAD; however, specific analysis of executive hand placement items successfully distinguished the groups, with eAD exhibiting greater errors than bvFTD. The performance on those executive hand placement items correlated with measures of naming as well as visuospatial and executive function. On tensor-based morphometry of the magnetic resonance images, executive hand placement correlated with right frontal volume. These findings suggest that lower performance on executive hand placement items occurs with involvement of the right dorsolateral frontal-parietal network for executive control in eAD, a network disproportionately affected in AD of early onset. Rather than the total performance on the clock task, the analysis of specific errors, such as executive hand placement, may be useful for early differentiation of eAD, bvFTD, and other conditions.

  2. Protective Connections and Educational Attainment among Young Adults with Childhood-Onset Chronic Illness

    ERIC Educational Resources Information Center

    Maslow, Gary; Haydon, Abigail A.; McRee, Annie-Laurie; Halpern, Carolyn T.

    2012-01-01

    Background: Youth with childhood-onset chronic illness (COCI) are at risk of poor educational attainment. Specific protective factors that promote college graduation in this population have not been studied previously. In this study, we examine the role protective factors during adolescence play in promoting college graduation among young adults…

  3. The History and Timing of Depression Onset as Predictors of Young Adult Self-Esteem

    ERIC Educational Resources Information Center

    Gayman, Mathew D.; Lloyd, Donald A.; Ueno, Koji

    2011-01-01

    Depression often emerges early in the lifecourse and is consistently shown to be associated with poor self-esteem. The 3 main objectives of the current study are to (1) evaluate the association between a history major depression and self-esteem in young adulthood, (2) assess the relationship between timing of depression onset and young adult…

  4. Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.

    PubMed

    Koeberl, Dwight D; Austin, Stephanie; Case, Laura E; Smith, Edward C; Buckley, Anne F; Young, Sarah P; Bali, Deeksha; Kishnani, Priya S

    2014-05-01

    Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.

  5. A systematic screening to identify de novo mutations causing sporadic early-onset Parkinson's disease

    PubMed Central

    Kun-Rodrigues, Celia; Ganos, Christos; Guerreiro, Rita; Schneider, Susanne A.; Schulte, Claudia; Lesage, Suzanne; Darwent, Lee; Holmans, Peter; Singleton, Andrew; Bhatia, Kailash; Bras, Jose

    2015-01-01

    Despite the many advances in our understanding of the genetic basis of Mendelian forms of Parkinson's disease (PD), a large number of early-onset cases still remain to be explained. Many of these cases, present with a form of disease that is identical to that underlined by genetic causes, but do not have mutations in any of the currently known disease-causing genes. Here, we hypothesized that de novo mutations may account for a proportion of these early-onset, sporadic cases. We performed exome sequencing in full parent–child trios where the proband presents with typical PD to unequivocally identify de novo mutations. This approach allows us to test all genes in the genome in an unbiased manner. We have identified and confirmed 20 coding de novo mutations in 21 trios. We have used publicly available population genetic data to compare variant frequencies and our independent in-house dataset of exome sequencing in PD (with over 1200 cases) to identify additional variants in the same genes. Of the genes identified to carry de novo mutations, PTEN, VAPB and ASNA1 are supported by various sources of data to be involved in PD. We show that these genes are reported to be within a protein–protein interaction network with PD genes and that they contain additional rare, case-specific, mutations in our independent cohort of PD cases. Our results support the involvement of these three genes in PD and suggest that testing for de novo mutations in sporadic disease may aid in the identification of novel disease-causing genes. PMID:26362251

  6. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer's disease.

    PubMed

    An, Seong Soo; Park, Sun Ah; Bagyinszky, Eva; Bae, Sun Oh; Kim, Yoon-Jeong; Im, Ji Young; Park, Kyung Won; Park, Kee Hyung; Kim, Eun-Joo; Jeong, Jee Hyang; Kim, Jong Hun; Han, Hyun Jeong; Choi, Seong Hye; Kim, SangYun

    2016-01-01

    Early-onset Alzheimer's disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer's disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer's disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16-17), PSEN1 (exons 3-12), and PSEN2 (exons 3-12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We

  7. A review of the economics of adult congenital heart disease.

    PubMed

    Seckeler, Michael D; Thomas, Ian D; Andrews, Jennifer; Joiner, Keith; Klewer, Scott E

    2016-01-01

    Adults living with congenital heart disease (CHD) now outnumber children with the disease. Thanks to medical advances over the past 75 years, many of these fatal childhood heart problems have changed to chronic medical conditions. As the population of adults with CHD increases, they will require increasingly complex medical, surgical and catheter-based therapies. In addition, social burdens including education, employment and insurability, which increase the societal costs of adult CHD, are now being recognized for adults living with CHD. This review summarizes the available literature on the economics of adult CHD.

  8. Late-onset acute graft-versus-host disease mimicking hand, foot, and mouth disease

    PubMed Central

    Mahabal, Gauri; George, Leni; Bindra, Mandeep; George, Biju

    2016-01-01

    Acute skin graft-versus-host disease (GVHD) classically presents as a pruritic erythematous maculopapular rash. We describe a patient who underwent allogeneic hematopoietic stem cell transplantation and presented with a hand foot and mouth disease like clinical presentation. Histopathology was suggestive of acute GVHD. This case is being reported to make dermatologists aware of this unusual presentation of GVHD. PMID:27990387

  9. The nature of excessive sleepiness and sudden sleep onset in Parkinson׳s disease

    PubMed Central

    Távora, Daniel Gurgel Fernandes; de Bruin, Veralice Meireles Sales; Lopes Gama, Romulo; Lopes, Emily Mourão Soares; Jorge, Iago Farias; de Bruin, Pedro Felipe Carvalhedo

    2014-01-01

    Objectives Excessive daytime sleepiness (EDS) and sudden sleep onset (SOS) episodes are frequent in Parkinson׳s disease (PD). The objectives are to identify clinical characteristics and factors associated with EDS and SOS episodes. Methods Clinical demographic data were recorded (N=100, mean age=65.0±10.4). EDS was identified by the Epworth Sleepiness Scale (ESS>10) and SOS episodes were registered. Disease severity was evaluated by the Unified Parkinson׳s Disease Rating Scale (UPDRS, I, II, and III), sleep disturbances by the Parkinson׳s Disease Sleep Scale (PDSS<100), depressive symptoms by the Beck Depression Inventory (BDI>10) and rapid eye movement (REM) sleep behavior disorder (RBD) by the REM sleep behavior scale. Levodopa equivalent dose was measured. Results: PD patients with EDS (67%) were predominately male (73.1%) and had worse disease severity (UPDRS II and III p= 0.005); SOS episodes (39%) were associated with disease duration, diabetes, sleep disturbances (PDSS Scale), disease severity (UPDRS I, II, III) and RBD symptoms (p<0.05). Stepwise regression analysis showed that EDS was independently associated with motor-symptoms severity (UPDRS III scale, p=0.003). SOS episodes were independently associated with disease duration (p=0.006) and sleep disturbances (PDSS scale, p=0.03): patients had more uncomfortable immobility at night, tremor on waking and snoring or difficult breathing. Discussion EDS and or SOS episodes are frequent and manifest a differential pattern in PD. SOS episodes are associated with longer disease duration, diabetes, sleep disturbances and RBD symptoms indicating that these “sleep attacks” are of multifactorial origin and probably influenced by brain structural abnormalities. PMID:26483896

  10. Differences in Gene-Gene Interactions in Graves’ Disease Patients Stratified by Age of Onset

    PubMed Central

    Jurecka-Lubieniecka, Beata; Bednarczuk, Tomasz; Ploski, Rafal; Krajewska, Jolanta; Kula, Dorota; Kowalska, Malgorzata; Tukiendorf, Andrzej; Kolosza, Zofia; Jarzab, Barbara

    2016-01-01

    Background Graves’ disease (GD) is a complex disease in which genetic predisposition is modified by environmental factors. Each gene exerts limited effects on the development of autoimmune disease (OR = 1.2–1.5). An epidemiological study revealed that nearly 70% of the risk of developing inherited autoimmunological thyroid diseases (AITD) is the result of gene interactions. In the present study, we analyzed the effects of the interactions of multiple loci on the genetic predisposition to GD. The aim of our analyses was to identify pairs of genes that exhibit a multiplicative interaction effect. Material and Methods A total of 709 patients with GD were included in the study. The patients were stratified into more homogeneous groups depending on the age at time of GD onset: younger patients less than 30 years of age and older patients greater than 30 years of age. Association analyses were performed for genes that influence the development of GD: HLADRB1, PTPN22, CTLA4 and TSHR. The interactions among polymorphisms were analyzed using the multiple logistic regression and multifactor dimensionality reduction (MDR) methods. Results GD patients stratified by the age of onset differed in the allele frequencies of the HLADRB1*03 and 1858T polymorphisms of the PTPN22 gene (OR = 1.7, p = 0.003; OR = 1.49, p = 0.01, respectively). We evaluated the genetic interactions of four SNPs in a pairwise fashion with regard to disease risk. The coexistence of HLADRB1 with CTLA4 or HLADRB1 with PTPN22 exhibited interactions on more than additive levels (OR = 3.64, p = 0.002; OR = 4.20, p < 0.001, respectively). These results suggest that interactions between these pairs of genes contribute to the development of GD. MDR analysis confirmed these interactions. Conclusion In contrast to a single gene effect, we observed that interactions between the HLADRB1/PTPN22 and HLADRB1/CTLA4 genes more closely predicted the risk of GD onset in young patients. PMID:26943356

  11. Early Onset of Metastatic Gestational Trophoblastic Disease after Full-Term Pregnancy

    PubMed Central

    Ghaemmaghami, Fatemeh; Zarchi, Mojgan Karimi

    2008-01-01

    Choriocarcinoma is a curable malignancy that occurred approximately 50% after term pregnancies, and prognosis in this form of gestational trophoblastic Disease (GTD) is Poor. The earliest onset choriocarcinoma after term pregnancy in one study was reported 3 weeks after delivery, but in current study, choriocarcinoma was diagnosed 2 weeks after delivery. 28 years-old women gravidity 2, parity 2 delivered a healthy infant at term. Frequent episodes of vaginal bleeding occurred after 10 days of delivery. On admission to hospital, she had lesions in the lungs. The pretreatment human chorionic gonadotropin (HCG) level was 84,000 mIU/ml and her FIGO risk factor score was 8 (high risk group). The EMA/CO regimen was administered as first line chemotherapy and the patient achieved complete remission after 7 courses. Although early onset postpartum hemorrhage is due to complication of delivery, but gestational trophoblastic disease (GTD) may be occurred and assessment of human chorionic gonadotropin could be help to early diagnose of GTD. PMID:23675070

  12. SORL1 mutations in early- and late-onset Alzheimer disease

    PubMed Central

    Cuccaro, Michael L.; Carney, Regina M.; Zhang, Yalun; Bohm, Christopher; Kunkle, Brian W.; Vardarajan, Badri N.; Whitehead, Patrice L.; Cukier, Holly N.; Mayeux, Richard; St. George-Hyslop, Peter

    2016-01-01

    Objective: To characterize the clinical and molecular effect of mutations in the sortilin-related receptor (SORL1) gene. Methods: We performed whole-exome sequencing in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer disease (LOAD) families followed by functional studies of select variants. The phenotypic consequences associated with SORL1 mutations were characterized based on clinical reviews of medical records. Functional studies were completed to evaluate β-amyloid (Aβ) production and amyloid precursor protein (APP) trafficking associated with SORL1 mutations. Results: SORL1 alterations were present in 2 EOAD families. In one, a SORL1 T588I change was identified in 4 individuals with AD, 2 of whom had parkinsonian features. In the second, an SORL1 T2134 alteration was found in 3 of 4 AD cases, one of whom had postmortem Lewy bodies. Among LOAD cases, 4 individuals with either SORL1 A528T or T947M alterations had parkinsonian features. Functionally, the variants weaken the interaction of the SORL1 protein with full-length APP, altering levels of Aβ and interfering with APP trafficking. Conclusions: The findings from this study support an important role for SORL1 mutations in AD pathogenesis by way of altering Aβ levels and interfering with APP trafficking. In addition, the presence of parkinsonian features among select individuals with AD and SORL1 mutations merits further investigation. PMID:27822510

  13. Structured Regions of Alpha-synuclein Fibrils Include the Early Onset Parkinson's Disease Mutation Sites

    SciTech Connect

    Comellas Canal, Gemma; Lemkau, Luisel R.; Nieuwkoop, Andrew J.; Kloepper, Kathryn D.; Ladror, Daniel T.; Ebisu, Reika; Woods, Wendy S.; Lipton, Andrew S.; George, Julia M.; Rienstra, Chad M.

    2011-08-26

    Alpha-Synuclein (AS) fibrils constitute the major proteinaceous component of Lewy bodies (LBs), the pathological hallmark of Parkinson’s disease (PD) and other neurodegenerative diseases. Three single point mutations in the AS gene, as well as multiplication of the wild-type (WT) AS allele, have been previously identified in families with early-onset PD. Although AS fibrils have been the subject of intense study, critical details about their structure including the precise location of the B-strands and the extent of the core, the three-dimensional structure and the effects of the mutations—remain unknown. Here, we have used magic-angle spinning solid-state NMR spectroscopy to present a detailed characterization of the full-length WT AS fibrils. With improved sample preparations, isotopic labeling patterns and NMR experiments, we have confidently assigned more than 90% of the 13C and 15N backbone and sidechain chemical shifts of the detected residues from residue 39 to 97, and quantified the conformational dynamics throughout this region. Our results demonstrate that the core of AS fibrils extends with a repeated motif and that residues 30, 46 and 53-the early-onset PD mutant sites-are located in structured regions of AS fibrils.

  14. MTHFR Gene Mutations: A Potential Marker of Late-Onset Alzheimer's Disease?

    PubMed

    Román, Gustavo C

    2015-01-01

    Recent epigenome-wide association studies have confirmed the importance of epigenetic effects mediated by DNA methylation in late-onset Alzheimer's disease (LOAD). Metabolic folate pathways and methyl donor reactions facilitated by B-group vitamins may be critical in the pathogenesis of LOAD. Methylenetetrahydrofolate reductase (MTHFR) gene mutations were studied in consecutive Alzheimer's Disease & Memory Clinic patients up to December 2014. DNA analyses of MTHFR-C667T and - A1298C homozygous and heterozygous polymorphisms in 93 consecutive elderly patients revealed high prevalence of MTHFR mutations (92.5%). Findings require confirmation in a larger series, but MTHFR mutations may become a LOAD marker, opening novel possibilities for prevention and treatment.

  15. Clinical, genetic, and neuroimaging features of Early Onset Alzheimer Disease: the challenges of diagnosis and treatment.

    PubMed

    Alberici, Antonella; Benussi, Alberto; Premi, Enrico; Borroni, Barbara; Padovani, Alessandro

    2014-01-01

    Early Onset Alzheimer Disease (EOAD) is a rare condition, frequently associated with genetic causes. The dissemination of genetic testing along with biomarker determinations have prompted a wider recognition of EOAD in experienced clinical settings. However, despite the great efforts in establishing the contribution of causative genes to EOAD, atypical disease presentation and clinical features still makes its diagnosis and treatment a challenge for the clinicians. This review aims to provide an extensive evaluation of literature data on EOAD, in order to improve understanding and knowledge of EOAD, underscore its significant impact on patients and their caregivers and influence public policies. This would be crucial to define the urgency of evidence-based treatment approaches.

  16. QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease.

    PubMed

    Guarani, Virginia; Jardel, Claude; Chrétien, Dominique; Lombès, Anne; Bénit, Paule; Labasse, Clémence; Lacène, Emmanuelle; Bourillon, Agnès; Imbard, Apolline; Benoist, Jean-François; Dorboz, Imen; Gilleron, Mylène; Goetzman, Eric S; Gaignard, Pauline; Slama, Abdelhamid; Elmaleh-Bergès, Monique; Romero, Norma B; Rustin, Pierre; Ogier de Baulny, Hélène; Paulo, Joao A; Harper, J Wade; Schiff, Manuel

    2016-09-13

    Previously, we identified QIL1 as a subunit of mitochondrial contact site (MICOS) complex and demonstrated a role for QIL1 in MICOS assembly, mitochondrial respiration, and cristae formation critical for mitochondrial architecture (Guarani et al., 2015). Here, we identify QIL1 null alleles in two siblings displaying multiple clinical symptoms of early-onset fatal mitochondrial encephalopathy with liver disease, including defects in respiratory chain function in patient muscle. QIL1 absence in patients' fibroblasts was associated with MICOS disassembly, abnormal cristae, mild cytochrome c oxidase defect, and sensitivity to glucose withdrawal. QIL1 expression rescued cristae defects, and promoted re-accumulation of MICOS subunits to facilitate MICOS assembly. MICOS assembly and cristae morphology were not efficiently rescued by over-expression of other MICOS subunits in patient fibroblasts. Taken together, these data provide the first evidence of altered MICOS assembly linked with a human mitochondrial disease and confirm a central role for QIL1 in stable MICOS complex formation.

  17. Developmental Programming of Adult Disease: Reprogramming by Melatonin?

    PubMed Central

    Tain, You-Lin; Huang, Li-Tung; Hsu, Chien-Ning

    2017-01-01

    Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the “developmental origins of health and disease” (DOHaD) or “developmental programming”. The DOHaD concept offers the “reprogramming” strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs. PMID:28212315

  18. Juvenile idiopathic arthritis in adulthood: fulfilment of classification criteria for adult rheumatic diseases, long-term outcomes and predictors of inactive disease, functional status and damage

    PubMed Central

    Oliveira-Ramos, Filipa; Eusébio, Mónica; M Martins, Fernando; Mourão, Ana Filipa; Furtado, Carolina; Campanilho-Marques, Raquel; Cordeiro, Inês; Ferreira, Joana; Cerqueira, Marcos; Figueira, Ricardo; Brito, Iva; Santos, Maria José; Melo-Gomes, José A; Fonseca, João Eurico

    2016-01-01

    Objectives To determine how adult juvenile idiopathic arthritis (JIA) patients fulfil classification criteria for adult rheumatic diseases, evaluate their outcomes and determine clinical predictors of inactive disease, functional status and damage. Methods Patients with JIA registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) older than 18 years and with more than 5 years of disease duration were included. Data regarding sociodemographic features, fulfilment of adult classification criteria, Health Assessment Questionnaire, Juvenile Arthritis Damage Index—articular (JADI-A) and Juvenile Arthritis Damage Index—extra-articular (JADI-E) damage index and disease activity were analysed. Results 426 patients were included. Most of patients with systemic JIA fulfilled criteria for Adult Still's disease. 95.6% of the patients with rheumatoid factor (RF)-positive polyarthritis and 57.1% of the patients with RF-negative polyarthritis matched criteria for rheumatoid arthritis (RA). 38.9% of the patients with extended oligoarthritis were classified as RA while 34.8% of the patients with persistent oligoarthritis were classified as spondyloarthritis. Patients with enthesitis-related arthritis fulfilled criteria for spondyloarthritis in 94.7%. Patients with psoriatic arthritis maintained this classification. Patients with inactive disease had lower disease duration, lower diagnosis delay and corticosteroids exposure. Longer disease duration was associated with higher HAQ, JADI-A and JADI-E. Higher JADI-A was also associated with biological treatment and retirement due to JIA disability and higher JADI-E with corticosteroids exposure. Younger age at disease onset was predictive of higher HAQ, JADI-A and JADI-E and decreased the chance of inactive disease. Conclusions Most of the included patients fulfilled classification criteria for adult rheumatic diseases, maintain active disease and have functional impairment. Younger age at disease onset was predictive

  19. Isolated splenic cat scratch disease in an immunocompetent adult woman.

    PubMed

    Gilad, Jacob; Wolak, Arik; Borer, Abraham; Benharroch, Daniel; Avidor, Boaz; Giladi, Michael; Schlaeffer, Francisc

    2003-01-01

    We report a case of isolated splenic cat scratch disease in an immunocompetent woman. The clinical presentation of prolonged fever, night sweats, weakness, and intrasplenic lesions was highly suggestive of lymphoma. This is the second reported case of isolated splenic cat scratch disease in an adult and the first in a healthy adult.

  20. Facts about Meningococcal Disease for Adults

    MedlinePlus

    ... will have serious permanent disabilities like brain damage, hearing loss, and limb amputations. FACT: While some adults are at increased risk and need vaccination, adolescents and young adults generally have a higher risk ...

  1. Timing of onset of evening activity of adult chinese rose beetles (Coleoptera: Scarabaeidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult Chinese rose beetles, Adoretus sinicus (Burmeister) (Coleoptera: Scarabaeidae: Adoretini), present in China, Taiwan, Indonesia, Cambodia, Laos, Singapore, Thailand, Vietnam, the Marianas Islands, the Caroline Islands, and the Hawaiian Islands, are nighttime defoliators that feed on a wide vari...

  2. A Rare Case of Adult Onset Intussusception Complicated By Narcotic Dependence

    PubMed Central

    Khan, Saira J; Desmarais, Ashley M; Joseph, Bellal

    2017-01-01

    This report describes a rare case of adult intussusception in a patient with a history of a Roux-en-Y gastric bypass procedure; complicated by a history of narcotic abuse, methadone dependence, and methamphetamine abuse. Adult patients who have undergone a Roux-en-Y gastric bypass procedure may be at an increased risk of developing intussusception, and clinicians involved in their care should be aware of this potential complication. PMID:28191368

  3. Inframammary Dermatitis: A Case of Localized Late-Onset Darier's Disease

    PubMed Central

    Linder, Dennis; Marinello, Elena; Donisi, Pietro Maria; Salmaso, Roberto; Zattra, Edoardo; Zampetti, Anna

    2016-01-01

    Darier's disease (DD) is an autosomal dominant inherited genodermatosis which is often under- or misdiagnosed. In the majority of cases, the disease manifests in adolescents or young adults with small brownish-yellow, warty, hyperkeratotic papules in multiple seborrheic areas of the body. Localized DD (LDD) is a clinical variant, first described by Kreibich in 1906; only a few cases are reported in the literature. We described the case of an aged woman presenting with LDD, and we review the literature on this subject. PMID:27504089

  4. GC-MS metabolomic analysis reveals significant alterations in cerebellar metabolic physiology in a mouse model of adult onset hypothyroidism.

    PubMed

    Constantinou, Caterina; Chrysanthopoulos, Panagiotis K; Margarity, Marigoula; Klapa, Maria I

    2011-02-04

    Although adult-onset hypothyroidism (AOH) has been connected to neural activity alterations, including movement, behavioral, and mental dysfunctions, the underlying changes in brain metabolic physiology have not been investigated in a systemic and systematic way. The current knowledge remains fragmented, referring to different experimental setups and recovered from various brain regions. In this study, we developed and applied a gas chromatography-mass spectrometry (GC-MS) metabolomics protocol to obtain a holistic view of the cerebellar metabolic physiology in a Balb/cJ mouse model of prolonged adult-onset hypothyroidism induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. The high-throughput analysis enabled the correlation between multiple parallel-occurring metabolic phenomena; some have been previously related to AOH, while others implicated new pathways, designating new directions for further research. Specifically, an overall decline in the metabolic activity of the hypothyroid compared to the euthyroid cerebellum was observed, characteristically manifested in energy metabolism, glutamate/glutamine metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis. These alterations provide strong evidence that the mammalian cerebellum is metabolically responsive to AOH. In light of the cerebellum core functions and its increasingly recognized role in neurocognition, these findings further support the known phenotypic manifestations of AOH into movement and cog