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Sample records for g6pd deficiency assessment

  1. Assessment of Point-of-Care Diagnostics for G6PD Deficiency in Malaria Endemic Rural Eastern Indonesia

    PubMed Central

    Satyagraha, Ari W.; Sadhewa, Arkasha; Elvira, Rosalie; Elyazar, Iqbal; Feriandika, Denny; Antonjaya, Ungke; Oyong, Damian; Subekti, Decy; Rozi, Ismail E.; Domingo, Gonzalo J.; Harahap, Alida R.; Baird, J. Kevin

    2016-01-01

    Background Patients infected by Plasmodium vivax or Plasmodium ovale suffer repeated clinical attacks without primaquine therapy against latent stages in liver. Primaquine causes seriously threatening acute hemolytic anemia in patients having inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency. Access to safe primaquine therapy hinges upon the ability to confirm G6PD normal status. CareStart G6PD, a qualitative G6PD rapid diagnostic test (G6PD RDT) intended for use at point-of-care in impoverished rural settings where most malaria patients live, was evaluated. Methodology/Principal Findings This device and the standard qualitative fluorescent spot test (FST) were each compared against the quantitative spectrophotometric assay for G6PD activity as the diagnostic gold standard. The assessment occurred at meso-endemic Panenggo Ede in western Sumba Island in eastern Indonesia, where 610 residents provided venous blood. The G6PD RDT and FST qualitative assessments were performed in the field, whereas the quantitative assay was performed in a research laboratory at Jakarta. The median G6PD activity ≥5 U/gHb was 9.7 U/gHb and was considered 100% of normal activity. The prevalence of G6PD deficiency by quantitative assessment (<5 U/gHb) was 7.2%. Applying 30% of normal G6PD activity as the cut-off for qualitative testing, the sensitivity, specificity, positive predictive value, and negative predictive value for G6PD RDT versus FST among males were as follows: 100%, 98.7%, 89%, and 100% versus 91.7%, 92%, 55%, and 99%; P = 0.49, 0.001, 0.004, and 0.24, respectively. These values among females were: 83%, 92.7%, 17%, and 99.7% versus 100%, 92%, 18%, and 100%; P = 1.0, 0.89, 1.0 and 1.0, respectively. Conclusions/Significance The overall performance of G6PD RDT, especially 100% negative predictive value, demonstrates suitable safety for G6PD screening prior to administering hemolytic drugs like primaquine and many others. Relatively poor diagnostic performance

  2. Assessment of Point-of-Care Diagnostics for G6PD Deficiency in Malaria Endemic Rural Eastern Indonesia.

    PubMed

    Satyagraha, Ari W; Sadhewa, Arkasha; Elvira, Rosalie; Elyazar, Iqbal; Feriandika, Denny; Antonjaya, Ungke; Oyong, Damian; Subekti, Decy; Rozi, Ismail E; Domingo, Gonzalo J; Harahap, Alida R; Baird, J Kevin

    2016-02-01

    Patients infected by Plasmodium vivax or Plasmodium ovale suffer repeated clinical attacks without primaquine therapy against latent stages in liver. Primaquine causes seriously threatening acute hemolytic anemia in patients having inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency. Access to safe primaquine therapy hinges upon the ability to confirm G6PD normal status. CareStart G6PD, a qualitative G6PD rapid diagnostic test (G6PD RDT) intended for use at point-of-care in impoverished rural settings where most malaria patients live, was evaluated. This device and the standard qualitative fluorescent spot test (FST) were each compared against the quantitative spectrophotometric assay for G6PD activity as the diagnostic gold standard. The assessment occurred at meso-endemic Panenggo Ede in western Sumba Island in eastern Indonesia, where 610 residents provided venous blood. The G6PD RDT and FST qualitative assessments were performed in the field, whereas the quantitative assay was performed in a research laboratory at Jakarta. The median G6PD activity ≥ 5 U/gHb was 9.7 U/gHb and was considered 100% of normal activity. The prevalence of G6PD deficiency by quantitative assessment (<5 U/gHb) was 7.2%. Applying 30% of normal G6PD activity as the cut-off for qualitative testing, the sensitivity, specificity, positive predictive value, and negative predictive value for G6PD RDT versus FST among males were as follows: 100%, 98.7%, 89%, and 100% versus 91.7%, 92%, 55%, and 99%; P = 0.49, 0.001, 0.004, and 0.24, respectively. These values among females were: 83%, 92.7%, 17%, and 99.7% versus 100%, 92%, 18%, and 100%; P = 1.0, 0.89, 1.0 and 1.0, respectively. The overall performance of G6PD RDT, especially 100% negative predictive value, demonstrates suitable safety for G6PD screening prior to administering hemolytic drugs like primaquine and many others. Relatively poor diagnostic performance among females due to mosaic G6PD phenotype is an inherent limitation

  3. G6PD Deficiency (Glucose-6-Phosphate Dehydrogenase) (For Parents)

    MedlinePlus

    ... trigger, is removed. In rare cases, G6PD deficiency leads to chronic anemia . With the right precautions, a child with G6PD deficiency can lead a healthy and active life. About G6PD Deficiency ...

  4. G6PD Viangchan and G6PD Mediterranean are the main variants in G6PD deficiency in the Malay population of Malaysia.

    PubMed

    Yusoff, Narazah Mohd; Shirakawa, Taku; Nishiyama, Kaoro; Ee, Choo Keng; Isa, Mohd Nizam; Matsuo, Masafumi

    2003-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked red blood cell enzymopathy common in malaria endemic areas. Individuals affected by this disease show a wide variety of clinical signs of acute hemolytic anemia. Mutations of the G6PD gene in the Malay population with G6PD deficiency in Kelantan, a state in North East Malaysia were studied. Ninety-three individuals with G6PD deficiency were subjected to mutation analysis of the G6PD gene using polymerase chain reaction based techniques of multiplex PCR. Of the ninety-three DNA samples studied, molecular defects were identified in 80 cases (86%). Variants were heterogeneous - 28.7% were found to have a G to A nucleotide change at nucleotide 871 of the G6PD gene (G871A), corresponding to G6PD Viangchan. The other major mutations were G6PD Mediterranean, G6PD Vanua Lava, G6PD Coimbra, G6PD Kaiping, G6PD Orissa, G6PD Mahidol, G6PD Canton and G6PD Chatham. These results showed that there are heterogeneous mutations of the G6PD gene associated with G6PD deficiency and that G6PD Viangchan and G6PD Mediterranean account for the main variants in G6PD deficiency among the Malay population in Malaysia.

  5. G6PD Deficiency (Glucose-6-Phosphate Dehydrogenase) (For Parents)

    MedlinePlus

    ... are high-risk areas for the infectious disease malaria . Researchers have found evidence that the parasite that ... deficiency may have developed as a protection against malaria. continue G6PD Deficiency Symptom Triggers Kids with G6PD ...

  6. Neonatal nucleated red blood cells in G6PD deficiency.

    PubMed

    Yeruchimovich, Mark; Shapira, Boris; Mimouni, Francis B; Dollberg, Shaul

    2002-05-01

    The objective of this study is to study the absolute number of nucleated red blood cells (RBC) at birth, an index of active fetal erythropoiesis, in infants with G6PD deficiency and in controls. We tested the hypothesis that hematocrit and hemoglobin would be lower, and absolute nucleated RBC counts higher, in the G6PD deficient and that these changes would be more prominent in infants exposed passively to fava bean through maternal diet. Thirty-two term infants with G6PD deficiency were compared with 30 term controls. Complete blood counts with manual differential counts were obtained within 12 hours of life. Absolute nucleated RBC and corrected leukocyte counts were computed from the Coulter results and the differential count. G6PD deficient patients did not differ from controls in terms of gestational age, birth weight, or Apgar scores or in any of the hematologic parameters studied, whether or not the mother reported fava beans consumption in the days prior to delivery. Although intrauterine hemolysis is possible in G6PD deficient fetuses exposed passively to fava beans, our study supports that such events must be very rare.

  7. On the relation between malaria and G-6-PD deficiency

    PubMed Central

    Bottini, E.; Gloria-Bottini, F.; Maggioni, G.

    1978-01-01

    On the basis of the hypothesis that in the regions where favism is present a high correlation exists between endemic malaria and the frequency of G-6-PD deficiency, Huheey and Martin (1975) in a recent paper suggest that the haemolytic event in a malarial environment is a favourable selective factor. Therefore, the fitness of the G-6-PD-deficient individual who shows haemolysis is higher than that of those who do not show haemolysis. Modiano (1976) also suggested that haemolysis may not be a negative component of the selective forces which act on the G-6-PD-deficient variants. In this paper, some facts which make these hypotheses unlikely are considered. Other, more promising, lines for the analysis of the complex relation between malaria and G-6-PD deficiency are suggested. In Sardinia and in the area of the Po Delta, even though favism is present, there is a very low correlation between the frequency of G-6-PD deficiency and past malarial morbidity. Therefore, the situation is similar to that observed in other parts of the world, in which malaria is highly endemic, but where favism is absent. The following facts seem to be in contrast with the possibility that haemolysis could `by itself' be a favourable event: (1) In the hemizygous male, haemolysis due to favism is generally severe and there is a high mortality rate; (2) In the heterozygous female, the erythrocytes with G-6-PD deficiency seem to show a low parasite rate compared to normal cells, and it is just these erythrocytes that are destroyed during the haemolytic crisis; (3) In malarial environments, enzymopenic variants associated with continuous haemolysis have not been selected. A positive selection of such variants would be expected if haemolysis was `by itself' a positive factor. Several observations suggest that the G-6-PD system interacts with various factors, both genetical (thalassaemia, erythrocyte acid phosphatase, adenosine deaminase) and environmental (Vicia Faba, altitude, viral and protozoal

  8. Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers.

    PubMed

    Rueangweerayut, Ronnatrai; Bancone, Germana; Harrell, Emma J; Beelen, Andrew P; Kongpatanakul, Supornchai; Möhrle, Jörg J; Rousell, Vicki; Mohamed, Khadeeja; Qureshi, Ammar; Narayan, Sushma; Yubon, Nushara; Miller, Ann; Nosten, François H; Luzzatto, Lucio; Duparc, Stephan; Kleim, Jörg-Peter; Green, Justin A

    2017-07-24

    Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in Plasmodium vivax malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the Mahidol(487A) glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40-60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days). All participants had pretreatment hemoglobin levels ≥ 12.0 g/dL. Tafenoquine dose escalation stopped when hemoglobin decreased by ≥ 2.5 g/dL (or hematocrit decline ≥ 7.5%) versus pretreatment values in ≥ 3/6 subjects. A dose-response was evident in G6PD-heterozygous subjects (N = 15) receiving tafenoquine for the maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines were similar for tafenoquine 300 mg (-2.65 to -2.95 g/dL [N = 3]) and primaquine (-1.25 to -3.0 g/dL [N = 5]). Two further cohorts of G6PD-heterozygous subjects with G6PD enzyme levels 61-80% (N = 2) and > 80% (N = 5) of the site median normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD enzyme activities. Tafenoquine hemolytic potential was dose dependent, and hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme activity levels. Single-dose tafenoquine 300 mg did not appear to increase the severity of hemolysis versus primaquine 15 mg × 14 days.

  9. Thalassemia and G-6-PD Deficiency in Chinese-Canadians

    PubMed Central

    Gray, G. R.; Marion, R. B.

    1971-01-01

    Admission screening was performed on 684 Chinese-Canadian patients for thalassemia, abnormal hemoglobins and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Thirty-six healthy Chinese adults were also studied. The incidence of beta-thalassemia minor (hemoglobin A2 greater than 3.5%) was 3.8%. Presumptive alpha-thalassemia minor (demonstration of occasional red cells containing hemoglobin H inclusion bodies) was found in 6.7%. Two patients had findings consistent with alpha-beta-thalassemia. The incidence of G-6-PD deficiency (abnormal methemoglobin reduction test) in adult males was 4.7%. In a parallel study the incidence of hemoglobin Bart's in 310 Chinese newborns was 6.8%. Two mutant hemoglobins were found — hemoglobin E and hemoglobin J (Bangkok). PMID:5563348

  10. G6PD Deficiency Does Not Enhance Susceptibility for Acquiring Helicobacter pylori Infection in Sardinian Patients

    PubMed Central

    Dore, Maria Pina; Marras, Giuseppina; Rocchi, Chiara; Soro, Sara

    2016-01-01

    Background Subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more susceptible to infections due to impaired leukocyte bactericidal activity. The disorder is common in the Mediterranean area. The aim of this study was to investigate whether G6PD deficiency may be a risk factor for acquiring H. pylori infection. Methods We performed a retrospective study. Data from clinical records of 6565 patients (2278 men and 4287 women, median age 51, range 7‒94) who underwent upper endoscopy between 2002 and 2014 were collected. H. pylori status, assessed by histology plus rapid urease test or 13C-urea breath test, and G6PD status were also reported. A multiple logistic regression model was used to investigate the association between G6PD deficiency and H. pylori infection. Results Enzyme deficiency was detected in 12% (789/6565) of the entire cohort, and more specifically in 8.3% of men and in 14.0% of women. Overall, the proportion of patients positive for H. pylori was 50.6% and 51.5% among G6PD deficient and non-deficient patients (χ² = 0.271; p = 0.315). Moreover, among G6PD-deficient and normal patients the frequency of previous H. pylori infection was similar. After adjustment for age and gender the risk for acquiring H. pylori infection was similar in G6PD-deficient and normal patients. Only age was a strong statistically significant risk predictor. Conclusions These results demonstrate for the first time that G6PD deficiency does not enhance patients’ susceptibility to acquire H. pylori infection in Sardinia. PMID:27467818

  11. G6PD deficiency: global distribution, genetic variants and primaquine therapy.

    PubMed

    Howes, Rosalind E; Battle, Katherine E; Satyagraha, Ari W; Baird, J Kevin; Hay, Simon I

    2013-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) is a potentially pathogenic inherited enzyme abnormality and, similar to other human red blood cell polymorphisms, is particularly prevalent in historically malaria endemic countries. The spatial extent of Plasmodium vivax malaria overlaps widely with that of G6PD deficiency; unfortunately the only drug licensed for the radical cure and relapse prevention of P. vivax, primaquine, can trigger severe haemolytic anaemia in G6PD deficient individuals. This chapter reviews the past and current data on this unique pharmacogenetic association, which is becoming increasingly important as several nations now consider strategies to eliminate malaria transmission rather than control its clinical burden. G6PD deficiency is a highly variable disorder, in terms of spatial heterogeneity in prevalence and molecular variants, as well as its interactions with P. vivax and primaquine. Consideration of factors including aspects of basic physiology, diagnosis, and clinical triggers of primaquine-induced haemolysis is required to assess the risks and benefits of applying primaquine in various geographic and demographic settings. Given that haemolytically toxic antirelapse drugs will likely be the only therapeutic options for the coming decade, it is clear that we need to understand in depth G6PD deficiency and primaquine-induced haemolysis to determine safe and effective therapeutic strategies to overcome this hurdle and achieve malaria elimination.

  12. Markers of oxidative stress in umbilical cord blood from G6PD deficient African newborns

    PubMed Central

    Bengo, Derrick; Cusick, Sarah E.; Ndidde, Susan; Slusher, Tina M.

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that affects as many as 400 million people worldwide, making it the most common enzymatic defect. Subjects with G6PD deficiency are more likely to develop neonatal hyperbilirubinemia potentially leading to kernicterus and are at increased risk for acute hemolytic anemia when exposed to pro-oxidant compounds such as anti-malarial drugs. We collected umbilical cord blood from 300 males born in Uganda to assess for novel markers of systemic oxidative stress. We determined that 10.7% of the samples collected were G6PD A- deficient (G202A/A376G) and when these were compared with unaffected controls, there was significantly higher 8-hydroxy-2’-deoxyguanosine (8-OHdG) concentration, elevated ferritin, increased leukocyte count and higher small molecule antioxidant capacity. These data suggest increased baseline oxidative stress and an elevated antioxidant response in umbilical cord blood of patients with G6PD deficiency. PMID:28235023

  13. The G6PD flow-cytometric assay is a reliable tool for diagnosis of G6PD deficiency in women and anaemic subjects.

    PubMed

    Bancone, Germana; Kalnoky, Michael; Chu, Cindy S; Chowwiwat, Nongnud; Kahn, Maria; Malleret, Benoit; Wilaisrisak, Pornpimon; Rénia, Laurent; Domingo, Gonzalo J; Nosten, Francois

    2017-08-29

    Glucose-6-phosphate dehydrogenase (G6PD) activity is essential for redox equilibrium of red blood cells (RBCs) and, when compromised, the RBCs are more susceptible to haemolysis. 8-aminoquinolines (primaquine and tafenoquine) are used for the radical curative treatment of Plasmodium vivax malaria and can cause haemolysis in G6PD deficient subjects. Haemolytic risk is dependent on treatment dose and patient G6PD status but ultimately it correlates with the number of G6PD deficient RBCs. The G6PD spectrophotometric assay reliably identifies deficient subjects but is less reliable in heterozygous females, especially when other blood conditions are present. In this work we analysed samples with a range of G6PD phenotypes and haematologic conditions from 243 healthy volunteers of Asian or African-American heritage using both the spectrophotomeric assay and the G6PD flow-cytometric assay. Overall 18.5% of subjects (29.3% of Asian females) presented with anaemia, associated with decreased RBCs volume (MCV) and reticulocytosis; the flow-cytometric assay showed good correlation with the spectrophotometric assay (Pearson's r 0.918-0.957) and was less influenced by haemoglobin concentration, number of RBCs and number of reticulocytes. This resulted in more precise quantification of the number of G6PD deficient RBCs and presumably higher predictive power of drug induced haemolytic risk.

  14. Molecular characterization of a German variant of glucose-6-phosphate dehydrogenase deficiency (G6PD Aachen).

    PubMed

    Efferth, T; Osieka, R; Beutler, E

    2000-02-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-chromosome-linked hereditary disorder. Clinically, patients with G6PD deficiency often present with drug- or food-induced hemolytic crises or neonatal jaundice. G6PD is involved in the generation of NADPH and reduced glutathione. In contrast to American, Mediterranean, and African ancestries, only few variants are known from Middle and Northern Europe. We describe the molecular characterization of a distinct variant from the northwestern area of Germany, G6PD Aachen. The sequence of the G6PD gene from three afflicted males was found to be hemizygous at cDNA residue 1089 for a C-->G mutation with a predicted amino acid change of Asn363Lys. The 1089 C-->G point mutation is unique, but produces the identical amino acid change found in a Mexican variant of G6PD deficiency, G6PD Loma Linda. This G6PD-deficient variant is caused by a 1089 C-->A mutation. The 363-amino-acid replacement is located outside a known mutation cluster region between amino acid residues 380 and 450, but may disrupt or weaken dimer interactions of G6PD enzyme subunits.

  15. Glucose-6-phosphate dehydrogenase deficiency (G6PD) as a risk factor of male neonatal sepsis.

    PubMed

    Rostami-Far, Z; Ghadiri, K; Rostami-Far, M; Shaveisi-Zadeh, F; Amiri, A; Rahimian Zarif, B

    2016-01-01

    Introduction.Neonatal sepsis is a disease process, which represents the systemic response of bacteria entering the bloodstream during the first 28 days of life. The prevalence of sepsis is higher in male infants than in females, but the exact cause is unknown. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway, which leads to the production of NADPH. NADPH is required for the respiratory burst reaction in white blood cells (WBCs) to destroy microorganisms. The purpose of this study was to evaluate the prevalence of G6PD deficiency in neonates with sepsis. Materials and methods.This study was performed on 76 neonates with sepsis and 1214 normal neonates from February 2012 to November 2014 in the west of Iran. The G6PD deficiency status was determined by fluorescent spot test. WBCs number and neutrophils percentages were measured and compared in patients with and without G6PD deficiency. Results.The prevalence of the G6PD deficiency in neonates with sepsis was significantly higher compared to the control group (p=0.03). WBCs number and neutrophils percentages in G6PD deficient patients compared with patients without G6PD deficiency were decreased, but were not statistically significant (p=0.77 and p=0.86 respectively). Conclusions.G6PD deficiency is a risk factor of neonatal sepsis and also a justification for more male involvement in this disease. Therefore, newborn screening for this disorder is recommended.

  16. Spatial distribution of G6PD deficiency variants across malaria-endemic regions

    PubMed Central

    2013-01-01

    Background Primaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax. It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission. However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquine’s widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis. The risk of such an outcome varies widely among G6PD gene variants. Methods A literature review was conducted to identify surveys of G6PD variant frequencies among representative population groups. Informative surveys were assembled into two map series: (1) those showing the relative proportions of the different variants among G6PDd individuals; and (2) those showing allele frequencies of G6PD variants based on population surveys without prior G6PDd screening. Results Variants showed conspicuous geographic patterns. A limited repertoire of variants was tested for across sub-Saharan Africa, which nevertheless indicated low genetic heterogeneity predominated by the G6PD A- 202A mutation, though other mutations were common in western Africa. The severe G6PD Mediterranean variant was widespread across western Asia. Further east, a sharp shift in variants was identified, with high variant heterogeneity in the populations of China and the Asia-Pacific where no single variant dominated. Conclusions G6PD variants exhibited distinctive region-specific distributions with important primaquine policy implications. Relative homogeneity in the Americas, Africa, and western Asia contrasted sharply with the heterogeneity of variants in China, Southeast Asia and Oceania. These findings will inform rational risk assessments for primaquine in developing public health strategies for malaria control

  17. Does G6PD deficiency protect against cancer? A critical review.

    PubMed Central

    Cocco, P

    1987-01-01

    Previous observations on the lower mortality for cancer experienced in populations with a higher frequency of G6PD deficiency support biochemical studies on the role of G6PD during cell proliferation. The general agreement among experimental studies prevented a deeper analysis of the sources of what has been called "epidemiological evidence of the protective role of G6PD deficiency against cancer". This review analyses the methods and findings in those papers, stressing their limitations and emphasising that no final conclusions can be drawn from them. Preliminary results of ongoing epidemiological studies of G6PD deficiency and cancer are presented, although they do not prove or disprove the hypothesis that G6PD deficiency protects against cancer. PMID:3309118

  18. G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study

    PubMed Central

    Ley, Benedikt; Alam, Mohammad Shafiul; Thriemer, Kamala; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Auburn, Sarah; Poirot, Eugenie; Price, Ric N.; Khan, Wasif Ali

    2016-01-01

    Background The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy. Methods Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0–2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0–2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374). Results Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2–27.3) hours for P. falciparum, 20.0 (IQR: 9.5–22.7) hours for P. vivax and 16.6 (IQR: 10.0–46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (<10% activity), five participants (5/174) had mild G6PD deficiency (10–60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively. Conclusion The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal

  19. Prevalence and molecular study of G6PD deficiency in Malaysian Orang Asli.

    PubMed

    Amini, F; Ismail, E; Zilfalil, B-A

    2011-04-01

    This study aims to define the prevalence and the molecular basis of G6PD deficiency in the Negrito tribe of the Malaysian Orang Asli. Four hundred and eighty seven consenting Negrito volunteers were screened for G6PD deficiency through the use of a fluorescent spot test. DNA from deficient individuals underwent PCR-RFLP analysis using thirteen recognized G6PD mutations. In the instances when the mutation could not be identified by PCR-RFLP, the entire coding region of the G6PD gene was subjected to DNA sequencing. In total, 9% (44/486) of the sample were found to be G6PD-deficient. However, only 25 samples were subjected to PCR-RFLP and DNA sequencing. Of these, three were found to carry Viangchan, one Coimbra and 16, a combination of C1311T in exon 11 and IVS11 T93C. Mutation(s) for the five remaining samples are unknown. The mean G6PD enzyme activity ranged 5.7 IU/gHb in deficient individuals. Our results demonstrate that the frequency of G6PD deficiency is higher among the Negrito Orang Asli than other Malaysian races. The dual presence of C1311T and IVS11 T93C in 64% of the deficient individuals (16/44) could well be a result of genetic drift within this isolated group. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  20. Performance of BinaxNOW G6PD Deficiency Point-of-Care Diagnostic in P. vivax-Infected Subjects

    PubMed Central

    Osorio, Lyda; Carter, Nick; Arthur, Preetam; Bancone, Germana; Gopalan, Sowmya; Gupta, Sandeep K.; Noedl, Harald; Kochar, Sanjay K.; Kochar, Dhanpat K.; Krudsood, Srivicha; Lacerda, Marcus V.; Llanos-Cuentas, Alejandro; Rueangweerayut, Ronnatrai; Srinivasan, Ramadurai; Treiber, Moritz; Möhrle, Jörg J.; Green, Justin

    2015-01-01

    Accurate diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is required to avoid the risk of acute hemolysis associated with 8-aminoquinoline treatment. The performance of the BinaxNOW G6PD test compared with the quantitative spectrophotometric analysis of G6PD activity was assessed in 356 Plasmodium vivax-infected subjects in Brazil, Peru, Thailand, and India. In the quantitative assay, the median G6PD activity was 8.81 U/g hemoglobin (range = 0.05–20.19), with 11 (3%) subjects identified as deficient. Sensitivity of the BinaxNOW G6PD to detect deficient subjects was 54.5% (6 of 11), and specificity was 100% (345 of 345). Room temperatures inadvertently falling outside the range required to perform the rapid test (18–25°C) together with subtlety of color change and insufficient training could partially explain the low sensitivity found. Ensuring safe use of 8-aminoquinolines depends on additional development of simple, highly sensitive G6PD deficiency diagnostic tests suitable for routine use in malaria-endemic areas. PMID:25385861

  1. G6PD Deficiency in an HIV Clinic Setting in the Dominican Republic.

    PubMed

    Xu, Julia Z; Francis, Richard O; Lerebours Nadal, Leonel E; Shirazi, Maryam; Jobanputra, Vaidehi; Hod, Eldad A; Jhang, Jeffrey S; Stotler, Brie A; Spitalnik, Steven L; Nicholas, Stephen W

    2015-10-01

    Because human immunodeficiency virus (HIV)-infected patients receive prophylaxis with oxidative drugs, those with glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience hemolysis. However, G6PD deficiency has not been studied in the Dominican Republic, where many individuals have African ancestry. Our objective was to determine the prevalence of G6PD deficiency in Dominican HIV-infected patients and to attempt to develop a cost-effective algorithm for identifying such individuals. To this end, histories, chart reviews, and G6PD testing were performed for 238 consecutive HIV-infected adult clinic patients. The overall prevalence of G6PD deficiency (8.8%) was similar in males (9.3%) and females (8.5%), and higher in Haitians (18%) than Dominicans (6.4%; P = 0.01). By logistic regression, three clinical variables predicted G6PD status: maternal country of birth (P = 0.01) and a history of hemolysis (P = 0.01) or severe anemia (P = 0.03). Using these criteria, an algorithm was developed, in which a patient subset was identified that would benefit most from G6PD screening, yielding a sensitivity of 94.7% and a specificity of 97.2%, increasing the pretest probability (8.8-15.1%), and halving the number of patients needing testing. This algorithm may provide a cost-effective strategy for improving care in resource-limited settings. © The American Society of Tropical Medicine and Hygiene.

  2. G6PD Deficiency in an HIV Clinic Setting in the Dominican Republic

    PubMed Central

    Xu, Julia Z.; Francis, Richard O.; Lerebours Nadal, Leonel E.; Shirazi, Maryam; Jobanputra, Vaidehi; Hod, Eldad A.; Jhang, Jeffrey S.; Stotler, Brie A.; Spitalnik, Steven L.; Nicholas, Stephen W.

    2015-01-01

    Because human immunodeficiency virus (HIV)-infected patients receive prophylaxis with oxidative drugs, those with glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience hemolysis. However, G6PD deficiency has not been studied in the Dominican Republic, where many individuals have African ancestry. Our objective was to determine the prevalence of G6PD deficiency in Dominican HIV-infected patients and to attempt to develop a cost-effective algorithm for identifying such individuals. To this end, histories, chart reviews, and G6PD testing were performed for 238 consecutive HIV-infected adult clinic patients. The overall prevalence of G6PD deficiency (8.8%) was similar in males (9.3%) and females (8.5%), and higher in Haitians (18%) than Dominicans (6.4%; P = 0.01). By logistic regression, three clinical variables predicted G6PD status: maternal country of birth (P = 0.01) and a history of hemolysis (P = 0.01) or severe anemia (P = 0.03). Using these criteria, an algorithm was developed, in which a patient subset was identified that would benefit most from G6PD screening, yielding a sensitivity of 94.7% and a specificity of 97.2%, increasing the pretest probability (8.8–15.1%), and halving the number of patients needing testing. This algorithm may provide a cost-effective strategy for improving care in resource-limited settings. PMID:26240158

  3. G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications

    PubMed Central

    Luzzatto, Lucio; Seneca, Elisa

    2014-01-01

    That primaquine and other drugs can trigger acute haemolytic anaemia in subjects who have an inherited mutation of the glucose 6-phosphate dehydrogenase (G6PD) gene has been known for over half a century: however, these events still occur, because when giving the drug either the G6PD status of a person is not known, or the risk of this potentially life-threatening complication is under-estimated. Here we review briefly the genetic basis of G6PD deficiency, and then the pathophysiology and the clinical features of drug-induced haemolysis; we also update the list of potentially haemolytic drugs (which includes rasburicase). It is now clear that it is not good practice to give one of these drugs before testing a person for his/her G6PD status, especially in populations in whom G6PD deficiency is common. We discuss therefore how G6PD testing can be done reconciling safety with cost; this is once again becoming of public health importance, as more countries are moving along the pathway of malaria elimination, that might require mass administration of primaquine. Finally, we sketch the triangular relationship between malaria, antimalarials such as primaquine, and G6PD deficiency: which is to some extent protective against malaria, but also a genetically determined hazard when taking primaquine. PMID:24372186

  4. G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications.

    PubMed

    Luzzatto, Lucio; Seneca, Elisa

    2014-02-01

    That primaquine and other drugs can trigger acute haemolytic anaemia in subjects who have an inherited mutation of the glucose 6-phosphate dehydrogenase (G6PD) gene has been known for over half a century: however, these events still occur, because when giving the drug either the G6PD status of a person is not known, or the risk of this potentially life-threatening complication is under-estimated. Here we review briefly the genetic basis of G6PD deficiency, and then the pathophysiology and the clinical features of drug-induced haemolysis; we also update the list of potentially haemolytic drugs (which includes rasburicase). It is now clear that it is not good practice to give one of these drugs before testing a person for his/her G6PD status, especially in populations in whom G6PD deficiency is common. We discuss therefore how G6PD testing can be done reconciling safety with cost; this is once again becoming of public health importance, as more countries are moving along the pathway of malaria elimination, that might require mass administration of primaquine. Finally, we sketch the triangular relationship between malaria, antimalarials such as primaquine, and G6PD deficiency: which is to some extent protective against malaria, but also a genetically determined hazard when taking primaquine.

  5. Attempts to validate a possible predictive animal model for human erythrocyte G-6-PD deficiency

    SciTech Connect

    Horton, H.M.; Calabrese, E.J.

    1986-01-01

    The use of Dorset sheep erythrocytes as a model for human G-6-PD deficient erythrocytes was investigated. Seven pharmaceuticals were examined for oxidant stressor effects using a liver microsomal enzyme system to generate metabolites of the drugs. The pharmaceuticals examined were salicyclic acid, dapsone, naphthalene, B-naphtol, p-aminobenzoic acid, sulfanilamide and sulfapyridine. The test compounds were incubated with Dorset sheep erythrocytes and oxidant stressor effects were measured through reduced glutathione (GSH) levels and methemaglobin formation. The response of the Dorset sheep erythrocytes to the seven agents was compared to previous studies revealing the response of human G-6-PD deficient erythrocytes to these agents. The results indicated that metabolites of the pharmaceuticals, B-naphthol, dapsone, and sulfanilamide, are oxidant stressor agents towards sheep G-6-PD deficient erythrocytes. These results agreed with studies on the response of human G-6-PD deficient erythrocytes. The metabolized naphthalene and sulfapyridine did not cause oxidant stress in the sheep erythrocytes, despite the fact that these two agents caused oxidizing effects in human G-6-PD deficient erythrocytes in previous studies. None of the non-metabolized parent compounds caused oxidant stress in the sheep erythrocytes, which agreed with the responses of human G-6-PD deficient erythrocytes.

  6. Prevalence of G6PD deficiency in Iran, a mata-analysis.

    PubMed

    Moosazadeh, Mahmood; Amiresmaili, Mohammadreza; Aliramezany, Maryam

    2014-01-01

    Search results show that numerous primary studies have been carried out in different parts of Iran regarding prevalence of G6PD deficiency; if results of these studies are combined, a reliable estimation of prevalence of this factor will be achieved in Iran. Thus, present study, aimed to determine the prevalence of G6PD deficiency by combining findings of qualified primary studies using meta-analysis and taking into account heterogeneity considerations. Searching the relevant keywords in Iranian and International databases, primary studies were selected. After quality appraisal and applying inclusion and exclusion criteria, relevant primary studies were selected. In each study, standard error of prevalence of G6PD was calculated according to binominal distribution formula. Finally, heterogeneity index was determined among studies using Cochran's test. Prevalence of G6PD in Iran was estimated by STATA software ver 11 using fixed or random effect model based on heterogeneity results. 148916 subjects in 36 primary studies which entered this meta-analysis were examined. G6PD deficiency prevalence was 6.7% in Iran (men: 8.8% and women: 2.2%). Also, this deficiency in the present study was four times higher in men than in women. Its prevalence was adjusted in different parts of Iran and it was shown that it was between 0.8 and 15.2 using Bayesian analysis. This meta-analysis showed that Iran is among countries with high frequency of G6PD deficiency and there is a significant difference in prevalence of G6PD in different parts of Iran. According to these results, screening newborn children seems very vital. Carrying out other primary studies regarding prevalence of G6PD seems unnecessary.

  7. Modelling primaquine-induced haemolysis in G6PD deficiency

    PubMed Central

    Watson, James; Taylor, Walter RJ; Menard, Didier; Kheng, Sim; White, Nicholas J

    2017-01-01

    Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable, this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0.75 mg/kg regimen for G6PDd. The model suggests that a step-wise increase in daily administered primaquine dose would be relatively safe in G6PDd. If this is confirmed, then were this regimen to be recommended for radical cure patients would not require testing for G6PDd in areas where G6PDd Viangchan or milder variants are prevalent. DOI: http://dx.doi.org/10.7554/eLife.23061.001 PMID:28155819

  8. G6PD Deficiency and Hemoglobinopathies: Molecular Epidemiological Characteristics and Healthy Effects on Malaria Endemic Bioko Island, Equatorial Guinea

    PubMed Central

    Lin, Min; Yang, Li Ye; Xie, Dong De; Chen, Jiang Tao; Nguba, Santiago-m Monte; Ehapo, Carlos Sala; Zhan, Xiao Fen; Eyi, Juan Urbano Monsuy; Matesa, Rocio Apicante; Obono, Maximo Miko Ondo; Yang, Hui; Yang, Hui Tian; Cheng, Ji Dong

    2015-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobinopathies were the inherited conditions found mostly in African. However, few epidemiological data of these disorders was reported in Equatorial Guinea (EQG). This study aimed to assess the prevalence and healthy effects of G6PD deficiency and hemoglobinopathies among the people on malaria endemic Bioko Island, EQG. Materials and Methods Blood samples from 4,144 unrelated subjects were analyzed for G6PD deficieny by fluorescence spot test (FST), high-resolution melting assay and PCR-DNA sequencing. In addition, 1,186 samples were randomly selected from the 4,144 subjects for detection of hemoglobin S (HbS), HbC, and α-thalassemia deletion by complete blood count, PCR-DNA sequencing and reverse dot blot (RDB). Results The prevalence of malaria and anemia was 12.6% (522/4,144) and 32.8% (389/1,186), respectively. Overall, 8.7% subjects (359/4,144) were G6PD-deficient by FST, including 9.0% (249/2,758) males and 7.9% (110/1,386) females. Among the 359 G6PD-deficient individuals molecularly studied, the G6PD A- (G202A/A376G) were detected in 356 cases (99.2%), G6PD Betica (T968C/A376G) in 3 cases. Among the 1,186 subjects, 201 cases were HbS heterozygotes, 35 cases were HbC heterozygotes, and 2 cases were HbCS double heterozygotes; 452 cases showed heterozygous α-thalassemia 3.7 kb deletion (-α3.7 kb deletion) and 85 homozygous - α3.7 kb deletion. The overall allele frequencies were HbS 17.1% (203/1186); HbC, 3.1% (37/1186); and –α3.7 kb deletion 52.4% (622/1186), respectively. Conclusions High G6PD deficiency in this population indicate that diagnosis and management of G6PD deficiency is necessary on Bioko Island. Obligatory newborn screening, prenatal screening and counseling for these genetic disorders, especially HbS, are needed on the island. PMID:25915902

  9. Adverse effects of herbal or dietary supplements in G6PD deficiency: a systematic review.

    PubMed

    Lee, Shaun Wen Huey; Lai, Nai Ming; Chaiyakunapruk, Nathorn; Chong, David Weng Kwai

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common genetic disorder, affecting nearly 400 million individuals worldwide. Whilst it is known that a number of drugs, foods and chemicals can trigger haemolysis in G6PD deficient individuals, the association between herbal and dietary supplements and haemolysis is less clear. The objective of this study was to evaluate the association between herbal or dietary supplements and adverse events in G6PD deficient individuals. We searched 14 electronic databases from their inception until November 2015 for articles describing the use of herbal or dietary supplements in G6PD deficient individuals. Additional publications were identified from manually searching textbooks, conference abstracts and the grey literature. All study designs were included as long as they contained clinical information. These gathered findings were summarized narratively. Thirty-two publications met inclusion criteria. These reported on 10 herbal and dietary supplements. Overall evidence linking haemolysis to a herbal/dietary supplement was only found for henna. No evidence of harm was observed for vitamin C, vitamin E, vitamin K, Gingko biloba and α-lipoic acid. The review showed that there was insufficient evidence to contravene the use of most herbal or dietary products at therapeutic doses in G6PD deficient subjects. © 2016 The British Pharmacological Society.

  10. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Rasburicase Therapy in the context of G6PD Deficiency Genotype

    PubMed Central

    Relling, Mary V.; McDonagh, Ellen M.; Chang, Tamara; Caudle, Kelly E.; McLeod, Howard L.; Haidar, Cyrine E.; Klein, Teri; Luzzatto, Lucio

    2014-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia (AHA) induced by a number of drugs. We provide guidance as to which G6PD genotypes are associated with G6PD deficiency in males and females. Rasburicase is contraindicated in G6PD deficient patients due to the risk of AHA and possibly methemoglobinemia. Unless preemptive genotyping has established a positive diagnosis of G6PD deficiency, quantitative enzyme assay remains the mainstay of screening prior to rasburicase use. PMID:24787449

  11. Red cell glucose 6-phosphate dehydrogenase deficiency in the northern region of Turkey: is G6PD deficiency exclusively a male disease?

    PubMed

    Albayrak, Canan; Albayrak, Davut

    2015-03-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis. However, this disease affects both males and females. In Turkey, the frequency of this enzyme deficiency was reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in the northern Black Sea region of Turkey is unknown. The aims of this study were to assess the prevalence of G6PD deficiency in the northern region Turkey in children and adults with hyperbilirubinemia and hemolytic anemia. This report included a total of 976 G6PD enzyme results that were analyzed between May 2005 and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD deficiency was significantly less frequent in females (1.9%, 6/323) than in males (6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia. In both the newborn group and the group of children, G6PD deficiency was significantly more frequent in males. In the combined group of children (groups I and II), the proportion of males was 74% and 67% in all groups (P = .0008). In conclusion, in northern region of Turkey, G6PD deficiency is an important cause of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This study suggests that most pediatricians thought that G6PD deficiency is exclusively a male disease. For this reason, some female patients may have been undiagnosed.

  12. G6PD deficiency and fava bean consumption do not produce hemolysis in Thailand.

    PubMed

    Kitayaporn, D; Charoenlarp, P; Pattaraarechachai, J; Pholpoti, T

    1991-06-01

    Favism, a hemolytic condition associated with fava bean consumption among the glucose-6-phosphate dehydrogenase (G6PD) deficient persons, is well described in the Middle East and Mediterranean areas. However, it is not well documented among the Thais or other Southeast Asians. It is possible that it does exist but that hemolysis which develops is of very minor degree and thus escapes clinical detection. This cross-sectional study hypothesizes that if the fava bean and G6PD deficiency interact in the Thai population, they should cause a significant difference in hematocrit level. The study was carried out in a community hospital in a malaria endemic area. We found that there was a trivial difference of the hematocrit (approximately 1%) which was too small to warrant any clinical significance after controlling for the extraneous effects of age, sex, use of malaria chemoprophylaxis, falciparum infection, use of analgesics/antipyretics and admission status of the patients (p = 0.668). This may be due to the presence of different G6PD mutants to those found elsewhere or due to different consumption patterns of fava beans among the Thais compared to people in other areas with high prevalence of G6PD deficiency.

  13. Prevalence of G6PD deficiency in selected populations from two previously high malaria endemic areas of Sri Lanka

    PubMed Central

    Kapilananda, G. M. G.; Samarakoon, Dilhani; Maddevithana, Sashika; Wijesundera, Sulochana; Goonaratne, Lallindra V.; Karunaweera, Nadira D.

    2017-01-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme deficiency is known to offer protection against malaria and an increased selection of mutant genes in malaria endemic regions is expected. However, anti-malarial drugs such as primaquine can cause haemolytic anaemia in persons with G6PD deficiency. We studied the extent of G6PD deficiency in selected persons attending Teaching Hospitals of Anuradhapura and Kurunegala, two previously high malaria endemic districts in Sri Lanka. A total of 2059 filter-paper blood spots collected between November 2013 and June 2014 were analysed for phenotypic G6PD deficiency using the modified WST-8/1-methoxy PMS method. Each assay was conducted with a set of controls and the colour development assessed visually as well as with a microplate reader at OD450-630nm. Overall, 142/1018 (13.95%) and 83/1041 (7.97%) were G6PD deficient in Anuradhapura and Kurunegala districts respectively. The G6PD prevalence was significantly greater in Anuradhapura when compared to Kurunegala (P<0.0001). Surprisingly, females were equally affected as males in each district: 35/313 (11.18%) males and 107/705 (15.18%) females were affected in Anuradhapura (P = 0.089); 25/313 (7.99%) males and 58/728 (7.97%) females were affected in Kurunegala (P = 0.991). Prevalence was greater among females in Anuradhapura than in Kurunegala (P<0.05), while no such difference was observed between the males (P>0.05). Severe deficiency (<10% normal) was seen among 28/1018 (2.75%) in Anuradhapura (7 males; 21 females) and 17/1041 (1.63%) in Kurunegala (7 males; 10 females). Enzyme activity between 10–30% was observed among 114/1018 (11.20%; 28 males; 86 females) in Anuradhapura while it was 66/1041 (6.34%; 18 males; 48 females) in Kurunegala. Screening and educational programmes for G6PD deficiency are warranted in these high risk areas irrespective of gender for the prevention of disease states related to this condition. PMID:28152025

  14. G6PD Deficiency at Sumba in Eastern Indonesia Is Prevalent, Diverse and Severe: Implications for Primaquine Therapy against Relapsing Vivax Malaria

    PubMed Central

    Satyagraha, Ari Winasti; Sadhewa, Arkasha; Baramuli, Vanessa; Elvira, Rosalie; Ridenour, Chase; Elyazar, Iqbal; Noviyanti, Rintis; Coutrier, Farah Novita; Harahap, Alida Roswita; Baird, J. Kevin

    2015-01-01

    Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity because hypnozoitocidal therapy against relapse requires primaquine, which causes a mild to severe acute hemolytic anemia in G6PD deficient patients. Many national malaria control programs recommend primaquine therapy without G6PD screening but with monitoring due to a broad lack of G6PD deficiency screening capacity. The degree of risk in doing so hinges upon the level of residual G6PD activity among the variants present in any given area. We conducted studies on Sumba Island in eastern Indonesia in order to assess the potential threat posed by primaquine therapy without G6PD screening. We sampled 2,033 residents of three separate districts in western Sumba for quantitative G6PD activity and 104 (5.1%) were phenotypically deficient (<4.6U/gHb; median normal 10U/gHb). The villages were in two distinct ecosystems, coastal and inland. A positive correlation occurred between the prevalence of malaria and G6PD deficiency: 5.9% coastal versus inland 0.2% for malaria (P<0.001), and 6.7% and 3.1% for G6PD deficiency (P<0.001) at coastal and inland sites, respectively. The dominant genotypes of G6PD deficiency were Vanua Lava, Viangchan, and Chatham, accounting for 98.5% of the 70 samples genotyped. Subjects expressing the dominant genotypes all had less than 10% of normal enzyme activities and were thus considered severe variants. Blind administration of anti-relapse primaquine therapy at Sumba would likely impose risk of serious harm. PMID:25746733

  15. Glucose-6-phosphate dehydrogenase (G6PD) deficiency among tribal populations of India - Country scenario.

    PubMed

    Mukherjee, Malay B; Colah, Roshan B; Martin, Snehal; Ghosh, Kanjaksha

    2015-05-01

    It is believed that the tribal people, who constitute 8.6 per cent of the total population (2011 census of India), are the original inhabitants of India. Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is an X-linked genetic defect, affecting around 400 million people worldwide and is characterized by considerable biochemical and molecular heterogeneity. Deficiency of this enzyme is highly polymorphic in those areas where malaria is/has been endemic. G6PD deficiency was reported from India more than 50 years ago. t0 he prevalence varies from 2.3 to 27.0 per cent with an overall prevalence of 7.7 per cent in different tribal groups. Since the tribal populations live in remote areas where malaria is/has been endemic, irrational use of antimalarial drugs could result in an increased number of cases with drug induced haemolysis. Therefore, before giving antimalarial therapy, routine screening for G6PD deficiency should be undertaken in those tribal communities where its prevalence is high.

  16. Acute haemolytic episodes & fava bean consumption in G6PD deficient Iraqis.

    PubMed

    Yahya, H I; al-Allawi, N A

    1993-12-01

    The relation between fava bean ingestion and the occurrence of a haemolytic episode was studied in 102 glucose-6-phosphate dehydrogenate (G6PD) deficient Iraqi patients. None of the patients (mean age 12.8 yr) had a documented similar illness earlier, although all of them gave history of reported regular fava bean ingestion in the past. Further, none of the three patients who were rechallenged (2-3 months later) by the beans developed any clinical or laboratory evidence of haemolysis. The incidence of the haemolytic episodes was found to peak in April, while the fava bean season extends from February to June. This study thus does not support a causal relation between the bean ingestion and the haemolytic episodes in G6PD deficient Iraqis. Possibly, some other factor such as a viral infection may be involved.

  17. Single Low Dose Primaquine (0.25mg/kg) Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects

    PubMed Central

    Bancone, Germana; Chowwiwat, Nongnud; Somsakchaicharoen, Raweewan; Poodpanya, Lalita; Moo, Paw Khu; Gornsawun, Gornpan; Kajeechiwa, Ladda; Thwin, May Myo; Rakthinthong, Santisuk; Nosten, Suphak; Thinraow, Suradet; Nyo, Slight Naw; Ling, Clare L.; Wiladphaingern, Jacher; Kiricharoen, Naw Lily; Moore, Kerryn A.; White, Nicholas J.; Nosten, Francois

    2016-01-01

    Background Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75mg/kg (adult dose 45mg) but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15–20%) in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25mg/kg (adult dose 15mg) to Artemisinin-based Combination Therapies (ACTs) without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant) approximates 15%. Methods and Findings The tolerability and safety of primaquine (single dose 0.25 mg base/kg) combined with dihydroartemisinin-piperaquine (DHA-PPQ) given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5

  18. Changes in red blood cell membrane structure in G6PD deficiency: an atomic force microscopy study.

    PubMed

    Tang, Jia; Jiang, Chengrui; Xiao, Xiao; Fang, Zishui; Li, Lei; Han, Luhao; Mei, Anqi; Feng, Yi; Guo, Yibin; Li, Hongyi; Jiang, Weiying

    2015-04-15

    Glucose-6-phosphate dehydrogenase deficiency affects over 400 million people worldwide. The hemolytic anemia in G6PD deficiency is usually triggered by oxidative stress, but the mechanism remains uncertain. We have used atomic force microscopy for studying changes in red blood cell membrane and providing new insights on the mechanism. G6PD activity assay and molecular genetic tests were used for molecular diagnosis. AFM was used to investigate alterations in the ultrastructure of G6PD deficient RBC membranes, the influence of different primaquine concentrations, and the protective effects of vitamin C. Nine variants were identified from 33 G6PD deficient individuals. AFM imaging and quantitative analysis showed that G6PD deficient erythrocytes became heterogeneous and roughness measurements of erythrocyte membranes are increased. G6PD enzyme activity and different mutations may relate with roughness parameters. Furthermore, primaquine induces an increased roughness and height of erythrocyte membrane. Meanwhile, primaquine induces damages to erythrocytes which could be prevented by vitamin C treatment in normal RBCs but not in G6PD deficient erythrocytes. Our research may give valuable information about the status of G6PD deficient patients and explore the mechanism of hemolytic anemia. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. G6pd Deficiency Does Not Affect the Cytosolic Glutathione or Thioredoxin Antioxidant Defense in Mouse Cochlea.

    PubMed

    White, Karessa; Kim, Mi-Jung; Ding, Dalian; Han, Chul; Park, Hyo-Jin; Meneses, Zaimary; Tanokura, Masaru; Linser, Paul; Salvi, Richard; Someya, Shinichi

    2017-06-07

    Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP(+) to NADPH and is thought to be the principal source of NADPH for the cytosolic glutathione and thioredoxin antioxidant defense systems. We investigated the roles of G6PD in the cytosolic antioxidant defense in the cochlea of G6pd hypomorphic mice that were backcrossed onto normal-hearing CBA/CaJ mice. Young G6pd-deficient mice displayed a significant decrease in cytosolic G6PD protein levels and activities in the inner ears. However, G6pd deficiency did not affect the cytosolic NADPH redox state, or glutathione or thioredoxin antioxidant defense in the inner ears. No histological abnormalities or oxidative damage was observed in the cochlea of G6pd hemizygous males or homozygous females. Furthermore, G6pd deficiency did not affect auditory brainstem response hearing thresholds, wave I amplitudes or wave I latencies in young males or females. In contrast, G6pd deficiency resulted in increased activities and protein levels of cytosolic isocitrate dehydrogenase 1, an enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate and NADP(+) to NADPH, in the inner ear. In a mouse inner ear cell line, knockdown of Idh1, but not G6pd, decreased cell growth rates, cytosolic NADPH levels, and thioredoxin reductase activities. Therefore, under normal physiological conditions, G6pd deficiency does not affect the cytosolic glutathione or thioredoxin antioxidant defense in mouse cochlea. Under G6pd deficiency conditions, isocitrate dehydrogenase 1 likely functions as the principal source of NADPH for cytosolic antioxidant defense in the cochlea.SIGNIFICANCE STATEMENT Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP(+) to NADPH and

  20. Chronic nonspherocytic hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency: report of two families with novel mutations causing G6PD Bangkok and G6PD Bangkok Noi.

    PubMed

    Tanphaichitr, Voravarn S; Hirono, Akira; Pung-amritt, Parichat; Treesucon, Ajjima; Wanachiwanawin, Wanchai

    2011-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common hereditary enzymopathies worldwide. Mostly G6PD deficient cases are asymptomatic though they may have the risk of neonatal jaundice (NNJ) and acute intravascular hemolysis during oxidative stress. Chronic nonspherocytic hemolytic anemia (CNSHA) due to G6PD deficiency is rare. In Thailand, one case was reported 40 years ago and by biochemical study this G6PD was reported to be a new variant G6PD Bangkok. We, herein, report two families with CNSHA due to G6PD deficiency. In the first family, we have been following up the clinical course of the patient with G6PD Bangkok. In addition to chronic hemolysis, he had three acute hemolytic episodes requiring blood transfusions during childhood period. Multiple gallstones were detected at the age of 27. His two daughters who inherited G6PD Bangkok from him and G6PD Vanua Lava from his wife are asymptomatic. Both of them had NNJ and persistent evidences of compensated hemolysis. Molecular analysis revealed a novel missense mutation 825 G→C predicting 275 Lys→Asn causing G6PD Bangkok. In the second family, two male siblings are affected. They had NNJ and several hemolytic episodes which required blood transfusions. On follow-up they have been diagnosed with chronic hemolysis as evidenced by reticulocytosis and indirect hyperbilirubinemia. Molecular analysis revealed combined missense mutations in exons 12 and 13. The first mutation was 1376 G→T predicting 459 Arg→Leu (known as G6PD Canton) and the second one was 1502 T→G predicting 501 Phe→Cys. We designated the resulting novel G6PD variant, G6PD Bangkok Noi.

  1. Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination.

    PubMed

    Tabatabaei, Seyed Mehdi; Salimi Khorashad, Alireza; Sakeni, Mohammad; Raeisi, Ahmad; Metanat, Zahra

    2015-03-15

    Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked genetic disorder with a relatively high frequency in malaria-endemic regions. It is an obstacle to malaria elimination, as primaquine administered in the treatment of malaria can cause hemolysis in G6PD-deficient individuals. This study presents information on the prevalence of G6PD deficiency in Sistan and Balouchetsan province, which hosts more than 90% of Plasmodium vivax malaria cases in Iran. This type of information is needed for a successful malaria elimination program. A total of 526 students were randomly recruited through schools located in southeast Iran. Information was collected by interviewing the students using a structured questionnaire. Blood samples taken on filter papers were examined for G6PD deficiency using the fluorescent spot test. Overall, 72.8% (383/526) of the subjects showed normal G6PD enzyme function. Mild and severe G6PD deficiency was observed in 14.8% (78) and 12.2% (64) of subjects, respectively. A total 193/261 males (73.9%) and 190/265 (72%) females had normal enzyme activity. Mild G6PD deficiency was observed in 10.8% (28) and 18.9% (50) of male and female subjects, respectively. However, in comparison with females, a greater proportion of males showed severe enzyme deficiency (15.3% versus 9.1%). All these differences were statistically significant (p < 0.006). G6PD deficiency is highly prevalent in southeast Iran. G6PD-deficient individuals are susceptible to potentially severe and life-threatening hemolytic reactions after primaquine treatment. In order to achieve malaria elimination goals in the province, G6PD testing needs to be made routinely available within the health system.

  2. Safety of 8-aminoquinolines given to people with G6PD deficiency: protocol for systematic review of prospective studies.

    PubMed

    Uthman, Olalekan A; Saunders, Rachel; Sinclair, David; Graves, Patricia; Gelband, Hellen; Clarke, Aileen; Garner, Paul

    2014-05-14

    A single dose or short course of primaquine given to people infected with malaria may reduce transmission of Plasmodium falciparum through its effects on gametocytes. Primaquine is also known to cause haemolysis in people with variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency. The objective of this systematic review was to assess the risk of adverse effects in people with G6PD deficiency given primaquine or other 8-aminoquinoline (8AQ) as a single dose or short course (less than 7 days). We will search the following databases: Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS. Prospective cohort studies, randomised and quasi-randomised trials that evaluated 8AQs for whatever reason in adults or children with a known G6PD deficiency will be included. Two authors will independently assess each study for eligibility, risk of bias and extract data. This systematic review will be published in a peer-reviewed journal. Brief reports of the review findings will be disseminated directly to the appropriate audiences and the WHO Technical Expert Group in Malaria Chemotherapy. As no primary data collection will be undertaken, no additional formal ethical assessment and informed consent are required. The protocol is registered with PROSPERO, registration number CRD42013006518. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Modeling Plasmodium vivax: relapses, treatment, seasonality, and G6PD deficiency.

    PubMed

    Chamchod, Farida; Beier, John C

    2013-01-07

    Plasmodium vivax (P. vivax) is one of the most important human malaria species that is geographically widely endemic and causes social and economic burden globally. However, its consequences have long been neglected and underestimated as it has been mistakenly considered a benign and inconsequential malaria species as compared to Plasmodium falciparum. One of the important differences between P. falciparum and P. vivax is the formation of P. vivax latent-stage parasites (hypnozoites) that can cause relapses after a course of treatment. In this work, mathematical modeling is employed to investigate how patterns of incubation periods and relapses of P. vivax, variation in treatment, and seasonal abundance of mosquitoes influence the number of humans infected with P. vivax and the mean age at infection of humans in tropical and temperate regions. The model predicts that: (i) the number of humans infected with P. vivax may increase when an incubation period of parasites in humans and a latent period of hypnozoites decrease; (ii) without primaquine, the only licensed drug to prevent relapses, P. vivax may be highly prevalent; (iii) the mean age at infection of humans may increase when a latent period of hypnozoites increases; (iv) the number of infectious humans may peak at a few months before the middle of each dry season and the number of hypnozoite carriers may peak at nearly the middle of each dry season. In addition, glucose-6-phosphate-dehydrogenase (G6PD) deficiency, which is the most common enzyme defect in humans that may provide some protection against P. vivax infection and severity, is taken into account to study its impact on the number of humans infected with P. vivax. Modeling results indicate that the increased number of infected humans may result from a combination of a larger proportion of humans with G6PD deficiency in the population, a lesser protection of G6PD deficiency to P. vivax infection, and a shorter latent period of hypnozoites.

  4. Comparison of serum copper, magnesium, zinc and calcium levels between G6PD deficient and normal Chinese adults.

    PubMed

    Chen, B H; Tsai, J L; Tsai, L Y; Chao, M C

    1999-11-01

    Minerals are important for normal hematopoiesis and may play a role in acute hemolytic anemia induced by G6PD deficiency. To compare serum magnesium, copper, zinc and calcium levels between G6PD deficiency and normal control adults, we investigated 69 G6PD deficient (28 male, 41 female) and 61 age- matched G6PD normal adults (26 male, 35 female). Serum magnesium, copper, zinc and calcium levels were determined by atomic absorbance spectrometry. Our results revealed that male adults with G6PD deficiency had significantly higher serum copper and magnesium levels than those of the control group (P < 0.01, < 0.05, respectively). In G6PD normal adults, serum copper levels were significantly lower in males than in females (P < 0.01). In the group of G6PD deficiency adults, serum copper levels in males (103.0 +/- 10.4 ug/dL) were significantly lower than those in females (139.0 +/- 34.3 ug/dL) (P < 0.01). Serum magnesium values and zinc values in males (2.42 +/- 0.38 mEq/L and 102.2 +/- 26.5 ug/dL) were significantly higher than those in females (2.07 +/- 0.20 mEq/L and 87.0 +/- 14.9 ug/dL) (P all < 0.01). Female adults with G6PD deficiency had significantly higher serum calcium levels and lower magnesium levels than those of the control group (P all < 0.01). The significantly higher levels of serum copper and magnesium in G6PD deficient male adults may play some role concerning red blood cells in resistance to plasmodium falciparum.

  5. Precautionary Measures for Successful Open Heart Surgery in G6PD Deficient Patient- A Case Report.

    PubMed

    Kumar, Rupesh

    2016-12-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is among the most common enzymatic disorders of red blood cells. Cardiac surgeries on this group of individuals are associated with an additional risk in terms of impaired oxygenation, prolonged ventilation and increased risk of haemolysis. These patients have a very low threshold for haemolysis due to oxidative stress. Many commonly used drugs also predispose the individual for haemolysis when they are subjected to surgery. Here we present a known case of G6PD deficient patient with symptoms of breathlessness for the last nine years who was taken for surgery with pre-planned precautionary measures to avoid unnecessary haemolysis. The echocardiography report revealed severe mixed mitral lesion and moderate tricuspid regurgitation. On general examination she had mild pallor and icterus. We planned for a thorough investigation to prepare her for mitral valve replacement and tricuspid annuloplasty. These groups of patients are at high risk of haemolysis during perioperative period and need prolonged mechanical ventilation and hospital stay due to impaired oxygen carrying capacity and oxidative stress due to deficient free radical scavenging system. The patient underwent mechanical mitral valve replacement and tricuspid annuloplasty under cardiopulmonary bypass with precautionary measures to prevent the risk of haemolysis and associated complications. She had an uneventful recovery.

  6. Precautionary Measures for Successful Open Heart Surgery in G6PD Deficient Patient- A Case Report

    PubMed Central

    2016-01-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is among the most common enzymatic disorders of red blood cells. Cardiac surgeries on this group of individuals are associated with an additional risk in terms of impaired oxygenation, prolonged ventilation and increased risk of haemolysis. These patients have a very low threshold for haemolysis due to oxidative stress. Many commonly used drugs also predispose the individual for haemolysis when they are subjected to surgery. Here we present a known case of G6PD deficient patient with symptoms of breathlessness for the last nine years who was taken for surgery with pre-planned precautionary measures to avoid unnecessary haemolysis. The echocardiography report revealed severe mixed mitral lesion and moderate tricuspid regurgitation. On general examination she had mild pallor and icterus. We planned for a thorough investigation to prepare her for mitral valve replacement and tricuspid annuloplasty. These groups of patients are at high risk of haemolysis during perioperative period and need prolonged mechanical ventilation and hospital stay due to impaired oxygen carrying capacity and oxidative stress due to deficient free radical scavenging system. The patient underwent mechanical mitral valve replacement and tricuspid annuloplasty under cardiopulmonary bypass with precautionary measures to prevent the risk of haemolysis and associated complications. She had an uneventful recovery. PMID:28208930

  7. Practical approach for characterization of glucose 6-phosphate dehydrogenase (G6PD) deficiency in countries with population ethnically heterogeneous: description of seven new G6PD mutants.

    PubMed

    Moradkhani, Kamran; Mekki, Chadia; Bahuau, Michel; Te, Valerie Li Thiao; Holder, Muriel; Pissard, Serge; Préhu, Claude; Rose, Christian; Wajcman, Henri; Galactéros, Frédéric

    2012-02-01

    We present a rapid strategy based on Restriction Fragment Length Polymorphism (RFLP) analysis to characterize the more frequent glucose 6-phosphate dehydrogenase (G6PD) variants observed in a population with high gene flow. During a study involving more than 600 patients, we observed mainly G6PD A(-) (c.202G>A, c.376A>G; p.Val68Met, p.Asn126Asp), G6PD Mediterranean (Med) (c.563C>T, p.Ser188Phe), and G6PD Betica (c.376A>G, 542A>T; p.126Asn>Asp, 181Asp>Val) with addition of a few rare ones. A number of 10 abnormalities amounted to 92% of all the molecular defects. In addition, seven new mutations were found: three presented with acute hemolytic anemia following oxidative stress [G6PD Nice (c.1380G>C, p.Glu460Asp), G6PD Roubaix (c.811G>C, p.Val271Leu), and G6PD Toledo (c.496C>T, p.Arg166Cys)], three with different degrees of chronic hemolytic anemia [G6PD Lille (c.821A>T, p.Glu274Val), G6PD Villeurbanne (c.1000_1002delACC, p.Thr334del), and G6PD Amiens (c.1367A>T, p.Asp456Val)] and one found fortuitously G6PD Montpellier (c.1132G>A, p.Gly378Ser).

  8. Effects of environmental oxidant stressors on individuals with a G-6-PD deficiency with particular reference to an animal model.

    PubMed Central

    Calabrese, E J; Moore, G; Brown, R

    1979-01-01

    Individuals with a G-6-PD deficiency have long been known to be at increased risk to experience acute hemolysis following exposure to elevated levels of certain oxidant drugs and industrial chemicals. However, the recognition of enhanced susceptibility to environmental (or ambient) pollutants has generally not been considered. Recent theoretical studies have suggested that elevated levels of ambient ozone may be an etiologic factor in the onset of acute hemolysis in the G-6-PD deficient individual. Furthermore, the proposed usage of either chloramines or chlorine dioxide as replacements for chlorine for the disinfection of drinking water should be investigated with respect to their potential adverse effects of individuals at increased risk to oxidant stressors. In order to test these theoretical associations, two mouse strains, one with low and the other with high levels of G-6-PD activity in their red blood cells are being investigated to determine if they simulate human G-6-PD deficient and normal individuals, respectively. Preliminary results indicate that the mouse strain with low G-6-PD activity is markedly more susceptible to sodium chlorite than mice of the high G-6-PD strain. This differential susceptibility to sodium chlorite toxicity between the high and low G-6-PD mouse strains suggests that further research designed to validate the efficacy of this mouse model as a predictor of the human situation is warranted. PMID:510241

  9. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia

    PubMed Central

    Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy ME; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris CA; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations. DOI: http://dx.doi.org/10.7554/eLife.15085.001 PMID:28067620

  10. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype.

    PubMed

    Relling, M V; McDonagh, E M; Chang, T; Caudle, K E; McLeod, H L; Haidar, C E; Klein, T; Luzzatto, L

    2014-08-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia (AHA) induced by a number of drugs. We provide guidance as to which G6PD genotypes are associated with G6PD deficiency in males and females. Rasburicase is contraindicated in G6PD-deficient patients due to the risk of AHA and possibly methemoglobinemia. Unless preemptive genotyping has established a positive diagnosis of G6PD deficiency, quantitative enzyme assay remains the mainstay of screening prior to rasburicase use. The purpose of this article is to help interpret the results of clinical G6PD genotype tests so that they can guide the use of rasburicase. Detailed guidelines on other aspects of the use of rasburicase, including analyses of cost-effectiveness, are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on https://www.pharmgkb.org/page/cpic to reflect new developments in the field.

  11. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

    PubMed

    Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy Me; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris Ca; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

    2017-01-09

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

  12. Tools for mass screening of G6PD deficiency: validation of the WST8/1-methoxy-PMS enzymatic assay in Uganda.

    PubMed

    De Niz, Mariana; Eziefula, Alice C; Othieno, Lucas; Mbabazi, Edith; Nabukeera, Damalie; Ssemmondo, Emmanuel; Gonahasa, Samuel; Tumwebaze, Patrick; Diliberto, Deborah; Maiteki-Sebuguzi, Catherine; Staedke, Sarah G; Drakeley, Chris

    2013-06-19

    The distribution of the enzymopathy glucose-6-phosphate dehydrogenase (G6PD) deficiency is linked to areas of high malaria endemicity due to its association with protection from disease. G6PD deficiency is also identified as the cause of severe haemolysis following administration of the anti-malarial drug primaquine and further use of this drug will likely require identification of G6PD deficiency on a population level. Current conventional methods for G6PD screening have various disadvantages for field use. The WST8/1-methoxy PMS method, recently adapted for field use, was validated using a gold standard enzymatic assay (R&D Diagnostics Ltd ®) in a study involving 235 children under five years of age, who were recruited by random selection from a cohort study in Tororo, Uganda. Blood spots were collected by finger-prick onto filter paper at routine visits, and G6PD activity was determined by both tests. Performance of the WST8/1-methoxy PMS test under various temperature, light, and storage conditions was evaluated. The WST8/1-methoxy PMS assay was found to have 72% sensitivity and 98% specificity when compared to the commercial enzymatic assay and the AUC was 0.904, suggesting good agreement. Misclassifications were at borderline values of G6PD activity between mild and normal levels, or related to outlier haemoglobin values (<8.0 gHb/dl or >14 gHb/dl) associated with ongoing anaemia or recent haemolytic crises. Although severe G6PD deficiency was not found in the area, the test enabled identification of low G6PD activity. The assay was found to be highly robust for field use; showing less light sensitivity, good performance over a wide temperature range, and good capacity for medium-to-long term storage. The WST8/1-methoxy PMS assay was comparable to the currently used standard enzymatic test, and offers advantages in terms of cost, storage, portability and use in resource-limited settings. Such features make this test a potential key tool for deployment in the

  13. Heterogeneous alleles comprising G6PD deficiency trait in West Africa exert contrasting effects on two major clinical presentations of severe malaria.

    PubMed

    Shah, Shivang S; Rockett, Kirk A; Jallow, Muminatou; Sisay-Joof, Fatou; Bojang, Kalifa A; Pinder, Margaret; Jeffreys, Anna; Craik, Rachel; Hubbart, Christina; Wellems, Thomas E; Kwiatkowski, Dominic P

    2016-01-07

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency exhibits considerable allelic heterogeneity which manifests with variable biochemical and clinical penetrance. It has long been thought that G6PD deficiency confers partial protection against severe malaria, however prior genetic association studies have disagreed with regard to the strength and specificity of a protective effect, which might reflect differences in the host genetic background, environmental influences, or in the specific clinical phenotypes considered. A case-control association study of severe malaria was conducted in The Gambia, a region in West Africa where there is considerable allelic heterogeneity underlying expression of G6PD deficiency trait, evaluating the three major nonsynonymous polymorphisms known to be associated with enzyme deficiency (A968G, T542A, and C202T) in a cohort of 3836 controls and 2379 severe malaria cases. Each deficiency allele exhibited a similar trend toward protection against severe malaria overall (15-26% reduced risk); however, in stratifying severe malaria to two of its constituent clinical subphenotypes, severe malarial anaemia (SMA) and cerebral malaria (CM), the three deficiency alleles exhibited trends of opposing effect, with risk conferred to SMA and protection with respect to CM. To assess the overall effect of G6PD deficiency trait, deficiency alleles found across all three loci were pooled. G6PD deficiency trait was found to be significantly associated with protection from severe malaria overall (OR 0.83 [0.75-0.92], P = 0.0006), but this was limited to CM (OR 0.73 [0.61-0.87], P = 0.0005), with a trend toward increased risk for SMA, especially in fully-deficient individuals (OR 1.43 [0.99-2.08], P = 0.056). Sex-stratified testing largely comported with these results, with evidence suggesting that protection by G6PD deficiency trait is conferred to both males and females, though susceptibility to SMA may be restricted to fully-deficient male hemizygotes

  14. A Novel de novo Mutation in the G6PD Gene in a Korean Boy with Glucose-6-phosphate Dehydrogenase Deficiency: Case Report.

    PubMed

    Jang, Mi-Ae; Kim, Ji-Yoon; Lee, Ki-O; Kim, Sun-Hee; Koo, Hong Hoe; Kim, Hee-Jin

    2015-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by a mutation in the G6PD gene on Xq28. Herein, we describe a Korean boy with G6PD deficiency resulting from a novel mutation in G6PD. A 20-month-old boy with hemolytic anemia was referred for molecular diagnosis. He had no relevant family history. The G6PD activity was severely decreased at 0.2 U/g Hb (severe deficiency). Direct sequencing analyses on the G6PD gene revealed that he was hemizygous for a novel missense variant, c.1187C>G (p.Pro396Arg), in exon 10 of G6PD. Family study involving his parents revealed the de novo occurrence of the mutation. This is the first report of genetically confirmed G6PD deficiency in Korea.

  15. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in Greek newborns: the Mediterranean C563T mutation screening.

    PubMed

    Molou, Elina; Schulpis, Kleopatra H; Thodi, Georgia; Georgiou, Vassiliki; Dotsikas, Yannis; Papadopoulos, Konstantinos; Biti, Sofia; Loukas, Yannis L

    2014-04-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) gene is located at the X-chromosome at Xq28 and the disease is recessively inherited predominantly in males. More than 400 variants have been proposed based on clinical and enzymatic studies. The aim of the current study was to identify C563T mutation in G6PD-deficient newborns and to correlate the enzyme residual activity with the presence of the mutation. Some 1189 full-term neonates aged 3-5 days old were tested for G6PD activity in dried blood spots from Guthrie cards using a commercial kit. DNA extraction from Guthrie cards and mutation identification among the deficient samples were performed with current techniques. A total of 92 (7.7%) newborns were G6PD-deficient. In 46 (50%), the mutation C563T was identified. The residual activity in C563T hemizygote males (n = 28) was statistically significantly lower (1.23 ± 0.93 U/g Hb) than that in non-C563T G6PD-deficient males (n = 25) (4.01 ± 1.20 U/g Hb, p < 0.0001) and in controls (13.6 ± 2.9 U/g Hb, p < 0.0001). In C563T heterozygote females, the estimated enzyme activity was lower than that determined in non-C563T females. Male C563T hemizygotes suffer from G6PD deficiency and severe neonatal jaundice. G6PD activity showed statistically significant correlation with total bilirubin blood levels.

  16. Large Cohort Screening of G6PD Deficiency and the Mutational Spectrum in the Dongguan District in Southern China

    PubMed Central

    Ma, Keze; Li, Wenrui; Ma, Qiang; He, Xiaoguang; He, Yuejing; He, Ting; Lu, Xiaomei

    2015-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzymatic disorder of the erythrocytes that affects 400 million people worldwide. We developed a PCR-reverse dot blot (RDB) assay to screen twenty genotypes of seventeen Chinese G6PD mutations and investigate the spectrum of G6PD deficiency mutations in Dongguan District, Guangdong Province, in southern China. Method The PCR-RDB assay consists of multiplex PCR amplification of seven fragments in the G6PD target sequence of wild-type and mutant genomic DNA samples followed by hybridization to a test strip containing allele-specific oligonucleotide probes. A total of 16,464 individuals were analyzed by a combination of phenotypic screening and genotypic detection using the PCR-RDB assay and DNA sequence analysis. Results The PCR-RDB assay had a detection rate of 98.1%, which was validated by direct sequencing in a blind study with 100% concordance. The G6PD deficiency incidence rate in Dongguan District is 4.08%. Thirty-two genotypes from 469 individuals were found. The two most common variants were c.1376G>T and c.1388G>A, followed by c.95A>G, c.871G>A, c.392G>T, and c.1024 C>T. In addition, two rare mutations (c.703C>A and c.406C>T) were detected by DNA sequencing analysis. In our study, 65 cases harbored the C1311T/IVS polymorphism and 67 cases were homozygote. Conclusion The PCR-RDB assay we established is a reliable and effective method for screening G6PD mutations in the Chinese population. Data on the spectrum of mutations in the Dongguan District is beneficial to the clinical diagnosis and prevention of G6PD deficiency. PMID:25775246

  17. A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency.

    PubMed

    Boonyuen, Usa; Chamchoy, Kamonwan; Swangsri, Thitiluck; Junkree, Thanyaphorn; Day, Nicholas P J; White, Nicholas J; Imwong, Mallika

    2017-11-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common polymorphism and enzymopathy in humans, affecting approximately 400 million people worldwide. It is responsible for various clinical manifestations, including favism, hemolytic anemia, chronic non-spherocytic hemolytic anemia, spontaneous abortion, and neonatal hyperbilirubinemia. Understanding the molecular mechanisms underlying the severity of G6PD deficiency is of great importance but that of many G6PD variants are still unknown. In this study, we report the construction, expression, purification, and biochemical characterization in terms of kinetic properties and stability of five clinical G6PD variants-G6PD Bangkok, G6PD Bangkok noi, G6PD Songklanagarind, G6PD Canton+Bangkok noi, and G6PD Union+Viangchan. G6PD Bangkok and G6PD Canton+Bangkok noi showed a complete loss of catalytic activity and moderate reduction in thermal stability when compared with the native G6PD. G6PD Bangkok noi and G6PD Union+Viangchan showed a significant reduction in catalytic efficiency, whereas G6PD Songklanagarind showed a catalytic activity comparable to the wild-type enzyme. The Union+Viangchan mutation showed a remarkable effect on the global stability of the enzyme. In addition, our results indicate that the location of mutations in G6PD variants affects their catalytic activity, stability, and structure. Hence, our results provide a molecular explanation for clinical manifestations observed in individuals with G6PD deficiency. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Screening for G6PD Deficiency Among Neonates with Neonatal Jaundice Admitted to Tertiary Care Center: A Need in Disguise.

    PubMed

    Kumar, Kishwer; Sohaila, Arjumand; Tikmani, Shiyam Sunder; Khan, Iqtidar Ahmed; Zafar, Anila

    2015-08-01

    This study was conducted to determine the association of Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency among neonates admitted with jaundice at the neonatal intensive care unit, well baby nursery and neonatal step down nursery of the Aga Khan University Hospital, Karachi, Pakistan, from January to June 2010. A total of 205 neonates following the selection criteria were included. All selected neonates have their venous blood drawn, saved in EDTA bottle and sent to laboratory of The Aga Khan University Hospital (AKUH). The laboratory results of whether G-6-PD deficiency was present or not was recorded in the proforma. G-6-PD was deficient in 19 neonates (9.3%). All neonates were male.

  19. G6PD deficiency in Latin America: systematic review on prevalence and variants

    PubMed Central

    Monteiro, Wuelton M; Val, Fernando FA; Siqueira, André M; Franca, Gabriel P; Sampaio, Vanderson S; Melo, Gisely C; Almeida, Anne CG; Brito, Marcelo AM; Peixoto, Henry M; Fuller, Douglas; Bassat, Quique; Romero, Gustavo AS; Maria Regina F, Oliveira; Marcus Vinícius G, Lacerda

    2014-01-01

    Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available. PMID:25141282

  20. G6PD deficiency in Latin America: systematic review on prevalence and variants.

    PubMed

    Monteiro, Wuelton M; Val, Fernando F A; Siqueira, André M; Franca, Gabriel P; Sampaio, Vanderson S; Melo, Gisely C; Almeida, Anne C G; Brito, Marcelo A M; Peixoto, Henry M; Fuller, Douglas; Bassat, Quique; Romero, Gustavo A S; Maria Regina F, Oliveira; Marcus Vinícius G, Lacerda

    2014-08-01

    Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.

  1. X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe Malaria

    PubMed Central

    Doumbo, Ogobara K; Wellems, Thomas E; Diallo, Dapa A

    2007-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A− form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. Methods and Findings We conducted large case-control studies of the A− form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies. Conclusions The A− form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is

  2. Heterogeneity of G6PD deficiency prevalence in Mozambique: a school-based cross-sectional survey in three different regions.

    PubMed

    Galatas, Beatriz; Mabote, Lurdes; Simone, Wilson; Matambisso, Gloria; Nhamussua, Lidia; Mañú-Pereira, María Del Mar; Menéndez, Clara; Saute, Francisco; Macete, Eusebio; Bassat, Quique; Alonso, Pedro; Aide, Pedro

    2017-01-19

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary enzymatic abnormality that affects more than 400 million people worldwide. Most deficient individuals do not manifest any symptoms; however, several precipitant agents-such as fava intake, infections, or several drugs-may trigger acute haemolytic anaemia. Countries should be informed of the prevalence of this enzymatic anomaly within their borders, in order to make safe and appropriate national decisions regarding the use of potentially unsafe drugs for G6PD deficient individuals. A school-based cross-sectional survey was conducted in three districts in Mozambique, namely Manhiça, located in the south; Mocuba in the centre; and Pemba in the northern tip of the country. G6PD deficiency was evaluated using the CareStart™ diagnostic test, and enzyme activity levels were measured through fluorescence spectrophotometry in deficient individuals. Chi squared and ANOVA tests were used to assess prevalence and mean enzyme activity differences, and logistic regression was used to identify risk factors associated to the deficiency. G6PD deficiency prevalence estimates were lowest in the northern city of Pemba (8.3%) and among Emakhuwas and Shimakondes, and higher in the centre and southern regions of the country (16.8 and 14.6%, respectively), particularly among Elomwes and Xichanganas. G6PD deficiency was significantly more prevalent among male students than females (OR = 1.4, 95% CI 1.0-1.8, p = 0.02), although enzyme activity levels were not different among deficient individuals from either gender group. Finally, median deficiency levels were found to be more severe among the deficient students from the north (0.7 U/gHg [0.2-0.7] p < 0.001) and south (0.7 U/gHg [0.5-2.5]), compared to those from the centre (1.4 U/gHg [0.6-2.1]). These findings suggest that Mozambique, as a historically high malaria-endemic country has considerable levels of G6PD deficiency, that vary significantly

  3. Comparative Study of Antimalarial and Other Drugs on G6PD Deficient Red Cells.

    DTIC Science & Technology

    the WR compounds previously studied. The suggested use of xylitol as a protective agent against hemolytic drugs (Wang et al) had raised considerable...expectation. Unfortunately, xylitol at the dosages of 20 and 30 g./day was unable, in our experimental set up (transfusion of 51 Cr tagged G6PD

  4. Evaluation of the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT) in a malaria endemic area in Ghana, Africa.

    PubMed

    Adu-Gyasi, Dennis; Asante, Kwaku Poku; Newton, Sam; Dosoo, David; Amoako, Sabastina; Adjei, George; Amoako, Nicholas; Ankrah, Love; Tchum, Samuel Kofi; Mahama, Emmanuel; Agyemang, Veronica; Kayan, Kingsley; Owusu-Agyei, Seth

    2015-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most widespread enzyme defect that can result in red cell breakdown under oxidative stress when exposed to certain medicines including antimalarials. We evaluated the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT) as a point-of-care tool for screening G6PD deficiency. A cross-sectional study was conducted among 206 randomly selected and consented participants from a group with known G6PD deficiency status between February 2013 and June 2013. A maximum of 1.6ml of capillary blood samples were used for G6PD deficiency screening using CareStart G6PD RDT and Trinity qualitative with Trinity quantitative methods as the "gold standard". Samples were also screened for the presence of malaria parasites. Data entry and analysis were done using Microsoft Access 2010 and Stata Software version 12. Kintampo Health Research Centre Institutional Ethics Committee granted ethical approval. The sensitivity (SE) and specificity (SP) of CareStart G6PD deficiency RDT was 100% and 72.1% compared to Trinity quantitative method respectively and was 98.9% and 96.2% compared to Trinity qualitative method. Malaria infection status had no significant (P=0.199) change on the performance of the G6PD RDT test kit compared to the "gold standard". The outcome of this study suggests that the diagnostic performance of the CareStart G6PD deficiency RDT kit was high and it is acceptable at determining the G6PD deficiency status in a high malaria endemic area in Ghana. The RDT kit presents as an attractive tool for point-of-care G6PD deficiency for rapid testing in areas with high temperatures and less expertise. The CareStart G6PD deficiency RDT kit could be used to screen malaria patients before administration of the fixed dose primaquine with artemisinin-based combination therapy.

  5. Field trials of a rapid test for G6PD deficiency in combination with a rapid diagnosis of malaria.

    PubMed

    Tantular, I S; Iwai, K; Lin, K; Basuki, S; Horie, T; Htay, H H; Matsuoka, H; Marwoto, H; Wongsrichanalai, C; Dachlan, Y P; Kojima, S; Ishii, A; Kawamoto, F

    1999-04-01

    A rapid single-step screening method for detection of glucose-6-phosphate dehydrogenase (G6 PD) deficiency was evaluated on Halmahera Island, Maluku Province, Indonesia, and in Shan and Mon States, Myanmar, in combination with a rapid diagnosis of malaria by an acridine orange staining method. Severe deficiency was detected by the rapid test in 45 of 1126 volunteers in Indonesia and 54 of 1079 in Myanmar, but it was difficult to distinguish blood samples with mild deficiency from those with normal activity. 89 of 99 severely deficient cases were later confirmed by formazan ring method in the laboratory, but 5 with mild and 5 with no deficiency were misdiagnosed as severe. Of the samples diagnosed as mild and no deficiency on-site, none was found to be severely deficient by the formazan method. Malaria patients were simultaenously++ detected on-site in 273 samples on Halmahera island and 277 samples from Shan and Mon States. In Mon State, primaquine was prescribed safely to G6 PD-normal malaria patients infected with Plasmodium vivax and/or gametocytes of P. falciparum. The new rapid test for G6 PD deficiency may be useful for detecting severe cases under field conditions, and both rapid tests combined are can be useful in malaria-endemic areas, facilitating early diagnosis, prompt and radical treatment of malaria and suppression of malaria transmission.

  6. Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Ouest and Sud-Est departments of Haiti.

    PubMed

    von Fricken, Michael E; Weppelmann, Thomas A; Eaton, Will T; Alam, Meer T; Carter, Tamar E; Schick, Laura; Masse, Roseline; Romain, Jean R; Okech, Bernard A

    2014-07-01

    Malaria remains a significant public health issue in Haiti, with chloroquine (CQ) used almost exclusively for the treatment of uncomplicated infections. Recently, single dose primaquine (PQ) was added to the Haitian national malaria treatment policy, despite a lack of information on the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency within the population. G6PD deficient individuals who take PQ are at risk of developing drug induced hemolysis (DIH). In this first study to examine G6PD deficiency rates in Haiti, 22.8% (range 14.9%-24.7%) of participants were found to be G6PD deficient (class I, II, or III) with 2.0% (16/800) of participants having severe deficiency (class I and II). Differences in deficiency were observed by gender, with males having a much higher prevalence of severe deficiency (4.3% vs. 0.4%) compared to females. Male participants were 1.6 times more likely to be classified as deficient and 10.6 times more likely to be classified as severely deficient compared to females, as expected. Finally, 10.6% (85/800) of the participants were considered to be at risk for DIH. Males also had much higher rates than females (19.3% vs. 4.6%) with 4.9 times greater likelihood (p value 0.000) of having an activity level that could lead to DIH. These findings provide useful information to policymakers and clinicians who are responsible for the implementation of PQ to control and manage malaria in Haiti. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency.

    PubMed

    Sirdah, Mahmoud M; Shubair, Mohammad E; Al-Kahlout, Mustafa S; Al-Tayeb, Jamal M; Prchal, Josef T; Reading, N Scott

    2017-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficient children, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.

  8. [Hemolytic anemia after voluntary ingestion of henna (Lawsonia inermis) decoction by a young girl with G6PD deficiency].

    PubMed

    Perinet, I; Lioson, E; Tichadou, L; Glaizal, M; de Haro, L

    2011-06-01

    Henna (Lawsonia inermis) is a shrub bearing leaves that are crushed and used for cosmetic purposes in Asia and Africa. In several countries, henna decoction is ingested as a traditional drug to induce abortion. One component of Henna, known as Lawsone, can induce hemolysis in G6PD-deficient patients after cutaneous exposure or ingestion. The purpose of this report is to describe a case of severe hemolytic anemia after voluntary ingestion of Henna decoction to induce abortion. This complication led to diagnosis of partial moderate G6PD-deficiency in the 17-year-old patient living in Mayotte in the Indian Ocean. This report emphasizes the life-threatening hazards associated with some plant extracts used as traditional medicines.

  9. High prevalence of hemoglobin disorders and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Republic of Guinea (West Africa).

    PubMed

    Millimono, Tamba S; Loua, Kovana M; Rath, Silvia L; Relvas, Luis; Bento, Celeste; Diakite, Mandiou; Jarvis, Martin; Daries, Nathalie; Ribeiro, Leticia M; Manco, Licínio; Kaeda, Jaspal S

    2012-01-01

    Reliable and accurate epidemiological data is a prerequisite for a cost effective screening program for inherited disorders, which however, is lacking in a number of developing countries. Here we report the first detailed population study in the Republic of Guinea, a sub-Saharan West African country, designed to assess the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobinopathies, including screening for thalassemia. Peripheral blood samples from 187 Guinean adults were screened for hemoglobin (Hb) variants by standard hematological methods. One hundred and ten samples from males were screened for G6PD deficiency by the fluorescent spot test. Molecular analysis was performed for the most common α-thalassemia (α-thal) deletions, β-globin gene mutations, G6PD variants B (376A), A (376G), A- (376G/202A) and Betica (376G/968C), using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) or sequencing. Of the 187 subjects screened, 36 were heterozygous for Hb S [β6(A3)Glu→Val, GAG>GTG] (allele frequency 9.62%). Sixty-four subjects were heterozygous and seven were homozygous for the -α(3.7) kb deletion (allele frequency 20.85%). β-Thalassemia alleles were detected in five subjects, four with the -29 (A>G) mutation (allele frequency 1.07%) and one with codon 15 (TGG>TAG) (allele frequency 0.96%). The G6PD A- and G6PD Betica deficient variants were highly prevalent with a frequency of 5.7 and 3.3%, respectively. While we did not test for ferritin levels or α(0)-thal, four females (5.2%) had red cell indices strongly suggestive of iron deficient anemia: Hb <9.7 g/dL; MCH <19.3 pg; MCV <68.2; MCHC <31.6 g/dl; RDW >19.8%. Our results are consistent with high frequency of alleles such as Hb S, α-thal and G6PD deficient alleles associated with malaria resistance. Finding a 9.6% Hb S allele frequency supports the notion for a proficient neonatal screening to identify the sickle cell patients, who might benefit

  10. DNA damage and apoptosis in mononuclear cells from glucose-6-phosphate dehydrogenase-deficient patients (G6PD Aachen variant) after UV irradiation.

    PubMed

    Efferth, T; Fabry, U; Osieka, R

    2001-03-01

    Patients affected with X chromosome-linked, hereditary glucose-6-phosphate dehydrogenase (G6PD) deficiency suffer from life-threatening hemolytic crises after intake of certain drugs or foods. G6PD deficiency is associated with low levels of reduced glutathione. We analyzed mononuclear white blood cells (MNC) of three males suffering from the German G6PD Aachen variant, four heterozygote females of this family, one G6PD-deficient male from another family coming from Iran, and six healthy male volunteers with respect to their DNA damage in two different genes (G6PD and T-cell receptor-delta) and their propensity to enter apoptosis after UV illumination (0.08-5.28 J/cm2). As determined by PCR stop assays, there was more UV-induced DNA damage in MNC of G6PD-deficient male patients than in those of healthy subjects. MNC of G6PD-deficient patients showed a higher rate of apoptosis after UV irradiation than MNC of healthy donors. MNC of heterozygote females showed intermediate rates of DNA damage and apoptosis. It is concluded that increased DNA damage may be a result of deficient detoxification of reactive oxygen species by glutathione and may ultimately account for the higher rate of apoptosis in G6PD-deficient MNC.

  11. First evaluation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in vivax malaria endemic regions in the Republic of Korea.

    PubMed

    Goo, Youn-Kyoung; Ji, So-Young; Shin, Hyun-Il; Moon, Jun-Hye; Cho, Shin-Hyung; Lee, Won-Ja; Kim, Jung-Yeon

    2014-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect and affects more than 400 million people worldwide. This deficiency is believed to protect against malaria because its global distribution is similar. However, this genetic disorder may be associated with potential hemolytic anemia after treatment with anti-malarials, primaquine or other 8-aminoquinolines. Although primaquine is used for malaria prevention, no study has previously investigated the prevalence of G6PD variants and G6PD deficiency in the Republic of Korea (ROK). Two commercialized test kits (Trinity G-6-PDH and CareStart G6PD test) were used for G6PD deficiency screening. The seven common G6PD variants were investigated by DiaPlexC kit in blood samples obtained living in vivax malaria endemic regions in the ROK. Of 1,044 blood samples tested using the CareStart G6PD test, none were positive for G6PD deficiency. However, a slightly elevated level of G6PD activity was observed in 14 of 1,031 samples tested with the Trinity G-6-PDH test. Forty-nine of the 298 samples with non-specific amplification by DiaPlexC kit were confirmed by sequencing to be negative for the G6PD variants. No G6PD deficiency was observed using phenotypic- or genetic-based tests in individuals residing in vivax malaria endemic regions in the ROK. Because massive chemoprophylaxis using primaquine has been performed in the ROK military to kill hypnozoites responsible for relapse and latent stage vivax malaria, further regular monitoring is essential for the safe administration of primaquine.

  12. Origins and implications of neglect of G6PD deficiency and primaquine toxicity in Plasmodium vivax malaria

    PubMed Central

    Baird, Kevin

    2015-01-01

    Most of the tens of millions of clinical attacks caused by Plasmodium vivax each year likely originate from dormant liver forms called hypnozoites. We do not systematically attack that reservoir because the only drug available, primaquine, is poorly suited to doing so. Primaquine was licenced for anti-relapse therapy in 1952 and became available despite threatening patients having an inborn deficiency of glucose-6-phosphate dehydrogenase (G6PD) with acute haemolytic anaemia. The standard method for screening G6PD deficiency, the fluorescent spot test, has proved impractical where most malaria patients live. The blind administration of daily primaquine is dangerous, but so too are the relapses invited by withholding treatment. Absent G6PD screening, providers must choose between risking harm by the parasite or its treatment. How did this dilemma escape redress in science, clinical medicine and public health? This review offers critical historic reflection on the neglect of this serious problem in the chemotherapy of P. vivax. PMID:25943156

  13. An evaluation of concurrent G6PD (A−) deficiency and sickle cell trait in Malian populations of children with severe or uncomplicated P. falciparum malaria

    PubMed Central

    Guindo, Aldiouma; Traore, Karim; Diakite, Seidina; Wellems, Thomas E.; Doumbo, Ogobara K.; Diallo, Dapa Aly

    2016-01-01

    Sickle cell trait (SCT) and glucose-6-phosphate dehydrogenase (G6PD (A−)) deficiency are two common genetic conditions in sub-Saharan Africa. In Mali, SCT and G6PD (A−) deficiency are found at overall frequencies of 12% and 14%, respectively. While SCT and G6PD (A−) deficiency were associated with protection against severe malaria, we have examined the occurrence of the G6PD (A−) polymorphism and SCT together in Malian populations of children with severe or uncomplicated P. falciparum malaria. No evidence for increased protection was detected in children who carried both SCT and the G6PD (A−) polymorphism. A suggestion of greater susceptibility was instead observed for the heterozygous G6PD (A−) versus G6PD normal condition in SCT females (OR 15, P = 0.003). While in addition, larger studies will be needed to further evaluate the possibility of interference between the protective effects of the SCT and G6PD (A−) conditions, we note that these results are reminiscent of the negative epistasis reported for the malaria-protective effects of α+-thalassemia and SCT. Better understanding of the conflicts among malaria-protective polymorphisms may shed light on their observed epidemiological distributions and improve our knowledge of the mechanisms by which they operate. PMID:21786288

  14. Serum lipoprotein pattern as modified in G6PD-deficient children during haemolytic anaemia induced by fava bean ingestion.

    PubMed

    Dessì, S; Batetta, B; Spano, O; Pulisci, D; Mulas, M F; Muntoni, S; Armeni, M; Sanna, C; Antonucci, R; Pani, P

    1992-04-01

    In the present study, plasma lipid concentrations were determined at different times after admission in sera from G6PD-deficient children during haemolytic crisis induced by fava bean ingestion. Reductions in total, LDL and HDL cholesterol were found in association with the maximum of bone marrow hyperplasia. A return towards normal values occurred with regression of the disease. No changes in other lipid parameters were observed. These data suggest that alterations of lipoprotein pattern, other than in experimental animals, are also present in humans with non-malignant proliferative processes. These changes appear to be a consequence of the disease, probably due to an increased utilization of cholesterol by proliferating cells.

  15. Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins

    PubMed Central

    Swanson, Nancy L.; Li, Chen

    2016-01-01

    Osteonecrosis of the jaw (ONJ), a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA's Adverse Event Reporting System (FAERS) provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren's syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD) deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process. PMID:27773962

  16. Cost-effectiveness analysis of rapid diagnostic tests for G6PD deficiency in patients with Plasmodium vivax malaria in the Brazilian Amazon.

    PubMed

    Peixoto, Henry M; Brito, Marcelo A M; Romero, Gustavo A S; Monteiro, Wuelton M; de Lacerda, Marcus V G; de Oliveira, Maria R F

    2016-02-11

    The use of primaquine (PQ) for radical treatment of Plasmodium vivax in carriers of G6PD deficiency (G6PDd) constitutes the main factor associated with severe haemolysis in G6PDd. The current study aimed to estimate the incremental cost-effectiveness ratio of using a rapid diagnostic test (RDT) to detect G6PDd in male patients with P. vivax malaria in the Brazilian Amazon, in comparison with the routine indicated by the Programme for Malaria Control, which does not include this evaluation. A cost-effectiveness analysis of estimated RDT use was carried out for the Brazilian Amazon for the year 2013, considering the perspective of the Brazilian Public Health System. Using decision trees, estimates were compared for two different RDT strategies for G6PDd in male individuals infected with P. vivax before being prescribed PQ, with the routine indicated in Brazil, which does not include prior diagnosis of G6PDd. The first strategy considered the combined use of RDT BinaxNOW(®) G6PD (BX-G6PD) in municipalities with more than 100,000 inhabitants and the routine programme (RP) for the other municipalities. Operational limitations related to the required temperature control and venous blood collection currently restrict the use of RDT BX-G6PD in small municipalities. The second strategy considered the use of the RDT CareStart™ G6PD (CS-G6PD) in 100 % of the municipalities. The analysis was carried out for the outcomes: "adequately diagnosed case" and "hospitalization avoided". For the outcome "adequately diagnosed case", comparing the RDT strategies based on RDT with the routine control programme (RP), the CS-G6PD strategy was the most cost-effective, with BX-G6PD extendedly dominating (the ICER of BX-G6PD compared with RP was higher than the ICER of CS-G6PD compared with RP). CS-G6PD dominated the other strategies for the "hospitalization avoided" outcome. The CS-G6PD strategy is cost-effective for adequately diagnosing cases and avoiding hospitalization. This

  17. Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Albanian ethnic minority of Cosenza province, Italy.

    PubMed

    Tagarelli, A; Cittadella, R; Bria, M; Brancati, C

    1992-01-01

    The Albanian ethnic minority of the Cosenza province (Calabria, Southern Italy) is constituted by a population of 42,305 inhabitants living in 19 communes. The first presence of this population, in Southern Italy, dates back to the fifteenth century as a result of different immigrations. We have studied the G6PD in the population of this province by determining both the frequency of the G6PD-deficiency and the type of Gd(-) alleles in samples from 19 communes. The overall frequency estimate turned out to be 0.0294 and those of the 8 highland communes and of the 11 communes located in the valleys were 0.0242 and 0.033 respectively. Both the frequencies and the ratio between the frequencies of the different Gd(-) alleles are significantly different with respect to a previous study carried out on the non-Albanian population of the same areas. The high endogamy rate found among the grandparents' and among the parents of the probands living in the Albanian community, shows that this community is to a large extent reproductively isolated from the neighbouring populations, thus accounting for these differences.

  18. Serum lipoprotein pattern as modified in G6PD-deficient children during haemolytic anaemia induced by fava bean ingestion.

    PubMed Central

    Dessì, S.; Batetta, B.; Spano, O.; Pulisci, D.; Mulas, M. F.; Muntoni, S.; Armeni, M.; Sanna, C.; Antonucci, R.; Pani, P.

    1992-01-01

    In the present study, plasma lipid concentrations were determined at different times after admission in sera from G6PD-deficient children during haemolytic crisis induced by fava bean ingestion. Reductions in total, LDL and HDL cholesterol were found in association with the maximum of bone marrow hyperplasia. A return towards normal values occurred with regression of the disease. No changes in other lipid parameters were observed. These data suggest that alterations of lipoprotein pattern, other than in experimental animals, are also present in humans with non-malignant proliferative processes. These changes appear to be a consequence of the disease, probably due to an increased utilization of cholesterol by proliferating cells. PMID:1571275

  19. Prevalence and molecular characterization of G6PD deficiency in two Plasmodium vivax endemic areas in Venezuela: predominance of the African A-(202A/376G) variant.

    PubMed

    Vizzi, Esmeralda; Bastidas, Gilberto; Hidalgo, Mariana; Colman, Laura; Pérez, Hilda A

    2016-01-11

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency causes acute haemolytic anaemia triggered by oxidative drugs such as primaquine (PQ), used for Plasmodium vivax malaria radical cure. However, in many endemic areas of vivax malaria, patients are treated with PQ without any evaluation of their G6PD status. G6PD deficiency and its genetic heterogeneity were evaluated in northeastern and southeastern areas from Venezuela, Cajigal (Sucre state) and Sifontes (Bolívar state) municipalities, respectively. Blood samples from 664 randomly recruited unrelated individuals were screened for G6PD activity by a quantitative method. Mutation analysis for exons 4-8 of G6PD gen was performed on DNA isolated from G6PD-deficient (G6PDd) subjects through PCR-RFLP and direct DNA sequencing. Quantitative biochemical characterization revealed that overall 24 (3.6%) subjects were G6PDd (average G6PD enzyme activity 4.5 ± 1.2 U/g Hb, moderately deficient, class III), while DNA analysis showed one or two mutated alleles in 19 of them (79.2%). The G6PD A-(202A/376G) variant was the only detected in 17 (70.8%) individuals, 13 of them hemizygous males and four heterozygous females. Two males carried only the 376A → G mutation. No other mutation was found in the analysed exons. The G6PDd prevalence was as low as that one shown by nearby countries. This study contributes to the knowledge of the genetic background of Venezuelan population, especially of those living in malaria-endemic areas. Despite the high degree of genetic mixing described for Venezuelan population, a net predominance of the mild African G6PD A-(202A/376G) variant was observed among G6PDd subjects, suggesting a significant flow of G6PD genes from Africa to Americas, almost certainly introduced through African and/or Spanish immigrants during and after the colonization. The data suggest that 1:27 individuals of the studied population could be G6PDd and therefore at risk of haemolysis under precipitating factors

  20. Severe Malaria Complicated by G6PD Deficiency in a Pediatric Tanzanian Immigrant

    PubMed Central

    Damhoff, Heather N.; Stadler, Laura P.

    2014-01-01

    Approximately 1,500 cases of malaria are diagnosed in the United States each year. Most cases are travelers and immigrants returning from parts of the world where malaria transmission occurs. Malaria is the most frequent cause of systemic febrile illness without localizing symptoms in travelers returning from the developing world, so vigilance by providers is needed when evaluating patients returning from areas in which malaria is endemic. Despite the availability of effective treatment, malaria still accounts for more than 1 million deaths per year worldwide, with rates being disproportionately high in young children under the age of 5. We present the case of a 4-year-old refugee who emigrated from Tanzania with severe malaria due to dual infections of Plasmodium falciparum and P. ovale, whose treatment course was complicated by quinidine gluconate cardiotoxicity and glucose-6-phosphate dehydrogenase deficiency. PMID:25762879

  1. The use of primaquine in malaria infected patients with red cell glucose-6-phosphate dehydrogenase (G6PD) deficiency in Myanmar.

    PubMed

    Myat-Phone-Kyaw; Myint-Oo; Aung-Naing; Aye-Lwin-Htwe

    1994-12-01

    32 subjects with Plasmodium falciparum gametocytes, and 31 cases with Plasmodium vivax infection from two military hospitals (Lashio, Mandalay) were treated with quinine 600 mg three times a day for 7 days followed by primaquine 45 mg single dose for gametocytes and 45 mg weekly x 8 weeks for vivax malaria. Although screening of red cell glucose-6-phosphate dehydrogenase (G6PD) was done prior to primaquine treatment, G6PD deficient subjects were not excluded from the trial. 20 patients hemizygous for mild G6PD deficiency (GdB- variant), 2 patients hemizygous for severe deficiency (Gd-Myanmar variant) completed the trial. No case of acute hemolysis was observed in all 22 patients with two genotypes of red cell G6PD deficiency status. Therefore, a single dose of primaquine 45 mg and/or weekly for 8 weeks is adequate for the treatment of patients with P. falciparum gametocytes and/or P. vivax malaria ignoring these red cell G6PD enzyme deficient variants in Myanmar.

  2. Diospyros lotus L. fruit extract protects G6PD-deficient erythrocytes from hemolytic injury in vitro and in vivo: prevention of favism disorder.

    PubMed

    Azadbakht, M; Hosseinimehr, S J; Shokrzadeh, M; Habibi, E; Ahmadi, A

    2011-11-01

    The aim of this study was to evaluate the protective effect of Diospyros lotus L. fruit extract against the hemolytic damage induced by Vicia faba beans extract in both G6PD enzyme-deficient human and rat erythrocyte in vitro and in vivo. In the former model, venous blood samples were obtained from five subjects with known G6PD deficiency and erythrocyte hemolysis induced by Vicia faba L. bean extract was asessed spectrophotometrically in the presence and absence of Diospyros lotus L. fruits extract. In the in vivo model, G6PD-deficient rats (induced by intraperitoneal injection of dehydroepiandrosterone for 35 days) pre-treated with different doses of Diospyros lotus L. (500, 750, 1000, and 1500 mg/kg, p.o for 7 days) were challenged with Vicia faba beans extract and the protective effect of the fruit extract against hemolysis was evaluated as above. The results have shown that Diospyros lotus L. fruits extract has antioxidant activity that may protect against hemolytic damage induced by Vicia faba bean extract in both G6PD-deficient human and rat erythrocytes. The study gives a scientific basis for the efficacy of the fruit extract as used in Iran. The fact that this was shown in human erythrocytes in vitro is significant and provides a rationale for further testing in vivo in G6PD-deficient human populations.

  3. Molecular Heterogeneity of Glucose-6-Phosphate Dehydrogenase Deficiency in Burkina Faso: G-6-PD Betica Selma and Santamaria in People with Symptomatic Malaria in Ouagadougou

    PubMed Central

    Ouattara, Abdoul Karim; Yameogo, Pouiré; Diarra, Birama; Obiri-Yeboah, Dorcas; Yonli, Albert; Compaore, Tegwindé Rebeca; Soubeiga, Serge Théophile; Djigma, Florencia Wenkuuni; Simpore, Jacques

    2016-01-01

    The G-6-PD deficiency has an important polymorphism with genotypic variants such as 202A/376G, 376G/542T and 376G/968T known in West African populations. It would confer protection against severe forms of malaria although there are differences between the various associations in different studies. In this study we genotyped six (06) variants of the G-6-PD gene in people with symptomatic malaria in urban areas in Burkina Faso. One hundred and eighty-two (182) patients who tested positive using rapid detection test and microscopy were included in this study. A regular PCR with the GENESPARK G6PD African kit was run followed by electrophoresis, allowing initially to genotype six SNPs (G202A, A376G, A542T, G680T, C563T and T968C). Women carrying the mutations 202A and/or 376G were further typed by real-time PCR using TaqMan probes rs1050828 and rs1050829. In the study population the G-6-PD deficiency prevalence was 9.9%. In addition of G-6-PD A- (202A/376G) variant, 376G/542T and 376G/968T variants were also detected. Hemoglobin electrophoresis revealed that 22.5% (41/182) of the individuals had HbAC compared with2.2% with HbAS and one individual had double heterozygous HbSC. There was no correlation between the G-6-PD deficiency or haemoglobinopathies and symptomatic malaria infections in this study. Our study confirms that the G-6-PD deficiency does not confer protection against Plasmodium falciparum infections. As opposed to previous genotyping studies carried out in Burkina Faso, this study shows for the first time the presence of the variant A- (376G/968C) and warrants further investigation at the national level and in specific ethnic groups. PMID:27413522

  4. Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

    PubMed

    Pornprasert, Sakorn; Wanachantararak, Phenphichar; Kantawong, Fahsai; Chamnanprai, Supoj; Kongpan, Chatpat; Pienthai, Nattasit; Yanola, Jintana; Duangmano, Suwit; Prasannarong, Mujalin

    2016-06-18

    Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P < 0.001) higher levels of mean fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.

  5. Life and Death of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficient Erythrocytes - Role of Redox Stress and Band 3 Modifications.

    PubMed

    Arese, Paolo; Gallo, Valentina; Pantaleo, Antonella; Turrini, Franco

    2012-10-01

    G6PD catalyzes the first, pace-making reaction of pentosephosphate cycle (PPC) which produces NADPH. NADPH maintains glutathione and thiol groups of proteins and enzymes in the reduced state which is essential for protection against oxidative stress. Individuals affected by G6PD deficiency are unable to regenerate reduced glutathione (GSH) and are undefended against oxidative stress. G6PD deficiency accelerates normal senescence and enhances the precocious removal of chronologically young, yet biologically old cells. The term hemolytic anemia is misleading because RBCs do not lyse but are removed by phagocytosis. Acute hemolysis by fava bean ingestion in G6PD deficient individuals (favism) is described being the best-studied natural model of oxidant damage. It bears strong analogies to hemolysis by oxidant drugs or chemicals. Membrane alterations observed in vivo during favism are superimposable to changes in senescent RBCs. In summary, RBC membranes isolated from favic patients contained elevated amounts of complexes between IgG and the complement fragment C3b/C3c and were prone to vesiculation. Anti-band 3 IgG reacted to aggregated band 3-complement complexes. In favism extensive clustering of band 3 and membrane deposition of hemichromes were also observed. Severely damaged RBCs isolated from early crises had extensive membrane cross-bonding and very low GSH levels and were phagocytosed 10-fold more intensely compared to normal RBCs.

  6. Life and Death of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficient Erythrocytes – Role of Redox Stress and Band 3 Modifications

    PubMed Central

    Arese, Paolo; Gallo, Valentina; Pantaleo, Antonella; Turrini, Franco

    2012-01-01

    Summary G6PD catalyzes the first, pace-making reaction of pentosephosphate cycle (PPC) which produces NADPH. NADPH maintains glutathione and thiol groups of proteins and enzymes in the reduced state which is essential for protection against oxidative stress. Individuals affected by G6PD deficiency are unable to regenerate reduced glutathione (GSH) and are undefended against oxidative stress. G6PD deficiency accelerates normal senescence and enhances the precocious removal of chronologically young, yet biologically old cells. The term hemolytic anemia is misleading because RBCs do not lyse but are removed by phagocytosis. Acute hemolysis by fava bean ingestion in G6PD deficient individuals (favism) is described being the best-studied natural model of oxidant damage. It bears strong analogies to hemolysis by oxidant drugs or chemicals. Membrane alterations observed in vivo during favism are superimposable to changes in senescent RBCs. In summary, RBC membranes isolated from favic patients contained elevated amounts of complexes between IgG and the complement fragment C3b/C3c and were prone to vesiculation. Anti-band 3 IgG reacted to aggregated band 3-complement complexes. In favism extensive clustering of band 3 and membrane deposition of hemichromes were also observed. Severely damaged RBCs isolated from early crises had extensive membrane cross-bonding and very low GSH levels and were phagocytosed 10-fold more intensely compared to normal RBCs. PMID:23801924

  7. Disease-modifying influences of coexistent G6PD-deficiency, Gilbert syndrome and deletional alpha thalassemia in hereditary spherocytosis: A report of three cases.

    PubMed

    Jamwal, Manu; Aggarwal, Anu; Kumar, Verinder; Sharma, Prashant; Sachdeva, Man Updesh Singh; Bansal, Deepak; Malhotra, Pankaj; Das, Reena

    2016-07-01

    Hereditary spherocytosis (HS) is a common inherited hemolytic anemia characterized by heterogeneous clinical presentations with variable degrees of anemia, jaundice, splenomegaly and gallstones. Although the underlying genetic defects in red cell membrane proteins may explain many phenotypic variations, a proportion of variability may be due to other co-inherited factors like enzymopathies, thalassemias and Gilbert syndrome. Associations of HS with glucose-6-phosphate dehydrogenase (G6PD) deficiency and Gilbert syndrome in isolation have been reported previously. We describe 3 adult cases of HS with concomitant Gilbert syndrome and G6PD-Mediterranean mutations (2 hemizygous males, aged 15 and 35y and 1 heterozygous 25-y female). Two patients required multiple transfusions that required splenectomy for management. One patient (15y male) also carried the single gene alpha 4.2 deletion and was less symptomatic. These cases illustrate the importance of clinico-pathological correlation and judicious extended testing for various contributing factors that may modify the clinical course of HS patients. G6PD deficiency is also a common enzymopathy in India and can contribute to the phenotypic heterogeneity. Its recognition is important for advising avoidance of oxidizing drug exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. G6PD deficiency and absence of α-thalassemia increase the risk for cerebral vasculopathy in children with sickle cell anemia.

    PubMed

    Joly, Philippe; Garnier, Nathalie; Kebaili, Kamila; Renoux, Céline; Dony, Arthur; Cheikh, Nathalie; Renard, Cécile; Ceraulo, Antony; Cuzzubbo, Daniela; Pondarré, Corinne; Martin, Cyril; Pialoux, Vincent; Francina, Alain; Bertrand, Yves; Connes, Philippe

    2016-04-01

    The aim of this study was to test the association between hematological/genetic factors and cerebral vasculopathy in children with sickle cell anemia (SCA). A group with cerebral vasculopathy (VASC) was composed of children who had stroke (n = 6), silent infarct (n = 11), or an abnormal transcranial Doppler (n = 5). Eighty-four patients had neither positive history of stroke or silent infarct, nor abnormal transcranial Doppler (NORM group). An intermediate group (COND; n = 15) was composed of SCA children with a conditional transcranial Doppler. Biological analyses were performed on samples obtained at steady state and before the beginning of any chronic treatment. The comparisons of the three groups demonstrated a protective effect of α-thalassemia against cerebral vasculopathy through its effects on hemoglobin and reticulocyte levels. Moreover, we observed higher frequency of G6PD deficiency in the VASC group compared with the other groups. Our study confirms the key role of α-thalassemia and G6PD status in the pathophysiology of cerebral vasculopathy in SCA children.

  9. G6PD: The Test

    MedlinePlus

    ... initial findings. Screening tests typically involve a simple qualitative test that only tells if the person has ... this testing is used almost exclusively in the research setting. G6PD testing should not be done soon ...

  10. The challenges of introducing routine G6PD testing into radical cure: a workshop report.

    PubMed

    Ley, Benedikt; Luter, Nick; Espino, Fe Esperanza; Devine, Angela; Kalnoky, Michael; Lubell, Yoel; Thriemer, Kamala; Baird, J Kevin; Poirot, Eugenie; Conan, Nolwenn; Kheong, Chong Chee; Dysoley, Lek; Khan, Wasif Ali; Dion-Berboso, April G; Bancone, Germana; Hwang, Jimee; Kumar, Ritu; Price, Ric N; von Seidlein, Lorenz; Domingo, Gonzalo J

    2015-09-29

    The only currently available drug that effectively removes malaria hypnozoites from the human host is primaquine. The use of 8-aminoquinolines is hampered by haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Recently a number of qualitative and a quantitative rapid diagnostic test (RDT) format have been developed that provide an alternative to the current standard G6PD activity assays. The WHO has recently recommended routine testing of G6PD status prior to primaquine radical cure whenever possible. A workshop was held in the Philippines in early 2015 to discuss key challenges and knowledge gaps that hinder the introduction of routine G6PD testing. Two point-of-care (PoC) test formats for the measurement of G6PD activity are currently available: qualitative tests comparable to malaria RDT as well as biosensors that provide a quantitative reading. Qualitative G6PD PoC tests provide a binomial test result, are easy to use and some products are comparable in price to the widely used fluorescent spot test. Qualitative test results can accurately classify hemizygous males, heterozygous females, but may misclassify females with intermediate G6PD activity. Biosensors provide a more complex quantitative readout and are better suited to identify heterozygous females. While associated with higher costs per sample tested biosensors have the potential for broader use in other scenarios where knowledge of G6PD activity is relevant as well. The introduction of routine G6PD testing is associated with additional costs on top of routine treatment that will vary by setting and will need to be assessed prior to test introduction. Reliable G6PD PoC tests have the potential to play an essential role in future malaria elimination programmes, however require an improved understanding on how to best integrate routine G6PD testing into different health settings.

  11. G6PD Deficiency Prevalence and Estimates of Affected Populations in Malaria Endemic Countries: A Geostatistical Model-Based Map

    PubMed Central

    Howes, Rosalind E.; Piel, Frédéric B.; Patil, Anand P.; Nyangiri, Oscar A.; Gething, Peter W.; Dewi, Mewahyu; Hogg, Mariana M.; Battle, Katherine E.; Padilla, Carmencita D.; Baird, J. Kevin; Hay, Simon I.

    2012-01-01

    Background Primaquine is a key drug for malaria elimination. In addition to being the only drug active against the dormant relapsing forms of Plasmodium vivax, primaquine is the sole effective treatment of infectious P. falciparum gametocytes, and may interrupt transmission and help contain the spread of artemisinin resistance. However, primaquine can trigger haemolysis in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information is available about the distribution of individuals at risk of primaquine-induced haemolysis. We present a continuous evidence-based prevalence map of G6PDd and estimates of affected populations, together with a national index of relative haemolytic risk. Methods and Findings Representative community surveys of phenotypic G6PDd prevalence were identified for 1,734 spatially unique sites. These surveys formed the evidence-base for a Bayesian geostatistical model adapted to the gene's X-linked inheritance, which predicted a G6PDd allele frequency map across malaria endemic countries (MECs) and generated population-weighted estimates of affected populations. Highest median prevalence (peaking at 32.5%) was predicted across sub-Saharan Africa and the Arabian Peninsula. Although G6PDd prevalence was generally lower across central and southeast Asia, rarely exceeding 20%, the majority of G6PDd individuals (67.5% median estimate) were from Asian countries. We estimated a G6PDd allele frequency of 8.0% (interquartile range: 7.4–8.8) across MECs, and 5.3% (4.4–6.7) within malaria-eliminating countries. The reliability of the map is contingent on the underlying data informing the model; population heterogeneity can only be represented by the available surveys, and important weaknesses exist in the map across data-sparse regions. Uncertainty metrics are used to quantify some aspects of these limitations in the map. Finally, we assembled a database of G6PDd variant occurrences to inform a national-level index of

  12. G6PD (Dublin): chronic non-spherocytic haemolytic anaemia resulting from glucose-6-phosphate dehydrogenase deficiency in an Irish kindred.

    PubMed Central

    McCann, S R; Smithwick, A M; Temperley, I J; Tipton, K

    1980-01-01

    A new variant of G6PD associated with chronic non-spherocytic haemolytic anaemia (CNSHA) in an Irish male is described. This variant is unique in that it has a normal electrophoretic mobility, Michaelis constant for G6P and NADP, and a normal pH optimum, together with a marked increase in utilisation of the substrate 2 deoxy glucose-6-phosphate. It is also relatively heat stable when compared with the normal (B) variant. These characteristics distinguish this variant from previously reported variants associated with CNSHA and we have called it G6PD Dublin. PMID:7401130

  13. Rapid diagnostic test for G6PD deficiency in Plasmodium vivax-infected men: a budget impact analysis based in Brazilian Amazon.

    PubMed

    Peixoto, Henry Maia; Brito, Marcelo Augusto Mota; Romero, Gustavo Adolfo Sierra; Monteiro, Wuelton Marcelo; de Lacerda, Marcus Vinícius Guimarães; de Oliveira, Maria Regina Fernandes

    2017-01-01

    The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared with the routine protocol recommended in Brazil which does not include G6PDd testing. The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart™ G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria. The expected implementation of the diagnostic test was 30% in the first year, 70% the second year and 100% in the third year. The analysis identified negative IBIs which were progressively smaller in the 3 years evaluated. The sensitivity analysis showed that the uncertainties associated with the analytical model did not significantly affect the results. A strategy based on the use of CS-G6PD would result in better use of public resources in the Brazilian Amazon. © 2016 John Wiley & Sons Ltd.

  14. Comparison of Three Screening Test Kits for G6PD Enzyme Deficiency: Implications for Its Use in the Radical Cure of Vivax Malaria in Remote and Resource-Poor Areas in the Philippines

    PubMed Central

    Espino, Fe Esperanza; Sornillo, Johanna Beulah; Tan, Alvin; von Seidlein, Lorenz

    2016-01-01

    Objective We evaluated a battery of Glucose-6-Phosphate Dehydrogenase diagnostic point-of-care tests (PoC) to assess the most suitable product in terms of performance and operational characteristics for remote areas. Methods Samples were collected in Puerto Princesa City, Palawan, Philippines and tested for G6PD deficiency with a fluorescent spot test (FST; Procedure 203, Trinity Biotech, Ireland), the semiquantitative WST8/1-methoxy PMS (WST; Dojindo, Japan) and the Carestart G6PD Rapid Diagnostic Test (CSG; AccessBio, USA). Results were compared to spectrophotometry (Procedure 345, Trinity Biotech, Ireland). Sensitivity and specificity were calculated for each test with cut-off activities of 10%, 20%, 30% and 60% of the adjusted male median. Results The adjusted male median was 270.5 IU/1012 RBC. FST and WST were tested on 621 capillary blood samples, the CSG was tested on venous and capillary blood on 302 samples. At 30% G6PD activity, sensitivity for the FST was between 87.7% (95%CI: 76.8% to 93.9%) and 96.5% (95%CI: 87.9% to 99.5%) depending on definition of intermediate results; the WST was 84.2% (95%CI: 72.1% to 92.5%); and the CSG was between 68.8% (95%CI: 41.3% to 89.0%) and 93.8% (95%CI: 69.8% to 99.8%) when the test was performed on capillary or venous blood respectively. Sensitivity of FST and CSG (tested with venous blood) were comparable (p>0.05). The analysis of venous blood samples by the CSG yielded significantly higher results than FST and CSG performed on capillary blood (p<0.05). Sensitivity of the CSG varied depending on source of blood used (p<0.05). Conclusion The operational characteristics of the CSG were superior to all other test formats. Performance and operational characteristics of the CSG performed on venous blood suggest the test to be a good alternative to the FST. PMID:26849445

  15. G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests

    PubMed Central

    2013-01-01

    Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as “radical cure”), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide. Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient’s G6PD status is known before deciding to administer an 8-aminoquinoline-based drug. In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure. PMID:24188096

  16. Birth control necessary to limit family size in tribal couples with aberrant heterosis of G-6-PD deficiency and sickle cell disorders in India: an urgency of creating awareness and imparting genetic counseling.

    PubMed

    Balgir, R S

    2010-06-01

    (i) To study the outcome of ignorance and lack of awareness about sickle cell disease and G-6-PD deficiency among Dhelki Kharia tribal families of Orissa, and (ii) to study the reproductive output in relation to clinical genetics and patho-physiological implications. A random genetic study of screening for hemoglobinopathies and G-6-PD deficiency among Dhelki Kharia tribal community in Sundargarh district of Orissa was carried out for intervention during the year 2000-2004. A total of 81 Dhelki Kharia families were screened and six families with double heterozygosity for above genetic anomalies were encountered. About 2-3 ml. intravenous blood samples were collected in EDTA by disposable syringes and needles after taking informed consent from each individual in the presence of a doctor and community leaders and sent to laboratory at Bhubaneswar for hematological investigations. Analysis was carried out following the standard procedures after cross checking for quality control. There were 12 (about 52%) children out of 23 who were either suffering from sickle cell trait or disease in concurrence with G-6-PD deficiency in hemizygous/heterozygous/homozygous condition in Dhelki Kharia tribal community of Orissa. There were on an average 3.83 number of surviving (range 2-6) children per mother in families of G-6-PD deficiency and sickle cell disorders. The average number of children (3.83) born (range 2-6 children) per mother to carrier/affected mother was much higher than the average for India (2.73). It is very difficult to maintain the normal health of an affected child with aberrant anomalies due to exorbitant cost of treatment, frequent transfusions and huge involvement of economy. One of the implications of aberrant heterosis is its adverse affects on routine individual physiology and hard activities. It is suggested to limit the family size in carrier couples to avoid aberrant heterosis of hereditary hemolytic disorders in their offsprings.

  17. Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells

    PubMed Central

    Akide-Ndunge, Oscar Bate; Tambini, Elisa; Giribaldi, Giuliana; McMillan, Paul J; Müller, Sylke; Arese, Paolo; Turrini, Francesco

    2009-01-01

    Background Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Methods Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70–2/70–3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. Results In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs

  18. Activity of divicine in Plasmodium vinckei-infected mice has implications for treatment of favism and epidemiology of G-6-PD deficiency.

    PubMed

    Clark, I A; Cowden, W B; Hunt, N H; Maxwell, L E; Mackie, E J

    1984-07-01

    Intravenous injection of divicine into mice infected with Plasmodium vinckei rapidly killed the parasites and caused haemolysis. Degenerating parasites were observed frequently inside intact circulating erythrocytes, implying that parasite death was not a passive consequence of haemolysis. Both parasite death and haemolysis were prevented by the iron chelator desferrioxamine. In vitro, divicine caused the accumulation of malonyldialdehyde and the depletion of reduced glutathione in normal mouse erythrocytes. Desferrioxamine inhibited the former event, but not the latter. These observations support the hypothesis advanced by Huheey & Martin (Experientia, 31, 1145, 1975) to explain the patchy geographical distribution of glucose-6-phosphate dehydrogenase deficiency in historic malarial areas and also suggest that desferrioxamine, a drug already in clinical use, is a potential treatment for favism and other examples of oxidative haemolysis.

  19. A prolonged neonatal jaundice associated with a rare G6PD mutation.

    PubMed

    Minucci, Angelo; Concolino, Paola; De Luca, Daniele; Giardina, Bruno; Zuppi, Cecilia; Capoluongo, Ettore

    2009-09-01

    Glucose-6-phosphate dehydrogenase (G6PD), a X-linked hereditary deficiency, is one of most common clinically significant enzyme defects. Despite its largely known role in acute and life-threatening haemolytic crises, G6PD deficiency may be also associated with neonatal jaundice that, when severe and untreated, may lead to the potential of bilirubin encephalopathy. A prolonged neonatal jaundice was found to be associated with a rare G6PD mutation (c.383T>G; p.L128R), the latter simply annotated in literature database. In this article, we clinically and phenotipically describe a case of an Italian neonate carrying the c.383T>G G6PD mutation. Finally, we named this variant "G6PD Salerno." (c) 2009 Wiley-Liss, Inc.

  20. National G6PD neonatal screening program in Gaza Strip of Palestine: rationale, challenges and recommendations.

    PubMed

    Sirdah, M M; Al-Kahlout, M S; Reading, N S

    2016-09-01

    Congenital genetic disorders affecting neonates or young children can have serious clinical consequences if undiagnosed and left untreated. Early detection and an accurate diagnosis are, therefore, of major importance for preventing negative patient outcomes. Even though the occurrence of each specific metabolic disorder may be rare, their collective impact of preventable complications may be of considerable importance to the public health. Our previous studies showed that glucose-6-phosphate dehydrogenase (G6PD) deficiency is a problem of public health importance that has been shown to be a predominant cause of acute hemolytic anemia requiring hospitalization in Palestinian young children in Gaza Strip. Intriguingly, the majority of these children had one of the three variants, Mediterranean(c.) (563T) , African G6PD A-(c.) (202A) (/c.) (376G) and heretofore unrecognized as a common G6PD-deficient variant G6PD Cairo(c.) (404C) . The high prevalence of G6PD deficiency, as well as dietary factors in the region that precipitate anemia, argues for a need to protect the Palestinian children from a treatable and manageable genetic and metabolic disorder. This work reviews and discusses rationales and challenges of G6PD screening program in Gaza Strip. We advocate adopting a national neonatal G6PD screening program in Gaza Strip to identify children at risk and promote wellness and health for Palestine. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Barriers to routine G6PD testing prior to treatment with primaquine.

    PubMed

    Ley, Benedikt; Thriemer, Kamala; Jaswal, Jessica; Poirot, Eugenie; Alam, Mohammad Shafiul; Phru, Ching Swe; Khan, Wasif Ali; Dysoley, Lek; Qi, Gao; Kheong, Chong Chee; Shamsudin, Ummi Kalthom; Chen, Ingrid; Hwang, Jimee; Gosling, Roly; Price, Ric N

    2017-08-10

    Primaquine is essential for the radical cure of vivax malaria, however its broad application is hindered by the risk of drug-induced haemolysis in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. Rapid diagnostic tests capable of diagnosing G6PD deficiency are now available, but these are not used widely. A series of qualitative interviews were conducted with policy makers and healthcare providers in four vivax-endemic countries. Routine G6PD testing is not part of current policy in Bangladesh, Cambodia or China, but it is in Malaysia. The interviews were analysed with regard to respondents perceptions of vivax malaria, -primaquine based treatment for malaria and the complexities of G6PD deficiency. Three barriers to the roll-out of routine G6PD testing were identified in all sites: (a) a perceived low risk of drug-induced haemolysis; (b) the perception that vivax malaria was benign and accordingly treatment with primaquine was not regarded as a priority; and, (c) the additional costs of introducing routine testing. In Malaysia, respondents considered the current test and treat algorithm suitable and the need for an alternative approach was only considered relevant in highly mobile and hard to reach populations. Greater efforts are needed to increase awareness of the benefits of the radical cure of Plasmodium vivax and this should be supported by economic analyses exploring the cost effectiveness of routine G6PD testing.

  2. Characterization of G6PD Genotypes and Phenotypes on the Northwestern Thailand-Myanmar Border

    PubMed Central

    Somsakchaicharoen, Raweewan; Chowwiwat, Nongnud; Parker, Daniel M.; Charunwatthana, Prakaykaew; White, Nicholas J.; Nosten, François H.

    2014-01-01

    Mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST), G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A) genotype. The remaining subjects had Chinese-4 (392G>T), Viangchan (871G>A), Açores (595A>G), Seattle (844G>C) and Mediterranean (563C>T) variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes. PMID:25536053

  3. Evidence for Balancing Selection from Nucleotide Sequence Analyses of Human G6PD

    PubMed Central

    Verrelli, Brian C.; McDonald, John H.; Argyropoulos, George; Destro-Bisol, Giovanni; Froment, Alain; Drousiotou, Anthi; Lefranc, Gerard; Helal, Ahmed N.; Loiselet, Jacques; Tishkoff, Sarah A.

    2002-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) mutations that result in reduced enzyme activity have been implicated in malarial resistance and constitute one of the best examples of selection in the human genome. In the present study, we characterize the nucleotide diversity across a 5.2-kb region of G6PD in a sample of 160 Africans and 56 non-Africans, to determine how selection has shaped patterns of DNA variation at this gene. Our global sample of enzymatically normal B alleles and A, A−, and Med alleles with reduced enzyme activities reveals many previously uncharacterized silent-site polymorphisms. In comparison with the absence of amino acid divergence between human and chimpanzee G6PD sequences, we find that the number of G6PD amino acid polymorphisms in human populations is significantly high. Unlike many other G6PD-activity alleles with reduced activity, we find that the age of the A variant, which is common in Africa, may not be consistent with the recent emergence of severe malaria and therefore may have originally had a historically different adaptive function. Overall, our observations strongly support previous genotype-phenotype association studies that proposed that balancing selection maintains G6PD deficiencies within human populations. The present study demonstrates that nucleotide sequence analyses can reveal signatures of both historical and recent selection in the genome and may elucidate the impact that infectious disease has had during human evolution. PMID:12378426

  4. A Comparison of Three Quantitative Methods to Estimate G6PD Activity in the Chittagong Hill Tracts, Bangladesh

    PubMed Central

    Ley, Benedikt; Alam, Mohammad Shafiul; O’Donnell, James J.; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Jahan, Nusrat; Khan, Wasif A.; Thriemer, Kamala; Chatfield, Mark D.; Price, Ric N.; Richards, Jack S.

    2017-01-01

    Background Glucose-6-phosphate-dehydrogenase-deficiency (G6PDd) is a major risk factor for primaquine-induced haemolysis. There is a need for improved point-of-care and laboratory-based G6PD diagnostics to unsure safe use of primaquine. Methods G6PD activities of participants in a cross-sectional survey in Bangladesh were assessed using two novel quantitative assays, the modified WST-8 test and the CareStart™ G6PD Biosensor (Access Bio), The results were compared with a gold standard UV spectrophotometry assay (Randox). The handheld CareStart™ Hb instrument (Access Bio) is designed to be a companion instrument to the CareStart™ G6PD biosensor, and its performance was compared to the well-validated HemoCue™ method. All quantitative G6PD results were normalized with the HemoCue™ result. Results A total of 1002 individuals were enrolled. The adjusted male median (AMM) derived by spectrophotometry was 7.03 U/g Hb (interquartile range (IQR): 5.38–8.69), by WST-8 was 7.03 U/g Hb (IQR: 5.22–8.16) and by Biosensor was 8.61 U/g Hb (IQR: 6.71–10.08). The AMM between spectrophotometry and WST-8 did not differ (p = 1.0) but differed significantly between spectrophotometry and Biosensor (p<0.01). Both, WST-8 and Biosensor were correlated with spectrophotometry (rs = 0.5 and rs = 0.4, both p<0.001). The mean difference in G6PD activity was -0.12 U/g Hb (95% limit of agreement (95% LoA): -5.45 to 5.20) between spectrophotometry and WST-8 and -1.74U/g Hb (95% LoA: -7.63 to 4.23) between spectrophotometry and Biosensor. The WST-8 identified 55.1% (49/89) and the Biosensor 19.1% (17/89) of individuals with G6PD activity <30% by spectrophotometry. Areas under the ROC curve did not differ significantly for the WST-8 and Biosensor irrespective of the cut-off activity applied (all p>0.05). Sensitivity and specificity for detecting G6PD activity <30% was 0.55 (95% confidence interval (95%CI): 0.44–0.66) and 0.98 (95%CI: 0.97–0.99) respectively for the WST-8 and 0

  5. A Comparison of Three Quantitative Methods to Estimate G6PD Activity in the Chittagong Hill Tracts, Bangladesh.

    PubMed

    Ley, Benedikt; Alam, Mohammad Shafiul; O'Donnell, James J; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Jahan, Nusrat; Khan, Wasif A; Thriemer, Kamala; Chatfield, Mark D; Price, Ric N; Richards, Jack S

    2017-01-01

    Glucose-6-phosphate-dehydrogenase-deficiency (G6PDd) is a major risk factor for primaquine-induced haemolysis. There is a need for improved point-of-care and laboratory-based G6PD diagnostics to unsure safe use of primaquine. G6PD activities of participants in a cross-sectional survey in Bangladesh were assessed using two novel quantitative assays, the modified WST-8 test and the CareStart™ G6PD Biosensor (Access Bio), The results were compared with a gold standard UV spectrophotometry assay (Randox). The handheld CareStart™ Hb instrument (Access Bio) is designed to be a companion instrument to the CareStart™ G6PD biosensor, and its performance was compared to the well-validated HemoCue™ method. All quantitative G6PD results were normalized with the HemoCue™ result. A total of 1002 individuals were enrolled. The adjusted male median (AMM) derived by spectrophotometry was 7.03 U/g Hb (interquartile range (IQR): 5.38-8.69), by WST-8 was 7.03 U/g Hb (IQR: 5.22-8.16) and by Biosensor was 8.61 U/g Hb (IQR: 6.71-10.08). The AMM between spectrophotometry and WST-8 did not differ (p = 1.0) but differed significantly between spectrophotometry and Biosensor (p<0.01). Both, WST-8 and Biosensor were correlated with spectrophotometry (rs = 0.5 and rs = 0.4, both p<0.001). The mean difference in G6PD activity was -0.12 U/g Hb (95% limit of agreement (95% LoA): -5.45 to 5.20) between spectrophotometry and WST-8 and -1.74U/g Hb (95% LoA: -7.63 to 4.23) between spectrophotometry and Biosensor. The WST-8 identified 55.1% (49/89) and the Biosensor 19.1% (17/89) of individuals with G6PD activity <30% by spectrophotometry. Areas under the ROC curve did not differ significantly for the WST-8 and Biosensor irrespective of the cut-off activity applied (all p>0.05). Sensitivity and specificity for detecting G6PD activity <30% was 0.55 (95% confidence interval (95%CI): 0.44-0.66) and 0.98 (95%CI: 0.97-0.99) respectively for the WST-8 and 0.19 (95%CI: 0.12-0.29) and 0.99 (95%CI: 0

  6. [Molecular identification of glucose-6-phosphate dehydrogenase (G6PD) detected in neonatal screening].

    PubMed

    Zamorano-Jiménez, Clara Aurora; Baptista-González, Héctor Alfredo; Bouchán-Valencia, Patricia; Granados-Cepeda, Martha Lucía; Trueba-Gómez, Rocío; Coeto-Barona, Georgina; Rosenfeld-Mann, Fany; Rosa-Mireles, Luisa Blanca; Meléndez-Ramírez, Rocío

    2015-01-01

    To present the strategy of identifying the molecular variants of G6PD detected in neonatal screening (NS). We present a series of incident cases of newborns positive for G6PD deficiency detected in NS. From nuclear DNA with the methodology of real-time PCR we sought molecular G6PD variants: G202A, A376G, T968C and C563T. Of a total of 21,619 neonates, 41 cases were reactive in NS for G6PD (189.6/100,000 RN screened rate), 34 cases confirmed the molecular variant of G6PD (157.3/100,000 RN screened rate). The most frequent allele combination G202A/A376G (G6PD ratio and median activity, 0.460 and 1.72 ± 0.35 U/g Hb, respectively), followed by G202A (0.170 and 1.74 ± 0.27 U/g Hb) and A376G/T968C (ratio 0.150 and 1.10 ± 0.44 U/g Hb). The T968C allelic variant showed lower enzyme activity than the rest (1.1 ± 0.4; p = 0.02). Two women were detected with G6PD deficiency with G202A/A376G and G202A variant. African alleles were prevalently detected in neonatal screening. This strategy allows the identification of molecular variants involved in 80% of cases.

  7. A new glucose-6-phosphate dehydrogenase variant, G6PD Orissa (44 Ala{yields}Gly), is the major polymorphic variant in tribal populations in India

    SciTech Connect

    Kaeda, J.S.; Bautista, J.M.; Stevens, D.

    1995-12-01

    Deficiency of glucose-6-phosphate dehydrogenase (G6PD) is usually found at high frequencies in areas of the world where malaria has been epidemic. The frequency and genetic basis of G6PD deficiency have been studied in Africa, around the Mediterranean, and in the Far East, but little such information is available about the situation in India. To determine the extent of heterogeneity of G6PD, we have studied several different Indian populations by screening for G6PD deficiency, followed by molecular analysis of deficient alleles. The frequency of G6PD deficiency varies between 3% and 15% in different tribal and urban groups. Remarkably, a previously unreported deficient variant, G6PD Orissa (44 Ala{yields}Gly), is responsible for most of the G6PD deficiency in tribal Indian populations but is not found in urban populations, where most of the G6PD deficiency is due to the G6PD Mediterranean (188 Ser{yields}Phe) variant. The K{sup NADP}{sub m} of G6PD Orissa is fivefold higher than that of the normal enzyme. This may be due to the fact that the alanine residue that is replaced by glycine is part of a putative coenzyme-binding site. 37 refs., 2 figs., 3 tabs.

  8. Parental education and the WHO neonatal G-6-PD screening program: a quarter century later.

    PubMed

    Kaplan, M; Hammerman, C; Bhutani, V K

    2015-10-01

    Neonatal screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in any population with a male frequency >3-5%, combined with parental education regarding the dietary, environmental and sepsis-related triggers for hemolysis was recommended by the WHO (World Health Organization) Working Group in 1989. As the aim of identifying G-6-PD deficiency in the newborn period is to avert or detect extreme hyperbilirubinemia developing at home, before the development of kernicterus, the parental role in identifying evolving icterus was considered integral to any screening program. Now, a quarter century after publication of this report, severe bilirubin neurotoxicity associated with G-6-PD deficiency continues to be encountered worldwide. Screening programs have not been universally introduced but several national or regional maternal child health programs have implemented neonatal G-6-PD screening. Some reports detail the role of parental education, based on the above mentioned principles, through a variety of audio-visual materials. The paucity of randomized controlled trials or validated evidence to demonstrate the effectiveness of the contribution of parental education fails to meet the ideal testable evidence-based approach. However, our review of the cumulative experience and evidence currently available does supply certain information reflecting a positive impact of screening programs combined with parental input. We propose that the current information is sufficient to continue to support and apply the Working Group's recommendations. In order not to waste unnecessary time available, data may be used in lieu of randomized trials to continue to recommend screening programs, as suggested, in high-risk regions. If the incidence of kernicterus associated with G-6-PD deficiency is to be diminished, G-6-PD screening in combination with parental explanation may be one instance in which the consensus approach suggested by the WHO Working Group, rather than reliance

  9. [G6PD phenotype and red blood cell sensitivity to the oxidising action of chlorites in drinking water].

    PubMed

    Contu, A; Bajorek, M; Carlini, M; Meloni, P; Cocco, P; Schintu, M

    2005-01-01

    Chlorine dioxide is widely used to replace sodium hypochlorite in the disinfection of surface waters for human consumption, in order to avoid or reduce the formation of organohalogenated compounds with mutagenic and carcinogenic activity. However, chlorine dioxide may lead to the formation of by-products, such as chlorites and chlorates, that have an oxidative effect on the blood corpuscled fraction. In this investigation, blood crasis was assessed in relation to the G6PD phenotype and the consumption of tap water, disinfected with chlorine dioxide, or bottled mineral water from non-disinfected underground sources. The results show that the effect of oxidative stress resulting from the uptake of chlorites with drinking water is not additive to the effect due to G6PD deficiency. The observed change in haematological parameters, including those related to the G6PD polymorphism, is always within the normal range. However, it is still possible that more relevant changes would follow exposure to chlorites concentrations greater than that observed in the present study.

  10. Methods for the field evaluation of quantitative G6PD diagnostics: a review.

    PubMed

    Ley, Benedikt; Bancone, Germana; von Seidlein, Lorenz; Thriemer, Kamala; Richards, Jack S; Domingo, Gonzalo J; Price, Ric N

    2017-09-11

    Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of severe haemolysis following the administration of 8-aminoquinoline compounds. Primaquine is the only widely available 8-aminoquinoline for the radical cure of Plasmodium vivax. Tafenoquine is under development with the potential to simplify treatment regimens, but point-of-care (PoC) tests will be needed to provide quantitative measurement of G6PD activity prior to its administration. There is currently a lack of appropriate G6PD PoC tests, but a number of new tests are in development and are likely to enter the market in the coming years. As these are implemented, they will need to be validated in field studies. This article outlines the technical details for the field evaluation of novel quantitative G6PD diagnostics such as sample handling, reference testing and statistical analysis. Field evaluation is based on the comparison of paired samples, including one sample tested by the new assay at point of care and one sample tested by the gold-standard reference method, UV spectrophotometry in an established laboratory. Samples can be collected as capillary or venous blood; the existing literature suggests that potential differences in capillary or venous blood are unlikely to affect results substantially. The collection and storage of samples is critical to ensure preservation of enzyme activity, it is recommended that samples are stored at 4 °C and testing occurs within 4 days of collection. Test results can be visually presented as scatter plot, Bland-Altman plot, and a histogram of the G6PD activity distribution of the study population. Calculating the adjusted male median allows categorizing results according to G6PD activity to calculate standard performance indicators and to perform receiver operating characteristic (ROC) analysis.

  11. Using G6PD tests to enable the safe treatment of Plasmodium vivax infections with primaquine on the Thailand-Myanmar border: A cost-effectiveness analysis.

    PubMed

    Devine, Angela; Parmiter, Minnie; Chu, Cindy S; Bancone, Germana; Nosten, François; Price, Ric N; Lubell, Yoel; Yeung, Shunmay

    2017-05-01

    Primaquine is the only licensed antimalarial for the radical cure of Plasmodium vivax infections. Many countries, however, do not administer primaquine due to fear of hemolysis in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In other settings, primaquine is given without G6PD testing, putting patients at risk of hemolysis. New rapid diagnostic tests (RDTs) offer the opportunity to screen for G6PD deficiency prior to treatment with primaquine. Here we assessed the cost-effectiveness of using G6PD RDTs on the Thailand-Myanmar border and provide the model as an online tool for use in other settings. Decision tree models for the management of P. vivax malaria evaluated the costs and disability-adjusted life-years (DALYs) associated with recurrences and primaquine-induced hemolysis from a health care provider perspective. Screening with G6PD RDTs before primaquine use was compared to (1) giving chloroquine alone and (2) giving primaquine without screening. Data were taken from a recent study on the impact of primaquine on P. vivax recurrences and a literature review. Compared to the use of chloroquine alone, the screening strategy had similar costs while averting 0.026 and 0.024 DALYs per primary infection in males and females respectively. Compared to primaquine administered without screening, the screening strategy provided modest cost savings while averting 0.011 and 0.004 DALYs in males and females respectively. The probabilistic sensitivity analyses resulted in a greater than 75% certainty that the screening strategy was cost-effective at a willingness to pay threshold of US$500, which is well below the common benchmark of per capita gross domestic product for Myanmar. In this setting G6PD RDTs could avert DALYs by reducing recurrences and reducing hemolytic risk in G6PD deficient patients at low costs or cost savings. The model results are limited by the paucity of data available in the literature for some parameter values, including the

  12. Nine different glucose-6-phosphate dehydrogenase (G6PD) variants in a Malaysian population with Malay, Chinese, Indian and Orang Asli (aboriginal Malaysian) backgrounds.

    PubMed

    Wang, Jichun; Luo, Enjie; Hirai, Makoto; Arai, Meiji; Abdul-Manan, Eas; Mohamed-Isa, Zaleha; Hidayah, Ni; Matsuoka, Hiroyuki

    2008-10-01

    The Malaysian people consist of several ethnic groups including the Malay, the Chinese, the Indian and the Orang Asli (aboriginal Malaysians). We collected blood samples from outpatients of 2 hospitals in the State of Selangor and identified 27 glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects among these ethnic groups. In the Malay, G6PD Viangchan (871GA, 1311CT, IVS11 nt93TC) and G6PD Mahidol (487GA) types, which are common in Cambodia and Myanmar, respectively, were detected. The Malay also had both subtypes of G6PD Mediterranean:the Mediterranean subtype (563CT, 1311CT, IVS11 nt93TC) and the Indo-Pakistan subtype (563CT, 1311C, IVS11 nt93T). In Malaysians of Chinese background, G6PD Kaiping (1388GA), G6PD Canton (1376GT) and G6PD Gaohe (95AG), which are common in China, were detected. Indian Malaysians possessed G6PD Mediterranean (Indo-Pakistan subtype) and G6PD Namoru (208TC), a few cases of which had been reported in Vanuatu and many in India. Our findings indicate that G6PD Namoru occurs in India and flows to Malaysia up to Vanuatu. We also discovered 5 G6PD-deficient cases with 2 nucleotide substitutions of 1311CT and IVS11 nt93TC, but without amino-acid substitution in the G6PD molecule. These results indicate that the Malaysian people have incorporated many ancestors in terms of G6PD variants.

  13. Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress#

    PubMed Central

    Wang, Yi-Ping; Zhou, Li-Sha; Zhao, Yu-Zheng; Wang, Shi-Wen; Chen, Lei-Lei; Liu, Li-Xia; Ling, Zhi-Qiang; Hu, Fu-Jun; Sun, Yi-Ping; Zhang, Jing-Ye; Yang, Chen; Yang, Yi; Xiong, Yue; Guan, Kun-Liang; Ye, Dan

    2014-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway (PPP) and plays an essential role in the oxidative stress response by producing NADPH, the main intracellular reductant. G6PD deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide. Here, we show that G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. The K403 acetylated G6PD is incapable of forming active dimers and displays a complete loss of activity. Knockdown of G6PD sensitizes cells to oxidative stress, and re-expression of wild-type G6PD, but not the K403 acetylation mimetic mutant, rescues cells from oxidative injury. Moreover, we show that cells sense extracellular oxidative stimuli to decrease G6PD acetylation in a SIRT2-dependent manner. The SIRT2-mediated deacetylation and activation of G6PD stimulates PPP to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes. We also identified KAT9/ELP3 as a potential acetyltransferase of G6PD. Our study uncovers a previously unknown mechanism by which acetylation negatively regulates G6PD activity to maintain cellular NADPH homeostasis during oxidative stress. PMID:24769394

  14. Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model

    PubMed Central

    2013-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown. Methods HEM (human epidermal melanocyte) cells and human melanoma cells with the wild-type G6PD gene (A375-WT), G6PD deficiency (A375-G6PD∆), G6PD cDNA overexpression (A375-G6PD∆-G6PD-WT), and mutant G6PD cDNA (A375-G6PD∆-G6PD-G487A) were subcutaneously injected into 5 groups of nude mice. Expressions of G6PD, STAT3, STAT5, cell cycle-related proteins, and apoptotic proteins as well as mechanistic exploration of STAT3/STAT5 were determined by quantitative real-time PCR (qRT-PCR), immunohistochemistry and western blot. Results Delayed formation and slowed growth were apparent in A375-G6PD∆ cells, compared to A375-WT cells. Significantly decreased G6PD expression and activity were observed in tumor tissues induced by A375-G6PD∆, along with down-regulated cell cycle proteins cyclin D1, cyclin E, p53, and S100A4. Apoptosis-inhibited factors Bcl-2 and Bcl-xl were up-regulated; however, apoptosis factor Fas was down-regulated, compared to A375-WT cells. Moderate protein expressions were observed in A375-G6PD∆-G6PD-WT and A375-G6PD∆-G6PD-G487A cells. Conclusions G6PD may regulate apoptosis and expression of cell cycle-related proteins through phosphorylation of transcription factors STAT3 and STAT5, thus mediating formation and growth of human melanoma cells. Further study will, however, be required to determine potential clinical applications. PMID:23693134

  15. Correlation between oxidative stress and G6PD activity in neonatal jaundice.

    PubMed

    Raicevic, S; Eventov-Friedman, S; Bolevich, S; Selakovic, D; Joksimovic, J; Djuric, J; Globarevic-Vukcevic, G; Djuric, D; Jakovljevic, V

    2014-10-01

    Fetal distress represents a pathophysiological condition in which oxygen is not available to the fetus in sufficient quantities. In cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency, under conditions of oxidative stress, the residual G6PD and complimentary antioxidant mechanisms may become insufficient to neutralize the large amounts of ROS and to prevent severe hemolysis. Alteration in the oxidant-antioxidant profile is also known to occur in neonatal jaundice. The study group included 22 neonates presented with fetal distress during labor and 24 neonates with no evidence of fetal distress (control group). Umbilical cord blood samples were taken immediately after delivery, and the following blood tests were carried out after birth and at discharge from the hospital: erythrocyte count, total bilirubin, G6PD activity, and parameters presenting oxidative status [thiobarbituric acid reactive substances (TBARS), NO, O2 (-), H2O2, SOD, CAT, O2 (-)/SOD, and H2O2/CAT]. There were no significant differences in TBARS and NO values among neonates with or without fetal distress. However, the values of O2 (-), H2O2, SOD, O2 (-)/SOD, and H2O2/CAT among neonates born after fetal distress were significantly higher than in neonates without fetal distress (p < 0.01). In neonates with fetal distress, the total number of RBCs at delivery was significantly lower, accompanied with higher bilirubin content. Also neonates with fetal distress had lower activity of G6PD and lower CAT activity. Higher values of oxidative stress parameters in newborns delivered after fetal distress do not indicate strictly what occurred first-oxidative stress or basic lower G6PD activity.

  16. Association of G6PD with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia.

    PubMed

    Nouraie, Mehdi; Reading, Noel S; Campbell, Andrew; Minniti, Caterina P; Rana, Sohail R; Luchtman-Jones, Lori; Kato, Gregory J; Gladwin, Mark T; Castro, Oswaldo L; Prchal, Josef T; Gordeuk, Victor R

    2010-07-01

    The genetic bases of the highly variable degrees of anaemia and haemolysis in persons with Hb SS are not fully known, but several studies have indicated that G6PD deficiency is not a factor. The G6PD(202A) and G6PD(376G) alleles and alpha-thalassaemia were determined by molecular genetic testing in 261 children and adolescents with Hb SS in a multicentre study. G6PD(202A,376G) (G6PD A-) was defined as hemizygosity for both alleles in males and homozygosity in females. Among the participants 41% were receiving hydroxycarbamide. The prevalence of G6PD(202A,376G) was 13.6% in males and 3.3% in females with an overall prevalence of 8.7%. G6PD(202A,376G) was associated with a 10 g/l decrease in haemoglobin concentration (P = 0.008) but not with increased haemolysis as measured by lactate dehydrogenase, bilirubin, aspartate-aminotransferase, reticulocyte count or a haemolytic component derived from these markers (P > 0.09). Similar results were found within a sub-group of children who were not receiving hydroxycarbamide. By comparison, single and double alpha-globin deletions were associated with progressively higher haemoglobin concentrations (P = 0.005 for trend), progressively lower values for haemolytic component (P = 0.007), and increased severe pain episodes (P < 0.001). In conclusion, G6PD(202A,376G) may be associated with lower haemoglobin concentration in sickle cell anaemia by a mechanism other than increased haemolysis.

  17. G6PD haplotypes spanning Xq28 from F8C to red/green color vision

    SciTech Connect

    Filosa, S.; Lania, G.; Martini, G. ); Brancati, C.; Tagarelli, A. ); Calabro, V. Hammersmith Hospital, London ); Vulliamy, T.J.; Luzzatto, L. )

    1993-07-01

    The most telomeric region of the human X chromosome within band Xq28 consists of a gene-rich region of about 3 Mb which contains the genes for coagulation factor VIIIc, glucose-6-phosphate dehydrogenase (G6PD), and red/green color vision. The authors have studied five polymorphic sites from this region, in a sample of normal people from the Cosenza province of Southern Italy. These sites, which span a distance of some 350 kb, are in strong linkage disequilibrium. Of the 32 possible haplotypes only 10 were found, and 4 of these account for 80% of all X chromosomes analyzed. In addition, they found that all G6PD-deficient people with the G6PD Mediterranean mutation belong to only two haplotypes. One of these (Med 1) is found only within a small subregion of the area investigated, west of the Appennine mountain range. Most remarkably, all Med 1 G6PD-deficient individuals also had red/green color blindness. The more frequent haplotype (Med 2) is the same in Calabria and in Sardinia, where it accounts for about 90% of the G6PD Mediterranean mutations, despite the fact that gene flow between the populations of Sardinia and Southern Italy must have been limited. These data do not enable determination of whether the two types of G6PD Mediterranean have arisen through two separate identical mutational events or through a single mutational event followed by recombination. However, the data indicate relatively little recombination over an extended region of the X chromosome and they suggest that the G6PD Mediterranean mutation is recent by comparison to the other polymorphisms investigated. 44 refs., 4 figs., 5 tabs.

  18. Effective NET formation in neutrophils from individuals with G6PD Taiwan-Hakka is associated with enhanced NADP(+) biosynthesis.

    PubMed

    Cheng, M L; Ho, H Y; Lin, H Y; Lai, Y C; Chiu, D T Y

    2013-09-01

    In response to infection, neutrophils employ various strategies to defend against the invading microbes. One of such defense mechanisms is the formation of neutrophil extracellular traps (NETs). Recent studies suggest that reactive oxygen species is a signal critical to NET formation. This prompts us to examine whether neutrophils from individuals with glucose-6-phosphate dehydrogenase (G6PD) Taiwan-Hakka variant, which are prone to oxidative stress generation, have altered ability to form NET. We adopted an image-based method to study the NET formation potential in neutrophils from G6PD-deficient patients. Neutrophils from either normal or G6PD-deficient individuals underwent NETosis in response to phorbol 12-myristate 13-acetate (PMA). The extent of NETosis in the former did not significantly differ from that of the latter. Diphenyleneiodonium sulfate (DPI) and 3-methyladenine (MA) inhibited PMA-stimulated NET formation in these cells, suggesting the involvement of NADPH oxidase and autophagy in the process. Glucose oxidase (GO) and xanthine oxidase/xanthine (XO/X) could induce a similar extent of NET formation in normal and G6PD-deficient neutrophils. GO- or XO-induced NETosis was not inhibitable by MA, implying that reactive oxygen species (ROS) can act as an independent signal for activation of NETosis. Mechanistically, enhanced superoxide production in neutrophils was associated with increases in levels of NAD(+) and NADP(+), as well as activation of NAD(+) kinase. Taken together, these findings suggest that G6PD-deficient neutrophils are as equally efficient as normal cells in NET formation, and their deficiency in G6PD-associated NADPH regeneration capacity is largely compensated for by nicotinamide nucleotide biosynthesis.

  19. Acute haemolytic crisis due to concomitant presence of infection and possible altered acetaminophen catabolism in a Philipino child carrying the G6PD-Vanua Lava mutation.

    PubMed

    Minucci, Angelo; De Luca, Daniele; Torti, Eleonora; Concolino, Paola; Maurizi, Palma; Giardina, Bruno; Zuppi, Cecilia; Capoluongo, Ettore

    2011-05-01

    Glucose-6-phosphate dehydrogenase (G6PD), an X-linked hereditary deficiency, is the most common of all clinically significant enzyme defects. While many drugs are responsible for haemolytic anaemia in G6PD-deficient patients, acetaminophen's imputability is still under debate, although an overdose of this drug can provoke acute haemolytic events. We report a case of a Philipino child carrying the G6PD-Vanua Lava mutation with acute haemolytic crisis related to infection in progress and acetaminophen's administration. Fever and concomitant infection, through an increment of erythrocyte glutathione depletion, sensitized the infant to the haemolytic event. In this condition, acetaminophen (or paracetamol [PCM]) was capable of inducing a haemolytic crisis in our G6PD-deficient patient although administered under standard conditions. PCM seems to have induced the haemolytic event, probably by the alteration of its catabolism due to dehydration and fever. The enzymatic G6PD instability associated to the presence of the G6PD-Vanua Lava mutation could have led to an increment of red blood cells' sensitivity to lysis; hence, it is possible that PCM toxicity may also be due to the presence of this particular mutation. Finally, we propose a new biochemical classification of this G6PD variant.

  20. Increased Salivary Nitric Oxide and G6PD Activity in Refugees with Anxiety and Stress.

    PubMed

    Gammoh, Omar S; Al-Smadi, Ahmed; Al-Awaida, Wajdy; Badr, Mujtaba M; Qinna, Nidal A

    2016-10-01

    Anxiety and stress are related to physiological changes in humans. Accumulating evidence suggests a cross-talk between psychiatric disorders and oxidative stress. The objective of this study was to compare oxidative stress and defensive antioxidant biomarkers in a group of refugees with acute anxiety and stress with a group of local Jordanians. The Hamilton Anxiety Rating Scale (HAM-A) and the Perceived Stress Scale (PSS) Arabic version were used to assess anxiety and stress respectively. Salivary nitric oxide concentration, glucose-6-phosphate dehydrogenase (G6PD) activity and total salivary protein were compared. As expected, refugees showed higher anxiety and stress scores compared with Jordanians. Also, we report a significant increase in salivary nitric oxide and G6PD activity in the refugee group while total protein concentration did not vary between the two groups. This is the first study that demonstrates an increase in nitric oxide and G6PD activity in the saliva of refugees, thus highlighting their potential role as possible biomarkers in anxiety and stress disorders. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Red-cell GSH regeneration and glutathione reductase activity in G6PD variants in the Ferrara area.

    PubMed

    Anderson, B B; Carandina, G; Lucci, M; Perry, G M; Vullo, C

    1987-12-01

    Red-cell studies were carried out on three groups of G6PD-deficient subjects with different G6PD variants from the Ferrara area of Northern Italy. Red-cell GSH and activities of G6PD, glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured. A method was developed to measure red-cell GSH regeneration after oxidation of endogenous GSH in whole blood by diamide and only this clearly distinguished the variants from each other and from normal. Regeneration by 1 h was lowest in the Mediterranean variant, 0-10.2% in contrast to 93-98% in normal. A predisposition to a haemolytic crisis after ingestion of fava beans was not clearcut, but subjects appeared to be at risk if GSH regeneration at 1 h was less than 30% of the endogenous level, and red-cell FAD+ was very high indicated by high in vitro GR activity and inhibition by added FAD+. It is suggested that the most informative tests in G6PD deficiency are measurements of GSH regeneration in intact red cells plus GR activity and/or red-cell flavin compounds.

  2. Influence of dehydroepiandrosterone on G-6-PD activity and /sup 3/H-thymidine uptake of human lymphocytes in vitro

    SciTech Connect

    Ennas, M.G.; Laconi, S.; Dessi, S.; Milia, G.; Murru, M.R.; Manconi, P.E.

    1987-01-01

    Dehydroepiandrosterone (DHEA) was found to inhibit experimental cancer development in mouse and rat lung, colon and mammary gland. Since DHEA is a potent inhibitor of mammalian G-6-PD, the hypothesis that the compound could inhibit cell proliferation through an inhibition of the pentose phosphate pathway has been formulated. We studied the effects of DHEA on the proliferation in vitro of human lymphocytes induced by several mitogens (PHA, ConA and PWM), measuring /sup 3/H-thymidine uptake. DHEA inhibited /sup 3/H-thymidine uptake of mitogen-stimulated cells from both G-6-PD+ and G-6-PD- (mediterranean type deficiency) individuals in a dose-dependent and reversible fashion. The inhibitory effect was found even if DHEA was added to cells in the last hours of culture, simultaneously with the addition of /sup 3/H-thymidine. These data suggest that the inhibition of thymidine uptake induced by DHEA on human lymphocytes probably does not depend on the inhibition of G-6-PD.

  3. Glucose 6-phosphate dehydrogenase variants: a unique variant (G6PD Kobe) showed an extremely increased affinity for galactose 6-phosphate and a new variant (G6PD Sapporo) resembling G6PD Pea Ridge.

    PubMed

    Fujii, H; Miwa, S; Tani, K; Takegawa, S; Fujinami, N; Takahashi, K; Nakayama, S; Konno, M; Sato, T

    1981-01-01

    Two new glucose 6-phosphate dehydrogenase (G6PD) variants associated with chronic nonspherocytic hemolytic anemia were discovered, G6PD Kobe was found in a 16-year-old male associated with hemolytic crisis after upper respiratory infection. The enzyme activity of the variant was about 22% of that of the normal enzyme. The main enzymatic characteristics were slower than normal anodal electrophoretic mobility, high Km G6P, increased thermal-instability, an acidic pH optimum, and an extremely increased affinity for the substrate analogue, galactose 6-phosphate (Gal-6P). G6PD Sapporo was found in a 3-year-old male associated with drug-induced hemolysis. The enzyme activity was extremely low, being 3.6% of normal. In addition, this variant showed high Ki NADPH and thermal-instability. G6PD Kobe utilized the artificial substrate Gal-6P effectively as compared with the common natural substrate, glucose 6-phosphate. In G6PD Sapporo, NADPH could not exert the effect of product inhibition. The structural changes of these variants are expected to occur at the portions inducing conformational changes of the substrate binding site of the enzyme.

  4. A population survey of the glucose-6-phosphate dehydrogenase (G6PD) 563C>T (Mediterranean) mutation in Afghanistan.

    PubMed

    Jamornthanyawat, Natsuda; Awab, Ghulam R; Tanomsing, Naowarat; Pukrittayakamee, Sasithon; Yamin, Fazel; Dondorp, Arjen M; Day, Nicholas P J; White, Nicholas J; Woodrow, Charles J; Imwong, Mallika

    2014-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzyme defect and an important problem in areas with Plasmodium vivax infection because of the risk of haemolysis following administration of primaquine to treat the liver forms of the parasite. We undertook a genotypic survey of 713 male individuals across nine provinces of Afghanistan in which malaria is found, four in the north and five in the east. RFLP typing at nucleotide position 563 detected 40 individuals with the Mediterranean mutation 563C>T, an overall prevalence of 5.6%. This varied according to self-reported ethnicity, with prevalence in the Pashtun/Pashai group of 33/369 (8.9%) compared to 7/344 individuals in the rest of the population (2.0%; p<0.001, Chi-squared test). Multivariate analysis of ethnicity and geographical location indicated an adjusted odds ratio of 3.50 (95% CI 1.36-9.02) for the Pashtun/Pashai group, while location showed only a trend towards higher prevalence in eastern provinces (adjusted odds ratio = 1.73, 0.73-4.13). Testing of known polymorphic markers (1311C>T in exon 11, and C93T in intron XI) in a subset of 82 individuals wild-type at C563 revealed a mixture of 3 haplotypes in the background population and was consistent with data from the 1000 Genomes Project and published studies. By comparison individuals with G6PD deficiency showed a highly skewed haplotype distribution, with 95% showing the CT haplotype, a finding consistent with relatively recent appearance and positive selection of the Mediterranean variant in Afghanistan. Overall, the data confirm that the Mediterranean variant of G6PD is common in many ethnic groups in Afghanistan, indicating that screening for G6PD deficiency is required in all individuals before radical treatment of P. vivax with primaquine.

  5. A Population Survey of the Glucose-6-Phosphate Dehydrogenase (G6PD) 563C>T (Mediterranean) Mutation in Afghanistan

    PubMed Central

    Jamornthanyawat, Natsuda; Awab, Ghulam R.; Tanomsing, Naowarat; Pukrittayakamee, Sasithon; Yamin, Fazel; Dondorp, Arjen M.; Day, Nicholas P. J.; White, Nicholas J.; Woodrow, Charles J.; Imwong, Mallika

    2014-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzyme defect and an important problem in areas with Plasmodium vivax infection because of the risk of haemolysis following administration of primaquine to treat the liver forms of the parasite. We undertook a genotypic survey of 713 male individuals across nine provinces of Afghanistan in which malaria is found, four in the north and five in the east. RFLP typing at nucleotide position 563 detected 40 individuals with the Mediterranean mutation 563C>T, an overall prevalence of 5.6%. This varied according to self-reported ethnicity, with prevalence in the Pashtun/Pashai group of 33/369 (8.9%) compared to 7/344 individuals in the rest of the population (2.0%; p<0.001, Chi-squared test). Multivariate analysis of ethnicity and geographical location indicated an adjusted odds ratio of 3.50 (95% CI 1.36–9.02) for the Pashtun/Pashai group, while location showed only a trend towards higher prevalence in eastern provinces (adjusted odds ratio = 1.73, 0.73–4.13). Testing of known polymorphic markers (1311C>T in exon 11, and C93T in intron XI) in a subset of 82 individuals wild-type at C563 revealed a mixture of 3 haplotypes in the background population and was consistent with data from the 1000 Genomes Project and published studies. By comparison individuals with G6PD deficiency showed a highly skewed haplotype distribution, with 95% showing the CT haplotype, a finding consistent with relatively recent appearance and positive selection of the Mediterranean variant in Afghanistan. Overall, the data confirm that the Mediterranean variant of G6PD is common in many ethnic groups in Afghanistan, indicating that screening for G6PD deficiency is required in all individuals before radical treatment of P. vivax with primaquine. PMID:24586352

  6. HSPB1 Enhances SIRT2-Mediated G6PD Activation and Promotes Glioma Cell Proliferation

    PubMed Central

    Cao, Fei; Chen, Mantao; Zheng, Xiujue; Zhan, Renya

    2016-01-01

    Heat shock proteins belong to a conserved protein family and are involved in multiple cellular processes. Heat shock protein 27 (Hsp27), also known as heat HSPB1, participates in cellular responses to not only heat shock, but also oxidative or chemical stresses. However, the contribution of HSPB1 to anti-oxidative response remains unclear. Here, we show that HSPB1 activates G6PD in response to oxidative stress or DNA damage. HSPB1 enhances the binding between G6PD and SIRT2, leading to deacetylation and activation of G6PD. Besides, HSPB1 activates G6PD to sustain cellular NADPH and pentose production in glioma cells. High expression of HSPB1 correlates with poor survivalrate of glioma patients. Together, our study uncovers the molecular mechanism by which HSPB1 activates G6PD to protect cells from oxidative and DNA damage stress. PMID:27711253

  7. G6PD protects from oxidative damage and improves healthspan in mice

    PubMed Central

    Nóbrega-Pereira, Sandrina; Fernandez-Marcos, Pablo J.; Brioche, Thomas; Gomez-Cabrera, Mari Carmen; Salvador-Pascual, Andrea; Flores, Juana M.; Viña, Jose; Serrano, Manuel

    2016-01-01

    Reactive oxygen species (ROS) are constantly generated by cells and ROS-derived damage contributes to ageing. Protection against oxidative damage largely relies on the reductive power of NAPDH, whose levels are mostly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here, we report a transgenic mouse model with moderate overexpression of human G6PD under its endogenous promoter. Importantly, G6PD-Tg mice have higher levels of NADPH, lower levels of ROS-derived damage, and better protection from ageing-associated functional decline, including extended median lifespan in females. The G6PD transgene has no effect on tumour development, even after combining with various tumour-prone genetic alterations. We conclude that a modest increase in G6PD activity is beneficial for healthspan through increased NADPH levels and protection from the deleterious effects of ROS. PMID:26976705

  8. Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Zhang, Qiao; Yi, Xiaojia; Yang, Zhe; Han, Qiaoqiao; Di, Xuesong; Chen, Fufei; Wang, Yanling; Yi, Zihan; Kuang, Yingmin; Zhu, Yuechun

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) participates in glucose metabolism and it acts as the rate-limiting enzyme of the pentose phosphate pathway (PPP). Recently, G6PD dysregulation has been found in a variety of human cancers. Through analyzing published data in The Cancer Genome Atlas (TCGA), our pilot study indicated that G6PD mRNA expression was significantly higher in advanced Fuhrman grade in clear cell renal cell carcinoma (ccRCC). These clues promoted us to further evaluate the expression profile of G6PD and its prognostic impact in patients with ccRCC. In this study, G6PD expression levels were analyzed in 149 human ccRCC and normal tissues using immunohistochemistry. The results showed that compared with that in the normal renal samples, G6PD was found highly expressed in 51.0% of ccRCC (p<0.05). High expression of G6PD was significantly correlated to tumor extent, lymph node metastasis, Fuhrman grade, and TNM stage of ccRCC (all p<0.05). Moreover, positive G6PD expression was associated with poorer overall survival in ccRCC (p<0.001). In Cox regression analyses, high expression of G6PD also could be an independent prognostic factor for overall survival in ccRCC (p=0.007). This study suggests that overexpression of G6PD is associated with advanced disease status and therefore may become an important prognosticator for poor outcomes in ccRCC, as well as a potential therapeutic target for developing effective treatment modalities. PMID:28367246

  9. Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens

    PubMed Central

    Win, Htun Htun; Thitipanawan, Niramon; Po, Christina; Chowwiwat, Nongnud; Raksapraidee, Rattanaporn; Wilairisak, Pornpimon; Keereecharoen, Lily; Proux, Stéphane

    2017-01-01

    Background Radical cure of Plasmodium vivax malaria with 8-aminoquinolines (primaquine or tafenoquine) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD heterozygous females, because of individual variation in the pattern of X-chromosome inactivation (Lyonisation) in erythroid cells, may have low G6PD activity in the majority of their erythrocytes, yet are usually reported as G6PD “normal” by current phenotypic screening tests. Their haemolytic risk when treated with 8-aminoquinolines has not been well characterized. Methods and Findings In a cohort study nested within a randomised clinical trial that compared different treatment regimens for P. vivax malaria, patients with a normal standard NADPH fluorescent spot test result (≳30%–40% of normal G6PD activity) were randomised to receive 3 d of chloroquine or dihydroartemisinin-piperaquine in combination with primaquine, either the standard high dose of 0.5 mg base/kg/day for 14 d or a higher dose of 1 mg base/kg/d for 7 d. Patterns of haemolysis were compared between G6PD wild-type and G6PD heterozygous female participants. Between 21 February 2012 and 04 July 2014, 241 female participants were enrolled, of whom 34 were heterozygous for the G6PD Mahidol variant. Haemolysis was substantially greater and a larger proportion of participants reached the threshold of clinically significant haemolysis (fractional haematocrit reduction >25%) in G6PD heterozygotes taking the higher (7 d) primaquine dose (9/17 [53%]) compared with G6PD heterozygotes taking the standard high (14 d) dose (2/16 [13%]; p = 0.022). In heterozygotes, the mean fractional haematocrit reductions were correspondingly greater with the higher primaquine dose (7-d regimen): −20.4% (95% CI −26.0% to −14.8%) (nadir on day 5) compared with the standard high (14 d) dose: −13.1% (95% CI −17.6% to −8.6%) (nadir day 6). Two heterozygotes taking the higher (7 d) primaquine dose

  10. Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens.

    PubMed

    Chu, Cindy S; Bancone, Germana; Moore, Kerryn A; Win, Htun Htun; Thitipanawan, Niramon; Po, Christina; Chowwiwat, Nongnud; Raksapraidee, Rattanaporn; Wilairisak, Pornpimon; Phyo, Aung Pyae; Keereecharoen, Lily; Proux, Stéphane; Charunwatthana, Prakaykaew; Nosten, François; White, Nicholas J

    2017-02-01

    Radical cure of Plasmodium vivax malaria with 8-aminoquinolines (primaquine or tafenoquine) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD heterozygous females, because of individual variation in the pattern of X-chromosome inactivation (Lyonisation) in erythroid cells, may have low G6PD activity in the majority of their erythrocytes, yet are usually reported as G6PD "normal" by current phenotypic screening tests. Their haemolytic risk when treated with 8-aminoquinolines has not been well characterized. In a cohort study nested within a randomised clinical trial that compared different treatment regimens for P. vivax malaria, patients with a normal standard NADPH fluorescent spot test result (≳30%-40% of normal G6PD activity) were randomised to receive 3 d of chloroquine or dihydroartemisinin-piperaquine in combination with primaquine, either the standard high dose of 0.5 mg base/kg/day for 14 d or a higher dose of 1 mg base/kg/d for 7 d. Patterns of haemolysis were compared between G6PD wild-type and G6PD heterozygous female participants. Between 21 February 2012 and 04 July 2014, 241 female participants were enrolled, of whom 34 were heterozygous for the G6PD Mahidol variant. Haemolysis was substantially greater and a larger proportion of participants reached the threshold of clinically significant haemolysis (fractional haematocrit reduction >25%) in G6PD heterozygotes taking the higher (7 d) primaquine dose (9/17 [53%]) compared with G6PD heterozygotes taking the standard high (14 d) dose (2/16 [13%]; p = 0.022). In heterozygotes, the mean fractional haematocrit reductions were correspondingly greater with the higher primaquine dose (7-d regimen): -20.4% (95% CI -26.0% to -14.8%) (nadir on day 5) compared with the standard high (14 d) dose: -13.1% (95% CI -17.6% to -8.6%) (nadir day 6). Two heterozygotes taking the higher (7 d) primaquine dose required blood transfusion. In wild-type participants

  11. Implementation of G6PD testing and primaquine for P. vivax radical cure: Operational perspectives from Thailand and Cambodia.

    PubMed

    Kitchakarn, Suravadee; Lek, Dysoley; Thol, Sea; Hok, Chantheasy; Saejeng, Aungkana; Huy, Rekol; Chinanonwait, Nipon; Thimasarn, Krongthong; Wongsrichanalai, Chansuda

    2017-09-01

    Following progressive success in reducing the burden of malaria over the past two decades, countries of the Asia Pacific are now aiming for elimination of malaria by 2030. Plasmodium falciparum and Plasmodium vivax are the two main malaria species that are endemic in the region. P. vivax is generally perceived to be less severe but will be harder to eliminate, owing partly to its dormant liver stage (known as a hypnozoite) that can cause multiple relapses following an initial clinical episode caused by a mosquito-borne infection. Primaquine is the only anti-hypnozoite drug against P. vivax relapse currently available, with tafenoquine in the pipeline. However, both drugs may cause severe haemolysis in individuals with deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD), a hereditary defect. The overall incidence of malaria has significantly declined in both Thailand and Cambodia over the last 15 years. However, P. vivax has replaced P. falciparum as the dominant species in large parts of both countries. This paper presents the experience of the national malaria control programmes of the two countries, in their efforts to implement safe primaquine therapy for the radical cure, i.e. relapse prevention, of P. vivax malaria by introducing a rapid, point-of-care test to screen for G6PD deficiency.

  12. In silico evaluation of miRNA binding site in mutated 3'UTR mRNA of G6PD

    NASA Astrophysics Data System (ADS)

    Azmi, Syarifah Anis Wafa Binti Syed Mohd; Noorden, Mohd Shihabudin; Yusof, Nurul Yuziana Mohd; Ismail, Endom

    2015-09-01

    MicroRNAs (miRNAs) are small non coding RNA sized 21-25 nucleotide. It has the ability to bind to the 3'- untranslated regions (3'UTR) of their target genes. Consequently, the binding of miRNA in the 3'UTR of targeted mRNA will regulate the expression of this gene. Thus, changes in 3'UTR may affect miRNA binding to mRNA of their target gene, leading to aberrations in mRNA regulations or expression and likely contribute to the various phenotypic changes or clinical risk for certain diseases in man. Therefore, the aim of this study is to evaluate candidate miRNAs species involved during the regulation of glucose-6-phosphate dehydrogenase (G6PD) mRNA with and without a specific 3'UTR nucleotide change that was previously shown to be responsible for G6PD deficiency in a Negrito sub-group of the Malaysian Orang Asli. We have conducted in silico analysis using TargetScan, PITA, RegRNA 2.0 and miRanda platform. Our results indicate that three potential miRNAs may have a functional role towards the regulated expression of those bearing the 3'UTR mutation. The role of these eleven miRNA can be investigated in future in vitro expression studies in order to verify its miRNA:mRNA relationship.

  13. O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth

    PubMed Central

    Rao, Xiongjian; Duan, Xiaotao; Mao, Weimin; Li, Xuexia; Li, Zhonghua; Li, Qian; Zheng, Zhiguo; Xu, Haimiao; Chen, Min; Wang, Peng G.; Wang, Yingjie; Shen, Binghui; Yi, Wen

    2015-01-01

    The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. Upregulation of the PPP has been shown in several types of cancer. However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. Importantly, G6PD glycosylation is increased in human lung cancers. Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours. PMID:26399441

  14. Hepatitis B virus stimulates G6PD expression through HBx-mediated Nrf2 activation

    PubMed Central

    Liu, B; Fang, M; He, Z; Cui, D; Jia, S; Lin, X; Xu, X; Zhou, T; Liu, W

    2015-01-01

    Metabolic reprogramming is a hallmark of physiological changes in cancer. Cancer cells primarily apply glycolysis for cell metabolism, which enables the cells to use glycolytic intermediates for macromolecular biosynthesis in order to meet the needs of cell proliferation. Here, we show that glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway, is highly expressed in chronic hepatitis B virus (HBV)-infected human liver and HBV-associated liver cancer, together with an elevated activity of the transcription factor Nrf2. In hepatocytes, HBV stimulates by its X protein (HBx) the expression of G6PD in an Nrf2 activation-dependent pathway. HBx associates with the UBA and PB1 domains of the adaptor protein p62 and augments the interaction between p62 and the Nrf2 repressor Keap1 to form HBx–p62–Keap1 complex in the cytoplasm. The aggregation of HBx–p62–Keap1 complexes hijacks Keap1 from Nrf2 leading to the activation of Nrf2 and consequently G6PD transcription. Our data suggest that HBV upregulates G6PD expression by HBx-mediated activation of Nrf2. This implies a potential effect of HBV on the reprogramming of the glucose metabolism in hepatocytes, which may be of importance in the development of HBV-associated hepatocarcinoma. PMID:26583321

  15. Diversity in expression of glucose-6-phosphate dehydrogenase deficiency in females.

    PubMed

    Abdulrazzaq, Y M; Micallef, R; Qureshi, M; Dawodu, A; Ahmed, I; Khidr, A; Bastaki, S M; Al-Khayat, A; Bayoumi, R A

    1999-01-01

    The aims of this study were to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the United Arab Emirates (UAE), to describe the different mutations in the population, to determine its prevalence, and to study inheritance patterns in families of G6PD-deficient individuals. All infants born at Tawam Hospital, Al-Ain, UAE from January 1994 to September 1996 were screened at birth for their G6PD status. In addition, those attending well-baby clinics during the period were also screened for the disorder. Families of 40 known G6PD-deficient individuals, selected randomly from the records of three hospitals in the country, were assessed for G6PD deficiency. Where appropriate, this was followed by definition of G6PD mutations. Of 8198 infants, 746 (9.1%), comprising 15% of males and 5% of females tested, were found to be G6PD deficient. A total of 27 families were further assessed: of these, all but one family had the nt563 Mediterranean mutation. In one family, two individuals had the nt202 African mutation. The high manifestation of G6PD deficiency in women may be due to the preferential expression of the G6PD-deficient gene and X-inactivation of the normal gene, and/or to the presence of an 'enhancer' gene that makes the expression of the G6PD deficiency more likely. The high level of consanguinity which, theoretically, should result in a high proportion of homozygotes and consequently a higher proportion of females with the deficiency, was not found to be a significant factor.

  16. Glucose-6-phosphate dehydrogenase deficiency and risk of colorectal cancer in Northern Sardinia: A retrospective observational study.

    PubMed

    Dore, Maria P; Davoli, Agnese; Longo, Nunzio; Marras, Giuseppina; Pes, Giovanni M

    2016-11-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with a lower cancer risk, possibly via a reduction of mutagenic oxygen-free radicals and by reducing nicotinamide-adeninedinucleotide-phosphate for replicating cells. In Sardinia, the enzyme defect is frequent as a consequence of selection by malaria in the past. This study investigated the relationship between G6PD deficiency and colorectal cancer (CRC).A retrospective case-control study of 3901 patients from Sardinia, who underwent a colonoscopy between 2006 and 2016, was performed. G6PD phenotype was assessed for each subject. The proportion of pre and malignant colorectal lesions was compared in cases (G6PD-deficient) and controls (G6PD-normal). Data concerning age, sex, family history of CRC, smoking habits, body height, and weight, and also associated diseases were collected.The CRC risk reduction was 43.2% among G6PD-deficient compared with G6PD-normal subjects (odds ratio 0.57, 95% confidence interval 0.37-0.87, P = 0.010). Age, sex, family history of CRC, and also comorbidities such as type 1 diabetes and ischemic heart disease, were significantly associated with CRC risk. The protective effect of G6PD deficiency remained significant after adjusting for all covariates by logistic regression analysis, and was consistently lower across all age groups.Glucose-6-phosphate dehydrogenase enzyme deficiency is associated with a reduced risk of CRC.

  17. Triplo-X constitution of mother explains apparent occurrence of two recombinants in sibship segregating at two closely X-linked loci (G6PD and deutan).

    PubMed Central

    Rinaldi, A; Velivasakis, M; Latte, B; Filippi, G; Siniscalco, M

    1978-01-01

    Two male sibs believed to be examples of meiotic recombinants between the closely linked loci for G6PD deficiency of Mediterranean type and severe deutan color blindness proved to be simple segregants of a triplo-X mother of genotype d--GdMediterranean/d+GdMediterranean/d+GdB. This finding suggests that in Sardinia the linkage between the two loci under consideration may be tighter than previously assumed. PMID:309723

  18. Chemically Assisted Enucleation Results in Higher G6PD Expression in Early Bovine Female Embryos Obtained by Somatic Cell Nuclear Transfer

    PubMed Central

    Oliveira, Clara Slade; Tetzner, Tatiane Almeida Drummond; de Lima, Marina Ragagnin; de Melo, Danilas Salinet; Niciura, Simone Cristina Méo; Garcia, Joaquim Mansano

    2012-01-01

    Abstract Despite extensive efforts, low efficiency is still an issue in bovine somatic cell nuclear transfer (SCNT). The hypothesis of our study was that the use of cytoplasts produced by chemically assisted enucleation (EN) would improve nuclear reprogramming in nuclear transfer (NT)–derived embryos because it results in lower damage and higher cytoplasm content than conventional EN. For that purpose, we investigated the expression of two X-linked genes: X inactive-specific transcript (XIST) and glucose 6-phosphate dehydrogenase (G6PD). In the first experiment, gene expression was assessed in day-7 female blastocysts from embryonic cell NT (ECNT) groups [conventional, ECNT conv; chemically assisted, ECNT deme (demecolcine)]. Whereas in the ECNT conv group, only one embryo (25%; n=4) expressed XIST transcripts, most embryos showed XIST expression (75%; n=4) in the ECNT deme group. However, no significant differences in transcript abundance of XIST and G6PD were found when comparing the embryos from all groups. In a second experiment using somatic cells as nuclear donors, we evaluated gene expression profiles in female SCNT-derived embryos. No significant differences in relative abundance (RA) of XIST transcripts were observed among the groups. Nonetheless, higher (p<0.05) levels of G6PD were observed in SCNT deme and in vitro–derived groups in comparison to SCNT conv. To know whether higher G6PD expression in embryos derived from SCNT chemically assisted EN indicates higher metabolism in embryos considered of superior quality or if the presence of higher reactive oxygen species (ROS) levels generated by the increased oxygen consumption triggers G6PD activation, the expression of genes related to stress response should be investigated in embryos produced by that technique. PMID:22908977

  19. Knockdown of glucose-6-phosphate dehydrogenase (G6PD) following cerebral ischemic reperfusion: the pros and cons.

    PubMed

    Zhao, Gang; Zhao, Yanxin; Wang, Xingyu; Xu, Ying

    2012-07-01

    NADPH derived from glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, has been implicated not only to promote reduced glutathione (GSH) but also enhance oxidative stress in specific cellular conditions. In this study, the effects of G6PD antisense oligodeoxynucleotides (AS-ODNs) was examined on the CA1 pyramidal neurons following transient cerebral ischemia. Specifically knockdown of G6PD protein expression in hippocampus CA1 subregion at early reperfusion period (1-24 h) with a strategy to pre-treated G6PD AS-ODNs significantly reduced G6PD activity and NADPH level, an effect correlated with attenuation of NADPH oxidase activation and superoxide anion production. Concomitantly, pre-treatment of G6PD AS-ODNs markedly reduced oxidative DNA damage and the delayed neuronal cell death in rat hippocampal CA1 region induced by global cerebral ischemia. By contrast, knockdown of G6PD protein at late reperfusion period (48-96 h) increased oxidative DNA damage and exacerbated the ischemia-induced neuronal cell death in hippocampal CA1 region, an effect associated with reduced NADPH level and GSH/GSSG ratio. These findings indicate that G6PD not only plays a role in oxidative neuronal damage but also a neuroprotective role during different ischemic reperfusion period. Therefore, G6PD mediated oxidative response and redox regulation in the hippocampal CA1 act as the two sides of the same coin and may represent two potential applications of G6PD during different stage of cerebral ischemic reperfusion. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Comparison of quantitative and qualitative tests for glucose-6-phosphate dehydrogenase deficiency in the neonatal period.

    PubMed

    Keihanian, F; Basirjafari, S; Darbandi, B; Saeidinia, A; Jafroodi, M; Sharafi, R; Shakiba, M

    2017-06-01

    Considering the high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among newborns, different screening methods have been established in various countries. In this study, we aimed to assess the prevalence of G6PD deficiency among newborns in Rasht, Iran, and compare G6PD activity in cord blood samples, using quantitative and qualitative tests. This cross-sectional, prospective study was performed at five largest hospitals in Rasht, Guilan Province, Iran. The screening tests were performed for all the newborns, referred to these hospitals. Specimens were characterized in terms of G6PD activity under ultraviolet light, using the kinetic method and the qualitative fluorescent spot test (FST). We also determined the sensitivity, specificity, negative predictive value, and positive predictive value of the qualitative assay. Blood samples were collected from 1474 newborns. Overall, 757 (51.4%) subjects were male. As the findings revealed, 1376 (93.4%) newborns showed normal G6PD activity, while 98 (6.6%) had G6PD deficiency. There was a significant difference in the mean G6PD level between males and females (P = 0.0001). Also, a significant relationship was detected between FST results and the mean values obtained in the quantitative test (P < 0.0001). According to the present study, FST showed acceptable sensitivity and specificity for G6PD activity, although it appeared inefficient for diagnostic purposes in some cases. © 2017 John Wiley & Sons Ltd.

  1. Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Kaplan, M; Rubaltelli, F F; Hammerman, C; Vilei, M T; Leiter, C; Abramov, A; Muraca, M

    1996-05-01

    We used a system capable of measuring conjugated bilirubin and its monoconjugated and diconjugated fractions in serum to assess bilirubin conjugation in 29 glucose-6-phosphate dehydrogenase (G6PD)-deficient, term, male newborn infants and 35 control subjects; all had serum bilirubin levels > or = 256 mumol/L (15 mg/dI). The median value for diconjugated bilirubin was lower in the G6PD-deficient neonates than in control subjects (0.06 (range 0.00 to 1.84) vs 0.21 (range 0.00 to 1.02) mumol/L, p = 0.006). Diglucuronide was undetectable in 11 (38.9%) of the G6PD-deficient infants versus 3 (8.6%) of the control subjects (p = 0.015). These findings imply a partial defect of bilirubin conjugation not previously demonstrated in G6PD-deficient newborn infants.

  2. THE EFFECT OF WEEKLY STANDARD DOSES OF PRIMAQUINE AND CHLOROQUINE IN G6PD DEFICIENT CAUCASIANS

    DTIC Science & Technology

    vitro protection obtained by preincubating normal intact red cells with cysteine or cysteamine prior to the exposure of the cells to NEM, could possibly be ascribed to chemical reactions between the two compounds.

  3. AB104. Glucose-6 phospate dehydrogenase deficiency among mongolian neonates

    PubMed Central

    Batjargal, Khishigjargal; Nansal, Gerelmaa; Zagd, Gerelmaa; Ganbaatar, Erdenetuya

    2015-01-01

    Background and objective Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in humans, affecting 400 million people worldwide and a high prevalence in persons of African, Middle Asian countries. The most common clinical manifestations are neonatal jaundice and acute hemolytic anemia, which is caused by the impairment of erythrocyte’s ability to remove harmful oxidative stress triggered by exogenous agents such as drugs, infection, or fava bean ingestion. Neonatal hyperbilirubinemia caused by G6PD is strongly associated with mortality and long-term neurodevelopmental impairment. The study aims to determine a level of G6PD in healthy neonates. Methods We obtained blood spot samples from 268 infants around 24-72 hours in their age who has unsuspected intranatal and neonatal disorders. Glucose 6 phosphate dehydrogenase “Perkin Elmer, Finland” level is determined by Victor 2D Fluorometer assay, developing of neonatal jaundice is examined by recall. Results The76.5% of all participants (n=205) was assessed 4.36±1.15 Ug/Hb in normal reference range of G6PD, other 23.5% (n=63) was 0.96±0.51 Ug/Hb with G6PD deficiency. In the both sex, 51.5% of male 0.88±0.46 Ug/Hb (n=33) and 47.6% of female (n=30) 0.97±0.55 Ug/Hb was assessed with G6PD deficiency. Developing Jaundice period in number of 63 neonates with G6PD deficiency, 86% of neonates (n=54) was in 1-4 days, 4% of neonates (n=3) was in 5-7 days and there is no sign of jaundice in 9% (n=6). Therefore neonates with G6PD deficiency, 53.9% (n=34) continued jaundice more than two weeks. Conclusions G6PD deficiency was determined in male neonates (51.5%) more than female (47.6%). The 76.5% of all participants (n=205) was assessed 4.36±1.15 Ug/Hb in normal reference range of G6PDH other 23.5% (n=63) of all participants was 0.96±0.51 Ug/Hb with G6PD deficiency. It shows that G6PD might be one potential risk of neonatal jaundice and hyperbilirubinemia in neonates in Mongolia.

  4. X-linked glucose-6-phosphate dehydrogenase (G6PD) and autosomal 6-phosphogluconate dehydrogenase (6PGD) polymorphisms in baboons

    SciTech Connect

    VandeBerg, J.L.; Aivaliotis, M.J.; Samollow, P.B. )

    1992-12-01

    Electrophoretic polymorphisms of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were examined in captive colonies of five subspecies of baboons (Papio hamadryas). Phenotype frequencies and family data verified the X-linked inheritance of the G6PD polymorphism. Insufficient family data were available to confirm autosomal inheritance of the 6PGD polymorphism, but the electrophoretic patterns of variant types (putative heterozygotes) suggested the codominant expression of alleles at an autosomal locus. Implications of the G6PD polymorphism are discussed with regard to its utility as a marker system for research on X-chromosome inactivation during baboon development and for studies of clonal cell proliferation and/or cell selection during the development of atherosclerotic lesions in the baboon model. 61 refs., 1 fig., 4 tabs.

  5. Noninferiority of glucose-6-phosphate dehydrogenase deficiency diagnosis by a point-of-care rapid test vs the laboratory fluorescent spot test demonstrated by copper inhibition in normal human red blood cells.

    PubMed

    Baird, J Kevin; Dewi, Mewahyu; Subekti, Decy; Elyazar, Iqbal; Satyagraha, Ari W

    2015-06-01

    Tens of millions of patients diagnosed with vivax malaria cannot safely receive primaquine therapy against repeated attacks caused by activation of dormant liver stages called hypnozoites. Most of these patients lack access to screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency, a highly prevalent disorder causing serious acute hemolytic anemia with primaquine therapy. We optimized CuCl inhibition of G6PD in normal red blood cells (RBCs) to assess G6PD diagnostic technologies suited to point of care in the impoverished rural tropics. The most widely applied technology for G6PD screening-the fluorescent spot test (FST)-is impractical in that setting. We evaluated a new point-of-care G6PD screening kit (CareStart G6PD, CSG) against FST using graded CuCl treatments to simulate variable hemizygous states, and varying proportions of CuCl-treated RBC suspensions to simulate variable heterozygous states of G6PD deficiency. In experiments double-blinded to CuCl treatment, technicians reading FST and CSG test (n = 269) classified results as positive or negative for deficiency. At G6PD activity ≤40% of normal (n = 112), CSG test was not inferior to FST in detecting G6PD deficiency (P = 0.003), with 96% vs 90% (P = 0.19) sensitivity and 75% and 87% (P = 0.01) specificity, respectively. The CSG test costs less, requires no specialized equipment, laboratory skills, or cold chain for successful application, and performs as well as the FST standard of care for G6PD screening. Such a device may vastly expand access to primaquine therapy and aid in mitigating the very substantial burden of morbidity and mortality imposed by the hypnozoite reservoir of vivax malaria.

  6. Prevalence and molecular characterization of glucose-6-phosphate dehydrogenase deficiency in northern Thailand.

    PubMed

    Charoenkwan, Pimlak; Tantiprabha, Watcharee; Sirichotiyakul, Supatra; Phusua, Arunee; Sanguansermsri, Torpong

    2014-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common inherited enzymopathies in endemic areas of malaria including Southeast Asia. The molecular features of G6PD deficiency are similar among Southeast Asian population, with differences in the type of the prominent variants in each region. This study determined the prevalence and molecular characteristics of G6PD deficiency in northern Thailand. Quantitative assay of G6PD activity was conducted in 566 neonatal cord blood samples and 6 common G6PD mutations were determined by PCR-restriction fragment length polymorphism method on G6PD complete and intermediate deficiency samples. Ninety newborns had G6PD deficiency, with prevalence in male newborns of 17% and that of female newborns having an intermediate and complete deficiency of 13% and 2%, respectively. From 95 G6PD alleles tested, G6PD Mahidol, G6PD Kaiping, G6PD Canton, G6PD Viangchan, G6PD Union, and G6PD Chinese-5 was detected in 19, 17, 15, 13, 7, and 2 alleles, respectively. Our study shows that the prevalence of G6PD deficiency in northern Thai population is high and combination of the common Chinese mutations is the majority, a distribution different from central and southern Thailand where G6PD Viangchan is the prominent variant. These findings suggest a higher proportion of assimilated Chinese ethnic group in the northern Thai population.

  7. Glucose-6-phosphate dehydrogenase deficiency and risk of diabetes: a systematic review and meta-analysis.

    PubMed

    Lai, Yin Key; Lai, Nai Ming; Lee, Shaun Wen Huey

    2017-05-01

    Emerging epidemiological evidence suggests that patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may have a higher risk of developing diabetes. The aim of the review was to synthesise the evidence on the association between G6PD deficiency and diabetes. A systematic search on Medline, EMBASE, AMED and CENTRAL databases for studies published between January 1966 and September 2016 that assessed the association between G6PD deficiency and diabetes was conducted. This was supplemented by a review of the reference list of retrieved articles. We extracted data on study characteristics, outcomes and performed an assessment on the methodological quality of the studies. A random-effects model was used to compute the summary risk estimates. Fifteen relevant publications involving 949,260 participants were identified, from which seven studies contributed to the meta-analysis. G6PD deficiency was associated with a higher odd of diabetes (odds ratio 2.37, 95% confidence interval 1.50-3.73). The odds ratio of diabetes among men was higher (2.22, 1.31-3.75) compared to women (1.87, 1.12-3.12). This association was broadly consistent in the sensitivity analysis. Current evidence suggests that G6PD deficiency may be a risk factor for diabetes, with higher odds among men compared to women. Further research is needed to determine how G6PD deficiency moderates diabetes.

  8. Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the "old" and update of the new mutations.

    PubMed

    Minucci, Angelo; Moradkhani, Kamran; Hwang, Ming Jing; Zuppi, Cecilia; Giardina, Bruno; Capoluongo, Ettore

    2012-03-15

    In the present paper we have updated the G6PD mutations database, including all the last discovered G6PD genetic variants. We underline that the last database has been published by Vulliamy et al. [1] who analytically reported 140 G6PD mutations: along with Vulliamy's database, there are two main sites, such as http://202.120.189.88/mutdb/ and www.LOVD.nl/MR, where almost all G6PD mutations can be found. Compared to the previous mutation reports, in our paper we have included for each mutation some additional information, such as: the secondary structure and the enzyme 3D position involving by mutation, the creation or abolition of a restriction site (with the enzyme involved) and the conservation score associated with each amino acid position. The mutations reported in the present tab have been divided according to the gene's region involved (coding and non-coding) and mutations affecting the coding region in: single, multiple (at least with two bases involved) and deletion. We underline that for the listed mutations, reported in italic, literature doesn't provide all the biochemical or bio-molecular information or the research data. Finally, for the "old" mutations, we tried to verify features previously reported and, when subsequently modified, we updated the specific information using the latest literature data. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. The Effect of Ddt on the Polymorphism at the G6pd and Pgd Loci in DROSOPHILA MELANOGASTER

    PubMed Central

    Bijlsma, R.; Kerver, J. W. M.

    1983-01-01

    For the degradation of DDT and other chlorohydrocarbon insecticides energy in the form of NADPH is needed which for the greater part is supplied by the pentose phosphate shunt. Therefore the influence of DDT on the polymorphism at the G6pd and Pgd loci in Drosophila melanogaster was investigated by studying its effect on egg to adult survival and adult survival. The results show the existence of significant differences in fitness between the different genotypes of the two loci for both components. It is found that the effect of DDT supplementation differs significantly from the effect of sodium octanoate addition. DDT treatment also increases the activity of the pentose phosphate shunt as measured by the activity of G6PD and 6PGD. In larvae a 50% increase in activity is found and in adults a 100% increase. As there is little doubt that the activities of G6PD and 6PGD are somehow correlated with the fitness of flies, the data are discussed in relation to the in vitro and in vivo differences in activity between the different allozymes of both G6PD and 6PGD. PMID:6404694

  10. Incidence and molecular characterization of Glucose-6-Phosphate Dehydrogenase deficiency among neonates for newborn screening in Chaozhou, China.

    PubMed

    Yang, H; Wang, Q; Zheng, L; Zhan, X-F; Lin, M; Lin, F; Tong, X; Luo, Z-Y; Huang, Y; Yang, L-Y

    2015-06-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in southern China. The aim of this study is to assess the extent of this disease in Chinese neonates and determine its molecular characteristics using a novel molecular screening method. A total of 2500 neonates were routinely screened for G6PD deficiency using a modified fluorescent spot test (FST). PCR-high-resolution melting (HRM) analysis was then used for the molecular assay. The overall incidence of G6PD deficiency was 2.68% in our study cohort. Frequency in male population was 3.22% (44 neonates of 1365 male neonates), and in female population was 2.03% (23 neonates of 1135 female neonates). Of the 67 newborns suspected to be G6PD deficient based on FST (44 males, 23 females), 58 of 67 (87%) were detected with gene alterations. Seven kinds of mutations [c.95A>G, c.392G>T, c.493A>G, c.871G>A, c.1360C>T, c.1376G>T, and c.1388G>A] were identified by HRM analysis. Routine newborn screening in Chaozhou, China with a relatively high prevalence of G6PD deficiency is justified and meets the World Health Organization recommendation. The usage of molecular diagnosis can favor the detection of heterozygotes which can be a supplement to regular newborn screening and useful for premarital and prenatal diagnosis for G6PD deficiency. © 2014 John Wiley & Sons Ltd.

  11. [Glucose-6-phosphate dehydrogenase deficiency in Japan].

    PubMed

    Kanno, Hitoshi; Ogura, Hiromi

    2015-07-01

    In the past 10 years, we have diagnosed congenital hemolytic anemia in 294 patients, approximately 33% of whom were found to have glucose-6-phosphate dehydrogenase (G6PD) deficiency. It is becoming more common for Japanese to marry people of other ethnic origins, such that G6PD deficiency is becoming more prevalent in Japan. Japanese G6PD deficiency tends to be diagnosed in the neonatal period due to severe jaundice, while G6PD-deficient patients with foreign ancestors tend to be diagnosed at the onset of an acute hemolytic crisis before the age of six. It is difficult to predict the clinical course of each patient by G6PD activity, reduced glutathione content, or the presence/absence of severe neonatal jaundice. We propose that both neonatal G6PD screening and systematic analyses of G6PD gene mutations may be useful for personalized management of patients with G6PD-deficient hemolytic anemia.

  12. ATM/G6PD-driven redox metabolism promotes FLT3 inhibitor resistance in acute myeloid leukemia

    PubMed Central

    D’Alessandro, Angelo; Alvarez-Calderon, Francesca; Kim, Jihye; Nemkov, Travis; Adane, Biniam; Rozhok, Andrii I.; Kumar, Amit; Kumar, Vijay; Pollyea, Daniel A.; Wempe, Michael F.; Jordan, Craig T.; Serkova, Natalie J.; Tan, Aik Choon; Hansen, Kirk C.; DeGregori, James

    2016-01-01

    Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are common in acute myeloid leukemia (AML) and drive leukemic cell growth and survival. Although FLT3 inhibitors have shown considerable promise for the treatment of AML, they ultimately fail to achieve long-term remissions as monotherapy. To identify genetic targets that can sensitize AML cells to killing by FLT3 inhibitors, we performed a genome-wide RNA interference (RNAi)-based screen that identified ATM (ataxia telangiectasia mutated) as being synthetic lethal with FLT3 inhibitor therapy. We found that inactivating ATM or its downstream effector glucose 6-phosphate dehydrogenase (G6PD) sensitizes AML cells to FLT3 inhibitor induced apoptosis. Examination of the cellular metabolome showed that FLT3 inhibition by itself causes profound alterations in central carbon metabolism, resulting in impaired production of the antioxidant factor glutathione, which was further impaired by ATM or G6PD inactivation. Moreover, FLT3 inhibition elicited severe mitochondrial oxidative stress that is causative in apoptosis and is exacerbated by ATM/G6PD inhibition. The use of an agent that intensifies mitochondrial oxidative stress in combination with a FLT3 inhibitor augmented elimination of AML cells in vitro and in vivo, revealing a therapeutic strategy for the improved treatment of FLT3 mutated AML. PMID:27791036

  13. Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

    PubMed

    Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

    2015-01-01

    Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is

  14. Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana – A Cohort Study

    PubMed Central

    Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

    2015-01-01

    Background Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Methods and Findings Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. Conclusions There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin

  15. A C {r_arrow} T transition at nucleotide 592 accounts for the most frequent mutation of G6PD gene in Taiwanese aboriginal Ami tribe: detection by mutagenically separated PCR (MS-PCR)

    SciTech Connect

    Lin, S.P.; Sun, W.; Chang, J.G.

    1994-09-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest known enzymopathy in Taiwan. It is estimated to affect 3% of our population, and its molecular defects have been characterized recently. There are 9 point mutations identified with a C {r_arrow} T substitution at nucleotide (nt) 592 in exon VI, the least frequently seen (0.8%) of all mutations. To characterize mutations of the G6PD gene in the Ami people, the most populous of Taiwanese minorities, we studied 21 G6PD-deficient Ami infants and their family members. Natural and amplification-created restriction sites were generated by PCR technique with 10 pairs of primers applied for the screening. By studying the first 7 cases, we found an identical C {r_arrow} T transition at nt 592. MS-PCR was then designed to rapidly detect the nt 592 mutation. As a result, 17 infants are disclosed as having the C {r_arrow} T transition at nt 592, and 2 have a G {r_arrow} T substitution at nt 1376, which were finally verified to be derived from a Chinese Min-Nan ancestor. The genetic defect of the remaining 2 infants remains unidentified. This study has shown that MS-PCR is a feasible and highly sensitive technique for screening mutation carriers in pooled DNA samples. The homogeneity of the nt 592 mutation in the Ami people has proved to be a good indicator for anthropological research.

  16. Sub-Saharan red cell antigen phenotypes and glucose-6-phosphate dehydrogenase deficiency variants in French Guiana.

    PubMed

    Petit, Florence; Bailly, Pascal; Chiaroni, Jacques; Mazières, Stéphane

    2016-06-07

    The treatment of Plasmodium vivax infections requires the use of primaquine, which can lead to severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. However, most of the Latin American countries, which are still endemic for vivax malaria, lack information on the distribution of G6PD deficiency (G6PDd). No survey has been performed so far in French Guiana. Herein, 80 individuals of the French Guianan Noir Marron population were scrutinized for red cell surface antigens of six blood group systems (ABO, Rh, Kell, Kidd, Duffy and MNS) and G6PD genetic polymorphisms. First, the sub-Saharan origin of the red cell phenotypes was assessed in relation with the literature. Then, given that the main sub-Saharan G6PDd variants are expected to be encountered, only the G6PD sequences of exons 4, 5, 6 and 9 were screened. This work aims at appraising the G6PD gene variation in this population, and thus, contributing to the G6PD piecemeal information in Latin America. Ninety-seven percent (97 %) of the red cells are Fy(a- b-), either D+ C- E- c+ e+ or D+ C+ E- c+ e+ and 44 % exhibited the Fya-/Jkb-/S- combined phenotype. Noteworthy is the detection of the G6PD(Val68Met) variant characterized by c.202G > A transition, G6PD(Asn126Asp) variant characterized by c.376A>G transition and G6PD(Asp181Val) variant characterized by c.542A>T transversion of the G6PD gene in 22.5 % of the sample, characteristic of the A(-(202)), A and Santamaria G6PDd variants, respectively. French Guianan Noir Marron population represents a pool of Rh-D antigen positive, Duffy-negative and G6PD-deficient erythrocytes, the latter accounting for one in every eight persons. The present study provides the first community-based estimation of the frequency of G6PDd polymorphisms in French Guiana. These results contribute to the G6PD genetic background information puzzle in Latin America.

  17. Overexpression of G6PD and HSP90 Beta in Mice with Benzene Exposure Revealed by Serum Peptidome Analysis.

    PubMed

    Zhang, Juan; Tan, Kehong; Meng, Xing; Yang, Wenwen; Wei, Haiyan; Sun, Rongli; Yin, Lihong; Pu, Yuepu

    2015-09-10

    The small peptides representation of the original proteins are a valuable source of information that can be used as biomarkers involved in toxicity mechanism for chemical exposure. The aim of this study is to investigate serum peptide biomarkers of benzene exposure. C57BL/6 mice were enrolled into control group and benzene groups of 150 and 300 mg/kg/d Serum peptides were identified by mass spectrometry using an assisted laser desorption ionization/time of flight mass spectrometry (MS). Differential peptide spectra were obtained by tandem mass spectrometry and analyzed by searching the International Protein Index using the Sequest program. Forty-one peptide peaks were found in the range of 1000-10,000 Da molecular weight. Among them, seven peaks showed significantly different expression between exposure groups and control group. Two peptide peaks (1231.2 and 1241.8), which showed a two-fold increase in expression, were sequenced and confirmed as glucose 6-phosphate dehydrogenase (G6PD) and heat shock protein 90 Beta (HSP90 Beta), respectively. Furthermore, the expression of the two proteins in liver cells showed the same trend as in serum. In conclusion, G6PD and HSP90 beta might be the candidate serum biomarkers of benzene exposure. It also provided possible clues for the molecular mechanism of benzene-induced oxidative stress.

  18. Overexpression of G6PD and HSP90 Beta in Mice with Benzene Exposure Revealed by Serum Peptidome Analysis

    PubMed Central

    Zhang, Juan; Tan, Kehong; Meng, Xing; Yang, Wenwen; Wei, Haiyan; Sun, Rongli; Yin, Lihong; Pu, Yuepu

    2015-01-01

    The small peptides representation of the original proteins are a valuable source of information that can be used as biomarkers involved in toxicity mechanism for chemical exposure. The aim of this study is to investigate serum peptide biomarkers of benzene exposure. C57BL/6 mice were enrolled into control group and benzene groups of 150 and 300 mg/kg/d Serum peptides were identified by mass spectrometry using an assisted laser desorption ionization/time of flight mass spectrometry (MS). Differential peptide spectra were obtained by tandem mass spectrometry and analyzed by searching the International Protein Index using the Sequest program. Forty-one peptide peaks were found in the range of 1000–10,000 Da molecular weight. Among them, seven peaks showed significantly different expression between exposure groups and control group. Two peptide peaks (1231.2 and 1241.8), which showed a two-fold increase in expression, were sequenced and confirmed as glucose 6-phosphate dehydrogenase (G6PD) and heat shock protein 90 Beta (HSP90 Beta), respectively. Furthermore, the expression of the two proteins in liver cells showed the same trend as in serum. In conclusion, G6PD and HSP90 beta might be the candidate serum biomarkers of benzene exposure. It also provided possible clues for the molecular mechanism of benzene-induced oxidative stress. PMID:26378550

  19. miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD

    PubMed Central

    Liu, Guang-Cai; Hong, Ying; Chen, Hong-Lan; Kong, Shu-Yi; Huang, Yan-Mei; Xiyang, Yan-Bin; Jin, Hua

    2016-01-01

    Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3′-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate. PMID:27861141

  20. miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD.

    PubMed

    Hu, Tao; Chang, Ye-Fei; Xiao, Zhangang; Mao, Rui; Tong, Jun; Chen, Bo; Liu, Guang-Cai; Hong, Ying; Chen, Hong-Lan; Kong, Shu-Yi; Huang, Yan-Mei; Xiyang, Yan-Bin; Jin, Hua

    2016-12-27

    Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3'-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate.

  1. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study

    PubMed Central

    Uyoga, Sophie; Ndila, Carolyne M; Macharia, Alex W; Nyutu, Gideon; Shah, Shivang; Peshu, Norbert; Clarke, Geraldine M; Kwiatkowski, Dominic P; Rockett, Kirk A; Williams, Thomas N

    2015-01-01

    Summary Background The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. Methods We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3–12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. Findings 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant

  2. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study.

    PubMed

    Uyoga, Sophie; Ndila, Carolyne M; Macharia, Alex W; Nyutu, Gideon; Shah, Shivang; Peshu, Norbert; Clarke, Geraldine M; Kwiatkowski, Dominic P; Rockett, Kirk A; Williams, Thomas N

    2015-10-01

    The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3-12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR

  3. Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity.

    PubMed

    Rochford, Rosemary; Ohrt, Colin; Baresel, Paul C; Campo, Brice; Sampath, Aruna; Magill, Alan J; Tekwani, Babu L; Walker, Larry A

    2013-10-22

    Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.

  4. Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity

    PubMed Central

    Rochford, Rosemary; Ohrt, Colin; Baresel, Paul C.; Campo, Brice; Sampath, Aruna; Magill, Alan J.; Tekwani, Babu L.; Walker, Larry A.

    2013-01-01

    Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations. PMID:24101478

  5. Dissimilar Deficiency of Glucose-6-Phosphate Dehydrogenase (G-6-PD) among the AFARS and the Somalis of Djibouti

    DTIC Science & Technology

    1991-01-01

    ET LES SOMALIS DE DJIBOUI I and/or par W. SIDRAK (1), E. FOX (2), D. POLYCARPE ( 3 ), J.G. OLSON ( 4 ) S.0. SHAKIB (5), J.P. PARRA (6), G. RODIER (7...Baltimore. ( 3 ) Docteur en midecine. Service midical inter-entreprses (SMI-1), Djibouti. ( 4 ) Docteur en philosophic (PhD), Head, Division of...hommes d’origine* phosphate deshvdrogdnase en Italie ( 4 ). Somali. La part relative de l’accis palustre et du dificit en La description relativement

  6. Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis

    PubMed Central

    Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Titouna, Afaf; Elmaraezy, Ahmed; Trang, Nguyen Thi Huyen; Phuoc Long, Nguyen; Hoang Anh, Nguyen; Diem Nghi, Tran; The Hung, Bui; Van Hieu, Mai; Ky Anh, Nguyen; Huy, Nguyen Tien; Hirayama, Kenji

    2017-01-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59–1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40–0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96–1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57–0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46–1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61–1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender. PMID:28382932

  7. Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

    PubMed

    Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Titouna, Afaf; Elmaraezy, Ahmed; Trang, Nguyen Thi Huyen; Phuoc Long, Nguyen; Hoang Anh, Nguyen; Diem Nghi, Tran; The Hung, Bui; Van Hieu, Mai; Ky Anh, Nguyen; Huy, Nguyen Tien; Hirayama, Kenji

    2017-04-06

    Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59-1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40-0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96-1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57-0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46-1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61-1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender.

  8. Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency

    PubMed Central

    Lee, Jaewoong; Choi, Hayoung; Kim, Jiyeon; Kwon, Ahlm; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Lee, Jae Wook; Chung, Nack-Gyun

    2017-01-01

    Background We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. Methods In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. Results One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. Conclusions The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability. PMID:28028996

  9. Pyruvate kinase deficiency

    MedlinePlus

    ... the second most common cause, after glucose-6-phosphate dehydrogenase (G6PD) deficiency . PKD is found in people ... Read More Anemia Autosomal recessive Enzyme Glucose-6-phosphate dehydrogenase deficiency Hemolytic anemia Review Date 10/27/ ...

  10. Integrative gene expression profiling reveals G6PD-mediated resistance to RNA-directed nucleoside analogues in B-cell neoplasms.

    PubMed

    McBrayer, Samuel K; Yarrington, Michael; Qian, Jun; Feng, Gang; Shanmugam, Mala; Gandhi, Varsha; Krett, Nancy L; Rosen, Steven T

    2012-01-01

    The nucleoside analogues 8-amino-adenosine and 8-chloro-adenosine have been investigated in the context of B-lineage lymphoid malignancies by our laboratories due to the selective cytotoxicity they exhibit toward multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL) cell lines and primary cells. Encouraging pharmacokinetic and pharmacodynamic properties of 8-chloro-adenosine being documented in an ongoing Phase I trial in CLL provide additional impetus for the study of these promising drugs. In order to foster a deeper understanding of the commonalities between their mechanisms of action and gain insight into specific patient cohorts positioned to achieve maximal benefit from treatment, we devised a novel two-tiered chemoinformatic screen to identify molecular determinants of responsiveness to these compounds. This screen entailed: 1) the elucidation of gene expression patterns highly associated with the anti-tumor activity of 8-chloro-adenosine in the NCI-60 cell line panel, 2) characterization of altered transcript abundances between paired MM and MCL cell lines exhibiting differential susceptibility to 8-amino-adenosine, and 3) integration of the resulting datasets. This approach generated a signature of seven unique genes including G6PD which encodes the rate-determining enzyme of the pentose phosphate pathway (PPP), glucose-6-phosphate dehydrogenase. Bioinformatic analysis of primary cell gene expression data demonstrated that G6PD is frequently overexpressed in MM and CLL, highlighting the potential clinical implications of this finding. Utilizing the paired sensitive and resistant MM and MCL cell lines as a model system, we go on to demonstrate through loss-of-function and gain-of-function studies that elevated G6PD expression is necessary to maintain resistance to 8-amino- and 8-chloro-adenosine but insufficient to induce de novo resistance in sensitive cells. Taken together, these results indicate that G6PD activity

  11. Glucose-6-phosphate dehydrogenase deficiency prevalence and genetic variants in malaria endemic areas of Colombia.

    PubMed

    Valencia, Sócrates Herrera; Ocampo, Iván Darío; Arce-Plata, María Isabel; Recht, Judith; Arévalo-Herrera, Myriam

    2016-05-26

    Glucose 6-phosphate dehydrogenase (G6PD) is an enzyme involved in prevention of cellular oxidative damage, particularly protecting erythrocytes from haemolysis. An estimated 400 million people present variable degrees of inherited G6PD deficiency (G6PDd) which puts them at risk for developing haemolysis triggered by several risk factors including multiple drugs and certain foods. Primaquine (PQ) is a widely used anti-malarial drug that can trigger haemolysis in individuals with G6PDd. Intensification of malaria control programmes worldwide and particularly malaria elimination planning in some regions recommend a more extensive use of PQ and related drugs in populations with different G6PDd prevalence. This a preliminary study to assess the prevalence of G6PDd in representative malaria endemic areas of Colombia by measuring G6PD phonotype and genotypes. Volunteers (n = 426) from four malaria endemic areas in Colombia (Buenaventura, Tumaco, Tierralta and Quibdo) were enrolled. Blood samples were drawn to evaluate G6PD enzymatic activity by using a quantitative G6PD test and a subset of samples was analysed by PCR-RFLP to determine the frequency of the three most common G6PD genotypic variants: A-, A+ and Mediterranean. A total of 28 individuals (6.56 %) displayed either severe or intermediate G6PDd. The highest prevalence (3.51 %) was in Buenaventura, whereas G6PDd prevalence was lower (<1 %) in Tierralta and Quibdo. G6PD A alleles were the most frequent (15.23 %) particularly in Buenaventura and Tumaco. Overall, a high frequency of G6PD A- genotype, followed by A+ genotype was found in the analysed population. G6PDd based on enzymatic activity as well as G6PD A allelic variants were found in malaria-endemic populations on the Pacific coast of Colombia, where most of malaria cases are caused by Plasmodium vivax infections. These infections are treated for 14 days with PQ, however there are no official reports of PQ-induced haemolytic crises. Further

  12. Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria

    PubMed Central

    2012-01-01

    Background Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children <5 years of age with uncomplicated malaria. Methods This case–control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop ≥2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model. Results G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p = 0.56). The risk of a Hb drop ≥2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p = 0.76) or CDA treatment (AOR: 1.28; p = 0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p = 0.25) of experiencing a Hb drop ≥2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G

  13. Glucose-6-Phosphate Dehydrogenase Deficiency.

    PubMed

    Luzzatto, Lucio; Nannelli, Caterina; Notaro, Rosario

    2016-04-01

    G6PD is a housekeeping gene expressed in all cells. Glucose-6-phosphate dehydrogenase (G6PD) is part of the pentose phosphate pathway, and its main physiologic role is to provide NADPH. G6PD deficiency, one of the commonest inherited enzyme abnormalities in humans, arises through one of many possible mutations, most of which reduce the stability of the enzyme and its level as red cells age. G6PD-deficient persons are mostly asymptomatic, but they can develop severe jaundice during the neonatal period and acute hemolytic anemia when they ingest fava beans or when they are exposed to certain infections or drugs. G6PD deficiency is a global health issue.

  14. Effects of iron chloride/zeolıte on G6PD of rainbow trout (Oncorhynchus mykiss)'s liver tissue

    NASA Astrophysics Data System (ADS)

    Alak, Gonca; Uçar, Arzu; Parlak, Veysel; Kocaman, Esat Mahmut; Atamanalp, Muhammed

    2016-04-01

    Aquatic ecosystems have been negatively affected by the contamination of ground and surface waters as a result of various activities. Due to the ferrous chloride (FeCl2), which is used as the reducing agent for the organic synthesis reactions in the contamination of water column and sediment, iron salts may be very toxic for some aquatic organisms. In order to minimize these effects, natural products such as zeolite have been widely used in recently years. For this reason, rainbow trout were exposed to FeCl2 and/or zeolite ((FeCl2 (0.002 mg/l)(A), FeCl2+zeolite (0.002 mg/l+1 gr/l) (B), zeolite (1 gr/l) (C) and control (without FeCl2 and/or zeolite (D)). for 28 days and their oxidative stress responses were investigated. At the end of the treatment period, Glucose-6- phosphate dehydrogenase (G6PD) activity was determined in the samples taken from livers. G6PD values for liver tissues were found statistically important in the control and treatment groups (p<0.01).

  15. Historical Selection, Amino Acid Polymorphism and Lineage-Specific Divergence at the G6pd Locus in Drosophila Melanogaster and D. Simulans

    PubMed Central

    Eanes, W. F.; Kirchner, M.; Yoon, J.; Biermann, C. H.; Wang, I. N.; McCartney, M. A.; Verrelli, B. C.

    1996-01-01

    The nucleotide diversity across 1705 bp of the G6pd gene is studied in 50 Drosophila melanogaster and 12 D. simulans lines. Our earlier report contrasted intraspecific polymorphism and interspecific differences at silent and replacement sites in these species. This report expands the number of European and African lines and examines the pattern of polymorphism with respect to the common A/B allozymes. In D. melanogaster the silent nucleotide diversity varies 2.8-fold across localities. The B allele sequences are two- to fourfold more variable than the derived A allele, and differences between allozymes are twice as among B alleles. There is strong linkage disequilibrium across the G6pd region. In both species the level of silent polymorphism increases from the 5' to 3' ends, while there is no comparable pattern in level of silent site divergence or fixation. The neutral model is not rejected in either species. Using D. yakuba as an outgroup, the D. melanogaster lineage shows a twofold greater rate of silent fixation, but less than half the rate of amino acid replacement. Lineage-specific differences in mutation fixation are inconsistent with neutral expectations and suggest the interaction of species-specific population size differences with both weakly advantageous and deleterious selection. PMID:8913747

  16. Detection of Occult Acute Kidney Injury in Glucose-6-Phosphate Dehydrogenase Deficiency Anemia

    PubMed Central

    Abdel Hakeem, Gehan Lotfy; Abdel Naeem, Emad Allam; Swelam, Salwa Hussein; El Morsi Aboul Fotoh, Laila; El Mazary, Abdel Azeem Mohamed; Abdel Fadil, Ashraf Mohamed; Abdel Hafez, Asmaa Hosny

    2016-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency anemia is associated with intravascular hemolysis. The freely filtered hemoglobin can damage the kidney. We aimed to assess any subclinical renal injury in G6PD children. Methods Sixty children were included. Thirty G6PD deficiency anemia children were enrolled during the acute hemolytic crisis and after the hemolytic episode had elapsed. Another thirty healthy children were included as controls. Serum cystatin C, creatinine levels, and urinary albumin/creatinine (A/C) ratio were measured, and the glomerular filtration rate (GFR) was calculated. Results Significantly higher urinary A/C ratio (p=0.001,0.002 respectively) and lower GFR (p=0.001 for both) were found during hemolysis and after the hemolytic episode compared to the controls. Also, significant higher serum cystatin C (p=0.001), creatinine (p=0.05) and A/C (p= 0.001) ratio and insignificant lower GFR (p=0.3) during acute hemolytic crisis compared to the same children after the hemolytic episode subsided. Conclusions G6PD deficiency anemia is associated with a variable degree of acute renal injury during acute hemolytic episodes which may persist after elapsing of the hemolytic crises. PMID:27648201

  17. Should we screen newborns for glucose-6-phosphate dehydrogenase deficiency in the United States?

    PubMed

    Watchko, J F; Kaplan, M; Stark, A R; Stevenson, D K; Bhutani, V K

    2013-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common X-linked enzymopathy can lead to severe hyperbilirubinemia, acute bilirubin encephalopathy and kernicterus in the United States. Neonatal testing for G6PD deficiency is not yet routine and the American Academy of Pediatrics recommends testing only in jaundiced newborns who are receiving phototherapy whose family history, ethnicity, or geographic origin suggest risk for the condition, or for infants whose response to phototherapy is poor. Screening tests for G6PD deficiency are available, are suitable for use in newborns and have been used in birth hospitals. However, US birth hospitals experience is limited and no national consensus has emerged regarding the need for newborn G6PD testing, its effectiveness or the best approach. Our review of current state of G6PD deficiency screening highlights research gaps and informs specific operational challenges to implement universal newborn G6PD testing concurrent to bilirubin screening in the United States.

  18. Pulse-field linkage of the P3, G6pd and Cf-8 genes on the mouse X chromosome: demonstration of synteny at the physical level.

    PubMed Central

    Brockdorff, N; Amar, L C; Brown, S D

    1989-01-01

    Utilising pulse-field gel electrophoresis physical linkage between three mouse X-linked genes has been demonstrated. The three genes, P3, G6pd and Cf-8 all lie within 400 Kb of DNA. This physical linkage mirrors the situation on the human X chromosome, representing the first demonstration of mouse/human synteny at the physical level. A detailed physical map encompassing 1.6 Mbp of this region is presented. A number of the rare cutter restriction enzyme sites within this map are partially blocked on the inactive X chromosome, presumably due to the methylation of CpG rich islands. Pulsed field gel electrophoresis therefore provides a useful tool for the study of X-inactivation over large regions of the X chromosome. Images PMID:2922282

  19. Construction of a transcription map of a 300 kb region around the human G6PD locus by direct cDNA selection.

    PubMed

    Sedlacek, Z; Korn, B; Konecki, D S; Siebenhaar, R; Coy, J F; Kioschis, P; Poustka, A

    1993-11-01

    A transcription map covering a 300 kb region around the G6PD gene in the human Xq28 region was constructed by the direct cDNA selection method and the analysis of the resulting region-specific enriched cDNA sublibrary. Seven new genes and two loci of endogenous retrovirus HERV-K were identified. The distribution of the genes across the region is strongly non-uniform and follows the non-uniform distribution of GpG islands in the area. While one of the novel genes was found to be highly homologous to bovine smg p25A GDP-dissociation inhibitor, the remaining genes did not detect any homology to known genes. The analysis of region-specific cDNA sublibraries represents a simple, rapid and efficient tool for the generation of a regional transcription map.

  20. Glucose-6-phosphate dehydrogenase deficiency: not exclusively in males.

    PubMed

    van den Broek, Leonie; Heylen, Evelien; van den Akker, Machiel

    2016-12-01

    Glucose-6-phosphate (G6PD) deficiency is the most common human enzyme defect, often presenting with neonatal jaundice and/or acute hemolytic anemia, triggered by oxidizing agents. G6PD deficiency is an X-linked, hereditary disease, mainly affecting men, but should also be considered in females with an oxidative hemolysis.

  1. G-6-PD level and surface nanoscopy: a novel approach in ergonomic stress management of female labours in Bengal suburbs performing manual material handling.

    PubMed

    Ghosh, Subrata; Acharyya, Muktish; Bagchi, Anandi

    2009-12-01

    Strenous physical exercise like professional load bearing often produces oxidative stress, increasing post exercise Malondialdehyde (MDA) levels. To quantify the cellular dimension/profile of the said stress, nanoscopic observation of the erythrocyte surface was made by Atomic Forced Microscopy (AFM)/Lateral Forced Microscopy (LFM) and correspondingly the average roughness of the surface was measured. An attempt has been made to correlate the antioxidant vitamin mixture supplementation, endurance capacity, allied physiological parameters and blood glucose-6-phosphate dehydrogenase (G-6-PD) level and roughness-MDA correlation and thereby the deduced regression equation as crucial markers of performance related oxidative stress management in professional female load bearers. Three experimental groups A, B and placebo, each consisting of ten female workers (18-21 years old), were chosen. Group A was given 400 mg of vitamin E supplementation daily, while Group B was given a clinical mixture of vitamin E, vitamin C and beta-carotene daily in capsular form for a period of 28 days. The exercise- induced hike in the status of serum MDA was found to rise less significantly with vitamin supplementation. Further study showed that the supplementation was instrumental in reducing the basal MDA level. Endurance capacity, determined by bicycle ergometric method, was increased more significantly (p < 0.001) in group B than in group A (p < 0.01), and first minute recovery heart rate decreased significantly (p < 0.05) in both groups. G-6-PD level was shown to increase more significantly (p < 0.01) with antioxidant vitamin mixture supplementation than with vitamin E supplementation singly (p < 0.05) in professional female load bearers. The regression equation might be instrumental in early detection of oxidative damage in strenuous exercise in manual material handling.

  2. Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans.

    PubMed

    Yang, H-C; Chen, T-L; Wu, Y-H; Cheng, K-P; Lin, Y-H; Cheng, M-L; Ho, H-Y; Lo, S J; Chiu, D T-Y

    2013-05-02

    Glucose 6-phosphate dehydrogenase (G6PD) deficiency, known as favism, is classically manifested by hemolytic anemia in human. More recently, it has been shown that mild G6PD deficiency moderately affects cardiac function, whereas severe G6PD deficiency leads to embryonic lethality in mice. How G6PD deficiency affects organisms has not been fully elucidated due to the lack of a suitable animal model. In this study, G6PD-deficient Caenorhabditis elegans was established by RNA interference (RNAi) knockdown to delineate the role of G6PD in animal physiology. Upon G6PD RNAi knockdown, G6PD activity was significantly hampered in C. elegans in parallel with increased oxidative stress and DNA oxidative damage. Phenotypically, G6PD-knockdown enhanced germ cell apoptosis (2-fold increase), reduced egg production (65% of mock), and hatching (10% of mock). To determine whether oxidative stress is associated with G6PD knockdown-induced reproduction defects, C. elegans was challenged with a short-term hydrogen peroxide (H2O2). The early phase egg production of both mock and G6PD-knockdown C. elegans were significantly affected by H2O2. However, H2O2-induced germ cell apoptosis was more dramatic in mock than that in G6PD-deficient C. elegans. To investigate the signaling pathways involved in defective oogenesis and embryogenesis caused by G6PD knockdown, mutants of p53 and mitogen-activated protein kinase (MAPK) pathways were examined. Despite the upregulation of CEP-1 (p53), cep-1 mutation did not affect egg production and hatching in G6PD-deficient C. elegans. Neither pmk-1 nor mek-1 mutation significantly affected egg production, whereas sek-1 mutation further decreased egg production in G6PD-deficient C. elegans. Intriguingly, loss of function of sek-1 or mek-1 dramatically rescued defective hatching (8.3- and 9.6-fold increase, respectively) induced by G6PD knockdown. Taken together, these findings show that G6PD knockdown reduces egg production and hatching in C. elegans

  3. Reversible pulmonary trunk banding. IX. G6PD activity of adult goat myocardium submitted to ventricular retraining

    PubMed Central

    Assad, Renato Samy; Miana, Leonardo Augusto; Fonseca-Alaniz, Miriam Helena; Abduch, Maria Cristina Donadio; da Silva, Gustavo José Justo; de Oliveira, Fernanda Santos; Moreira, Luiz Felipe Pinho; Krieger, José Eduardo

    2013-01-01

    Objective Increased glucose 6-phosphate dehydrogenase activity has been demonstrated in heart failure. This study sought to assess myocardial glucose 6-phosphate dehydrogenase activity in retraining of the subpulmonary ventricle of adult goats. Methods Eighteen adult goats were divided into three groups: traditional (fixed banding), sham, and intermittent (adjustable banding, daily 12-hour systolic overload). Systolic overload (70% of systemic pressure) was maintained during a 4-week period. Right ventricle, pulmonary artery and aortic pressures were measured throughout the study. All animals were submitted to echocardiographic and hemodynamic evaluations throughout the protocol. After the study period, the animals were killed for morphological and glucose 6-phosphate dehydrogenase activity assessment. Results A 55.7% and 36.7% increase occurred in the intermittent and traditional right ventricle masses, respectively, when compared with the sham group (P<0.05), despite less exposure of intermittent group to systolic overload. No significant changes were observed in myocardial water content in the 3 groups (P=0.27). A 37.2% increase was found in right ventricle wall thickness of intermittent group, compared to sham and traditional groups (P<0.05). Right ventricle glucose 6-phosphate dehydrogenase activity was elevated in the traditional group, when compared to sham and intermittent groups (P=0.05). Conclusion Both study groups have developed similar right ventricle hypertrophy, regardless less systolic overload exposure of intermittent group. Traditional systolic overload for adult subpulmonary ventricle retraining causes upregulation of myocardial glucose 6-phosphate dehydrogenase activity. It may suggest that the undesirable "pathologic systolic overload" is influenced by activation of penthose pathway and cytosolic Nicotinamide adenine dinucleotide phosphate availability. This altered energy substrate metabolism can elevate levels of free radicals by Nicotinamide

  4. Glucose-6-phosphate dehydrogenase deficiency in northern Mexico and description of a novel mutation.

    PubMed

    García-Magallanes, N; Luque-Ortega, F; Aguilar-Medina, E M; Ramos-Payán, R; Galaviz-Hernández, C; Romero-Quintana, J G; Del Pozo-Yauner, L; Rangel-Villalobos, H; Arámbula-Meraz, E

    2014-08-01

    Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia. G6PD deficiency has scarcely been studied in the northern region of Mexico, which is important because of the genetic heterogeneity described in Mexican population. Therefore, samples from the northern Mexico were biochemically screened for G6PD deficiency, and PCR-RFLPs, and DNA sequencing used to identify mutations in positive samples. The frequency of G6PD deficiency in the population was 0.95% (n = 1993); the mutations in 86% of these samples were G6PD A(-202A/376G), G6PDA(-376G/968C) and G6PD Santamaria(376G/542T). Contrary to previous reports, we demonstrated that G6PD deficiency distribution is relatively homogenous throughout the country (P = 0.48336), and the unique exception with high frequency of G6PD deficiency does not involve a coastal population (Chihuahua: 2.4%). Analysis of eight polymorphic sites showed only 10 haplotypes. In one individual we identified a new G6PD mutation named Mexico DF(193A>G) (rs199474830), which probably results in a damaging functional effect, according to PolyPhen analysis. Proteomic impact of the mutation is also described.

  5. Anemia in patients with coinherited thalassemia and glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Pornprasert, Sakorn; Phanthong, Siratcha

    2013-01-01

    Thalassemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are genetic disorders that cause hemolytic anemia. In areas with high frequencies of both hematological disorders, coinheritance of G-6-PD deficiency with thalassemia can be found. Whether G-6-PD deficiency, coinherited with thalassemia, enhances severe anemia is still unclear. Hematological parameters between thalassemia carriers with G-6-PD deficiency and those without G-6-PD deficiency were compared. The G-6-PD deficiency was diagnosed in 410 blood samples from thalassemia patients using a fluorescent spot test. The levels of hemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV) and Hb A2/Hb E [β26(B8)Glu→Lys; HBB: c.79G>A] were measured using an automated blood counter and high performance liquid chromatography (HPLC), respectively. The G-6-PD deficiency was found in 37 samples (9.02%). Mean levels of Hb, PCV, MCV and Hb A2/E were similar between the two groups. Thus, G-6-PD deficiency did not enhance red blood cell pathology or induce more anemic severity in thalassemia patients.

  6. Glucose-6-phosphate dehydrogenase deficiency and sulfadimidin acetylation phenotypes in Egyptian oases.

    PubMed

    Hussein, L; Yamamah, G; Saleh, A

    1992-04-01

    Screening of 1315 males from two Egyptian oases for glucose-6-phosphate dehydrogenase deficiency (G-6PD) found an incidence of 5.9%. The rate of acetylation of sulfadimidin was also studied, and a bimodal distribution was found with 73% rapid acetylators. There is a correlation between high frequency of G-6PD deficiency and high frequency of slow acetylation rate.

  7. Incidence and mutation analysis of glucose-6-phosphate dehydrogenase deficiency in eastern Indonesian populations.

    PubMed

    Tantular, Indah S; Matsuoka, Hiroyuki; Kasahara, Yuichi; Pusarawati, Suhintam; Kanbe, Toshio; Tuda, Josef S B; Kido, Yasutoshi; Dachlan, Yoes P; Kawamoto, Fumihiko

    2010-12-01

    We conducted a field survey of glucose-6-phosphate dehydrogenese (G6PD) deficiency in the eastern Indonesian islands, and analyzed G6PD variants molecularly. The incidence of G6PD deficiency in 5 ethnic groups (Manggarai, Bajawa, Nage-Keo, Larantuka, and Palue) on the Flores and Palue Islands was lower than that of another native group, Sikka, or a nonnative group, Riung. Molecular analysis of G6PD variants indicated that 19 cases in Sikka had a frequency distribution of G6PD variants similar to those in our previous studies, while 8 cases in Riung had a different frequency distribution of G6PD variants. On the other hand, from field surveys in another 8 ethnic groups (Timorese, Sumbanese, Savunese, Kendari, Buton, Muna, Minahasa, and Sangirese) on the islands of West Timor, Sumba, Sulawesi, Muna and Bangka, a total of 49 deficient cases were detected. Thirty-nine of these 49 cases had G6PD Vanua Lava (383T>C) of Melanesian origin. In our previous studies, many cases of G6PD Vanua Lava were found on other eastern Indonesian islands. Taken together, these findings may indicate that G6PD Vanua Lava is the most common variant in eastern Indonesian populations, except for Sikka.

  8. Glucose-6-Phosphate Dehydrogenase-Deficiency in Transfusion Medicine: The Unknown Risks

    PubMed Central

    Francis, Richard O.; Jhang, Jeffrey S.; Pham, Huy P.; Hod, Eldad A.; Zimring, James C.; Spitalnik, Steven L.

    2013-01-01

    The hallmark of glucose-6-phosphate dehydrogenase (G6PD) deficiency is red blood cell (RBC) destruction in response to oxidative stress. Patients requiring RBC transfusions may simultaneously receive oxidative medications or have concurrent infections, both of which can induce hemolysis in G6PD-deficient RBCs. Although it is not routine practice to screen healthy blood donors for G6PD deficiency, case reports identified transfusion of G6PD-deficient RBCs as causing hemolysis and other adverse events. In addition, some patient populations may be more at risk for complications associated with transfusions of G6PD-deficient RBCs because they receive RBCs from donors who are more likely to have G6PD deficiency. This review discusses G6PD deficiency, its importance in transfusion medicine, changes in the RBC antioxidant system (of which G6PD is essential) during refrigerated storage, and mechanisms of hemolysis. In addition, as yet unanswered questions that could be addressed by translational and clinical studies are identified and discussed. PMID:23815264

  9. Glucose-6-phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks.

    PubMed

    Francis, R O; Jhang, J S; Pham, H P; Hod, E A; Zimring, J C; Spitalnik, S L

    2013-11-01

    The hallmark of glucose-6-phosphate dehydrogenase (G6PD) deficiency is red blood cell (RBC) destruction in response to oxidative stress. Patients requiring RBC transfusions may simultaneously receive oxidative medications or have concurrent infections, both of which can induce haemolysis in G6PD-deficient RBCs. Although it is not routine practice to screen healthy blood donors for G6PD deficiency, case reports identified transfusion of G6PD-deficient RBCs as causing haemolysis and other adverse events. In addition, some patient populations may be more at risk for complications associated with transfusions of G6PD-deficient RBCs because they receive RBCs from donors who are more likely to have G6PD deficiency. This review discusses G6PD deficiency, its importance in transfusion medicine, changes in the RBC antioxidant system (of which G6PD is essential) during refrigerated storage and mechanisms of haemolysis. In addition, as yet unanswered questions that could be addressed by translational and clinical studies are identified and discussed.

  10. Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

    PubMed

    Williams, Olatundun; Gbadero, Daniel; Edowhorhu, Grace; Brearley, Ann; Slusher, Tina; Lund, Troy C

    2013-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females) aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5%) followed by those Igbo descent (10.6%) and those of Igede (10.2%) and Tiv (1.8%) ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females). Yoruba children had a higher prevalence (16.9%) than Igede (10.5%), Igbo (10.1%) and Tiv (5.0%) children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500). The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively). Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351). In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection.

  11. Clinical complications of G6PD deficiency in Latin American and Caribbean populations: systematic review and implications for malaria elimination programmes

    PubMed Central

    2014-01-01

    Background Although G6PDd individuals are generally asymptomatic throughout their life, the clinical burden of this genetic condition includes a range of haematological conditions, including acute haemolytic anaemia (AHA), neonatal jaundice (NNJ) and chronic non-sphaerocytic anaemia (CNSA). In Latin America (LA), the huge knowledge gap regarding G6PDd is related to the scarce understanding of the burden of clinical manifestation underlying G6PDd carriage. The aim of this work was to study the clinical significance of G6PDd in LA and the Caribbean region through a systematic review. Methods A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Only original research was included. All study designs were included, as long as any clinical information was present. Studies were eligible for inclusion if they reported clinical information from populations living in LA or Caribbean countries or about migrants from these countries living in countries outside this continent. Results The Medline search generated 487 papers, and the LILACS search identified 140 papers. After applying the inclusion criteria, 100 original papers with any clinical information on G6PDd in LA were retrieved. Additionally, 16 articles were included after reading the references from these papers. These 116 articles reported data from 18 LA and Caribbean countries. The major clinical manifestations reported from LA countries were those related to AHA, namely drug-induced haemolysis. Most of the published works regarding drug-induced haemolysis in LA referred to haemolytic crises in P. vivax malaria patients during the course of the treatment with primaquine (PQ). Favism, infection-induced haemolysis, NNJ and CNSA appear to play only a minor public health role in this continent. Conclusion Haemolysis in patients using PQ seems to be the major clinical manifestation of G6PDd in LA and contributes to the morbidity of P. vivax infection in this continent, although the low number of reported cases, which could be linked to under-reporting of complications. These results support the need for better strategies to diagnose and manage G6PDd in malaria field conditions. Additionally, Malaria Control Programmes in LA should not overlook this condition in their national guidelines. PMID:24568147

  12. Unsuspected glucose-6-phosphate dehydrogenase deficiency presenting as symptomatic methemoglobinemia with severe hemolysis after fava bean ingestion in a 6-year-old boy.

    PubMed

    Odièvre, Marie-Hélène; Danékova, Névéna; Mesples, Bettina; Chemouny, Myriam; Couque, Nathalie; Parez, Nathalie; Ducrocq, Rolande; Elion, Jacques

    2011-05-01

    We report the occurrence of symptomatic methemoglobinemia in a previously healthy boy, who presented with severe acute hemolysis after fava bean ingestion. The methemoglobinemia revealed a previously unrecognized glucose-6-phosphate dehydrogenase (G6PD) deficiency. We discuss the pathophysiology of severe methemoglobinemia when associated with acute hemolysis, favism, and the common African G6PD A-variant [G6PD, VAL68MET, ASN126ASP]. In conclusion, screening for G6PD deficiency must be considered in symptomatic methemoglobinemia, especially in young boys, when associated with intravascular hemolysis.

  13. Glucose-6-phosphate dehydrogenase and red cell pyruvate kinase deficiency in neonatal jaundice cases in egypt.

    PubMed

    Abdel Fattah, Mohammed; Abdel Ghany, Eman; Adel, Alia; Mosallam, Dalia; Kamal, Shahira

    2010-05-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency can lead to acute hemolytic anemia, chronic nonspherocytic hemolytic anemia, and neonatal jaundice. Neonatal red cell pyruvate kinase (PK) deficiency may cause clinical patterns, ranging from extremely severe hemolytic anemia to moderate jaundice. The authors aimed at studying the prevalence of G6PD and PK deficiency among Egyptian neonates with pathological indirect hyperbilirubinemia in Cairo. This case-series study included 69 newborns with unconjugated hyperbilirubinemia. All were subjected to clinical history, laboratory investigations, e.g., complete blood counts, reticulocytic counts, direct and indirect serum bilirubin levels, Coombs tests, qualitative assay of G6PD activity by methemoglobin reduction test, and measurement of erythrocytic PK levels. The study detected 10 neonates with G6PD deficiency, which means that the prevalence of G6PD deficiency among Egyptian neonates with hyperbilirubinemia is 14.4% (21.2% of males). G6PD deficiency was significantly higher in males than females (P = .01). The authors detected 2 cases with PK deficiency, making the prevalence of its deficiency 2.8%. These data demonstrate that G6PD deficiency is an important cause for neonatal jaundice in Egyptians. Neonatal screening for its deficiency is recommended. PK deficiency is not a common cause of neonatal jaundice. However, this needs further investigation on a larger scale.

  14. Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates.

    PubMed

    M Abo El Fotoh, Wafaa Moustafa; Rizk, Mohammed Soliman

    2016-12-01

    The enzyme, Glucose-6-phosphate dehydrogenase (G6PD), deficiency leads to impaired production of reduced glutathione and predisposes the red cells to be damaged by oxidative metabolites, causing hemolysis. Deficient neonates may manifest clinically as hyperbilirubinemia or even kernicterus. This study was carried out to detect erythrocyte G6PD deficiency in neonatal hyperbilirubinemia. To determine the frequency and effect of G6PD deficiency, this study was conducted on 202 neonates with indirect hyperbilirubinemia. All term and preterm babies up to 13 day of age admitted with clinically evident jaundice were taken for the study. G6PD activity is measured by the UV-Kinetic Method using cellular enzyme determination reagents by spectrophotometry according to manufacturer's instructions. A total of 202 babies were enrolled in this study. Male babies outnumbered the female (71.3% versus 28.7%). Mean age of the study newborns was 3.75 ± 2.5 days. Eighteen neonates (8.9%) had G6PD deficiency, all are males. One case had combined G6PD deficiency and RH incompatibility. Mean serum total bilirubin was 17.2 ± 4.4 in G6PD deficient cases. There was significant positive correlation between the time of appearance of jaundice in days and G6PD levels in G6PD deficient cases. Neonatal hyperbilirubinemia is associated with various clinical comorbidities. G6PD deficiency is found to one important cause of neonatal jaundice developing on day 2 onwards.

  15. Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia.

    PubMed Central

    Vulliamy, T J; D'Urso, M; Battistuzzi, G; Estrada, M; Foulkes, N S; Martini, G; Calabro, V; Poggi, V; Giordano, R; Town, M

    1988-01-01

    Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is a common genetic abnormality affecting an estimated 400 million people worldwide. Clinical and biochemical analyses have identified many variants exhibiting a range of phenotypes, which have been well characterized from the hematological point of view. However, until now, their precise molecular basis has remained unknown. We have cloned and sequenced seven mutant G6PD alleles. In the nondeficient polymorphic African variant G6PD A we have found a single point mutation. The other six mutants investigated were all associated with enzyme deficiency. In one of the commonest, G6PD Mediterranean, which is associated with favism among other clinical manifestations, a single amino acid replacement was found (serine----phenylalanine): it must be responsible for the decreased stability and the reduced catalytic efficiency of this enzyme. Single point mutations were also found in G6PD Metaponto (Southern Italy) and in G6PD Ilesha (Nigeria), which are asymptomatic, and in G6PD Chatham, which was observed in an Indian boy with neonatal jaundice. In G6PD "Matera," which is now known to be the same as G6PD A-, two separate point mutations were found, one of which is the same as in G6PD A. In G6PD Santiago, a de novo mutation (glycine----arginine) is associated with severe chronic hemolytic anemia. The mutations observed show a striking predominance of C----T transitions, with CG doublets involved in four of seven cases. Thus, diverse point mutations may account largely for the phenotypic heterogeneity of G6PD deficiency. Images PMID:3393536

  16. Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: biochemical versus genetic technologies.

    PubMed

    Kaplan, Michael; Hammerman, Cathy

    2011-06-01

    Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, a commonly occurring genetic condition, is associated in neonates with severe hemolytic episodes, extreme hyperbilirubinemia, and bilirubin encephalopathy. Neonatal screening programs for the condition should increase parental and caretaker awareness, thereby facilitating early access to treatment with resultant diminished mortality and morbidity. However, screening for G-6-PD deficiency is not widely performed. Although G-6-PD-deficient males may be accurately identified, females are more difficult to categorize because many in this group may be heterozygotes with phenotype overlap between normal homozygotes, heterozygotes, and deficient homozygotes. Screening methodologies include biochemical qualitative assays, quantitative enzymatic activity measurements and DNA-based polymerase chain reaction molecular screening. The appropriateness of any of these technologies for any particular population group or geographic area must be assessed before setting up a screening program. The pros and cons of each method, including ease of testing, cost, need for sophisticated laboratory equipment and degree of personnel training, as well as the ability to identify females, are discussed.

  17. Periodontal considerations in a patient with glucose-6-phosphate dehydrogenase deficiency with associated pancytopenia: A rare case report.

    PubMed

    Gupta, Harinder; Arora, Ruchika; Kamboj, Monika

    2014-03-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme defect in humans. G6PD deficiency is widely distributed in tropical and subtropical parts of the world and a conservative estimate is that at least 500 million people have a G6PD deficient gene. In several of these areas, the frequency of a G6PD deficiency gene may be as high as 20% or more. The vast majority of people with G6PD deficiency remain clinically asymptomatic throughout their lifetime. However, all of them have an increased risk of developing neonatal jaundice and a risk of developing acute hemolytic anemia when challenged by a number of oxidative agents. The most important treatment measure is prevention: Avoidance of the drugs and foods that cause hemolysis.

  18. Cryopreservation of glucose-6-phosphate dehydrogenase activity inside red blood cells: developing a specimen repository in support of development and evaluation of glucose-6-phosphate dehydrogenase deficiency tests.

    PubMed

    Kahn, Maria; LaRue, Nicole; Bansil, Pooja; Kalnoky, Michael; McGray, Sarah; Domingo, Gonzalo J

    2013-08-20

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzyme deficiency. It is characterized by abnormally low levels of G6PD activity. Individuals with G6PD deficiency are at risk of undergoing acute haemolysis when exposed to 8‒aminoquinoline-based drugs, such as primaquine. For this reason it is imperative to identify individuals with G6PD deficiency prior to administering these anti-malarial drugs. There is a need for the development and evaluation of point-of-care G6PD deficiency screening tests suitable for areas of the developing world where malarial treatments are frequently administered. The development and evaluation of new G6PD tests will be greatly assisted with the availability of specimen repositories. Cryopreservation of erythrocytes was evaluated as a means to preserve G6PD activity. Blood specimens from 31 patients including ten specimens with normal G6PD activity, three with intermediate activity, and 18 with deficient activity were cryopreserved for up to six months. Good correlation in G6PD activity between fresh and cryopreserved specimens (R2 = 0.95). The cryopreserved specimens show an overall small drop in mean G6PD activity of 0.23 U/g Hb (P=0.23). Cytochemical staining showed that intracellular G6PD activity distribution within the red blood cell populations is preserved during cryopreservation. Furthermore, the mosaic composition of red blood cells in heterozygous women is also preserved for six months or more. The fluorescent spot and the BinaxNOW qualitative tests for G6PD deficiency also showed high concordance in G6PD status determination between cryopreserved specimens and fresh specimens. A methodology for establishing a specimen panel for evaluation of G6PD tests is described. The approach is similar to that used in several malaria research facilities for the cryopreservation of parasites in clinical specimens and axenic cultures. Specimens stored in this manner will aid both the development and evaluation of

  19. High prevalence of anaemia among African migrants in Germany persists after exclusion of iron deficiency and erythrocyte polymorphisms.

    PubMed

    Müller, Sophie A; Amoah, Stephen K B; Meese, Stefanie; Spranger, Joachim; Mockenhaupt, Frank P

    2015-09-01

    Haematological parameters differ between individuals of African and European ancestry. However, respective data of first-generation African migrants are virtually absent. We assessed these in Ghanaian migrants living in Berlin, compared them with reference data from Germany and Ghana, and estimated the role of iron deficiency (ID) and erythrocyte polymorphisms in anaemia. A total of 576 Ghanaians (median age, 45 years) were analysed. Blood counts were performed, haemoglobinopathies and glucose-6-phosphate dehydrogenase (G6PD) deficiency were genotyped, and concentrations of ferritin and C-reactive protein were measured to define ID. Most individuals had resided in Germany for more than a decade (median, 18 years). By WHO definition, anaemia was present in 30.9% of females and 9.4% of males. Median haemoglobin (Hb) levels were lower than among Germans (women, -0.8 g/dl, men, -0.7 g/dl). However, applying reference values from Ghana, only 1.9% of the migrants were considered anaemic. Alpha-thalassaemia, Hb variants and G6PD deficiency were observed in 33.9%, 28.3% and 23.6%, respectively. ID was highly prevalent in women (32.0%; men, 3.9%). The population fraction of anaemia cases attributable to ID was 29.0% (alpha-thalassaemia, 13.6%; G6PD deficiency, 13.5%). Nevertheless, excluding ID, alpha-thalassaemia, G6PD deficiency and sickle cell disease, anaemia prevalence remained high (women, 18.4%; men, 6.5%), and was also high when applying uncensored thresholds proposed for African Americans (females, 19.3%; males, 7.8%). Iron deficiency and erythrocyte polymorphisms are common among first-generation Ghanaian migrants but explain only part of the increased prevalence of anaemia. Common Hb thresholds for the definition of anaemia may not be appropriate for this group. © 2015 John Wiley & Sons Ltd.

  20. Hematological parameters and red blood cell morphological abnormality of Glucose-6-Phosphate dehydrogenase deficiency co-inherited with thalassemia.

    PubMed

    Pengon, Jutharat; Svasti, Saovaros; Kamchonwongpaisan, Sumalee; Vattanaviboon, Phantip

    2017-06-15

    Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and thalassemia are genetically independent hemolytic disorders. Co-inheritance of both disorders may affect red blood cell pathology to a greater extent than normally seen in either disorder alone. This study determines the prevalence and evaluates hematological changes of G-6-PD deficiency and thalassemia co-inheritance. G-6-PD deficiency was screened from 200 male thalassemia blood samples using a fluorescent spot test. Hematological parameters and red blood cell morphology were evaluated among G-6-PD deficiency/thalassemia co-inheritance, G-6-PD deficiency alone, thalassemia alone, and normal individuals. G-6-PD deficiency was detected together with hemoglobin (Hb) E heterozygote, Hb E homozygote, β-thalassemia trait, and β-thalassemia/Hb E, α-thalassemia-2 trait, and Hb H disease. Hb level, hematocrit, mean cell volume, and mean cell Hb of G-6-PD deficiency co-inherited with asymptomatic thalassemia carriers show significantly lower mean values compared to carriers with only the same thalassemia genotypes. Higher mean red blood cell distribution width was observed in G-6-PD deficiency co-inherited with Hb E heterozygote, as with numbers of hemighost cells in G-6-PD deficiency/thalassemia co-inheritance compared to those with either disorder. Apart from Hb level, hematological parameters of co-inheritance disorders were not different from individuals with a single thalassemia disease. G-6-PD deficiency co-inherited with thalassemia in males was present in 10% of the participants, resulting in worsening of red blood cell pathology compared with inheritance of thalassemia alone. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  1. Decreased Glutathione S-transferase Level and Neonatal Hyperbilirubinemia Associated with Glucose-6-phosphate Dehydrogenase Deficiency: A Perspective Review.

    PubMed

    Al-Abdi, Sameer Yaseen

    2017-02-01

    Classically, genetically decreased bilirubin conjugation and/or hemolysis account for the mechanisms contributing to neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, these mechanisms are not involved in most cases of this hyperbilirubinemia. Additional plausible mechanisms for G6PD deficiency-associated hyperbilirubinemia need to be considered. Glutathione S-transferases (GST) activity depends on a steady quantity of reduced form of glutathione (GSH). If GSH is oxidized, it is reduced back by glutathione reductase, which requires the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH). The main source of NADPH is the pentose phosphate pathway, in which G6PD is the first enzyme. Rat kidney GSH, rat liver GST, and human red blood cell GST levels have been found to positively correlate with G6PD levels in their respective tissues. As G6PD is expressed in hepatocytes, it is expected that GST levels would be significantly decreased in hepatocytes of G6PD-deficient neonates. As hepatic GST binds bilirubin and prevents their reflux into circulation, hypothesis that decreased GST levels in hepatocytes is an additional mechanism contributing to G6PD deficiency-associated hyperbilirubinemia seems plausible. Evidence for and against this hypothesis are discussed in this article hoping to stimulate further research on the role of GST in G6PD deficiency-associated hyperbilirubinemia.

  2. Glucose-6-phosphate dehydrogenase deficiency among children attending the Emergency Paediatric Unit of Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria.

    PubMed

    Isaac, Iz; Mainasara, As; Erhabor, Osaro; Omojuyigbe, St; Dallatu, Mk; Bilbis, Ls; Adias, Tc

    2013-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human enzyme deficiencies in the world. It is particularly common in populations living in malaria-endemic areas, affecting more than 400 million people worldwide. This present study was conducted with the aim of determining the prevalence of G6PD deficiency among children visiting the Emergency Paediatric Unit of Usmanu Danfodiyo University Teaching Hospital for pediatric-related care. The study included 118 children, made up of 77 (65.3%) males and 41 (34.7%) females aged ≤5 years with mean age of 3.26 ± 1.90 years. Randox G6PD quantitative in vitro test screening was used for the diagnosis of G6PD deficiency. Of the 118 children tested, 17 (14.4%) were G6PD-deficient. Prevalence of G6PD deficiency was concentrated predominantly among male children (22.1%). Male sex was significantly correlated with G6PD deficiency among the children studied (r = 7.85, P = 0.01). The highest prevalence occurred among children in the 2- to 5-year age-group. Of the 17 G6PD-deficient children, twelve (70.2%) were moderately deficient, while five (29.4%) were severely deficient. Blood film from G6PD-deficient children indicated the following morphological changes; Heinz bodies, schistocytes, target cells, nucleated red cells, spherocytes, and polychromasia. This present study has shown a high prevalence of G6PD deficiency among children residing in Sokoto in the northwestern geopolitical zone of Nigeria. The study indicated a male sex bias in the prevalence of G6PD deficiency among the children studied. There is a need for the routine screening of children for G6PD deficiency in our environment, to allow for evidence-based management of these children and to ensure the avoidance of food, drugs, and infective agents that can potentially predispose these children to oxidative stress as well as diseases that deplete micronutrients that protect against oxidative stress. There is need to build capacity in our

  3. Rapid epidemiologic assessment of glucose-6-phosphate dehydrogenase deficiency in malaria-endemic areas in Southeast Asia using a novel diagnostic kit.

    PubMed

    Jalloh, A; Tantular, I S; Pusarawati, S; Kawilarang, A P; Kerong, H; Lin, K; Ferreira, M U; Matsuoka, H; Arai, M; Kita, K; Kawamoto, F

    2004-05-01

    We recently reported a new rapid screening method for glucose-6-phosphate dehydrogenase (G6PD) deficiency. This method incorporates a new formazan substrate (WST-8) and is capable of detecting heterozygous females both qualitatively and quantitatively. Here, we report its evaluation during field surveys at three malaria centres and in malaria-endemic villages of Myanmar and Indonesia, either alone or in combination with a rapid on-site diagnosis of malaria. A total of 57 severe (45 males and 12 females) and 34 mild (five males and 29 females) cases of G6PD deficiency were detected among 855 subjects in Myanmar whilst 30 severe (25 males and five females) and 23 mild (six males and 17 females) cases were found among 1286 subjects in Indonesia. In all cases, severe deficiency was confirmed with another formazan method but due to limitations in its detection threshold, mild cases were misdiagnosed as G6PD-normal by this latter method. Our results indicate that the novel method can qualitatively detect both severely deficient subjects as well as heterozygous females in the field. The antimalarial drug, primaquine, was safely prescribed to Plasmodium vivax-infected patients in Myanmar. Our new, rapid screening method may be essential for the diagnosis of G6PD deficiency particularly in rural areas without electricity, and can be recommended for use in malaria control programmes.

  4. Molecular Characterization of Glucose-6-phosphate Dehydrogenase Deficiency in Families from the Republic of Macedonia and Genotype-phenotype Correlation

    PubMed Central

    Cherepnalkovski, Anet Papazovska; Zemunik, Tatijana; Glamocanin, Sofijanka; Piperkova, Katica; Gunjaca, Ivana; Kocheva, Svetlana; Jovanova, Biljana Coneska; Krzelj, Vjekoslav

    2015-01-01

    Introduction: Glucose-6-phospahte dehydrogenase deficiency (G6PD) is one of the most common inherited disorders affecting around 400 million people worldwide. Molecular analysis of the G6PD gene identified more than 140 distinct mutations, the majority being single base missense mutations. G6PD Mediterranean is the most common variant found in populations of the Mediterranean area. Aim: The aim of our study was to perform molecular characterization of G6PD deficiency in families from the Republic of Macedonia and correlate the findings to disease phenotype. Patients and methods: Six patients and seven other family members were selected for genetic characterization, the selection procedure involved clinical evaluation and G6PD quantitative testing. All patients were first screened for the Mediterranean mutation, and subsequently for the Seattle mutation. Mutations were detected using PCR amplification and appropriate restriction endonuclease cleavage. Results: Four hemizygote and 3 heterozygous carriers for G6PD Mediterranean were detected. All G6PD deficient patients from this group showed clinical picture of hemolysis, and in 66.6% neonatal jaundice was confirmed based on history data. To our knowledge, this is the first study concerned with molecular aspects of the G6PD deficiency in R. Macedonia. Conclusion: This study represents a step towards a more comprehensive genetic evaluation in our population and better understanding of the health issues involved. PMID:26622077

  5. Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease

    PubMed Central

    Hecker, Peter A.; Leopold, Jane A.; Gupte, Sachin A.; Recchia, Fabio A.

    2013-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-determining step in the pentose phosphate pathway and produces NADPH to fuel glutathione recycling. G6PD deficiency is the most common enzyme deficiency in humans and affects over 400 million people worldwide; however, its impact on cardiovascular disease is poorly understood. The glutathione pathway is paramount to antioxidant defense, and G6PD-deficient cells do not cope well with oxidative damage. Limited clinical evidence indicates that G6PD deficiency may be associated with hypertension. However, there are also data to support a protective role of G6PD deficiency in decreasing the risk of heart disease and cardiovascular-associated deaths, perhaps through a decrease in cholesterol synthesis. Studies in G6PD-deficient (G6PDX) mice are mixed and provide evidence for both protective and deleterious effects. G6PD deficiency may provide a protective effect through decreasing cholesterol synthesis, superoxide production, and reductive stress. However, recent studies indicate that G6PDX mice are moderately more susceptible to ventricular dilation in response to myocardial infarction or pressure overload-induced heart failure. Furthermore, G6PDX hearts do not recover as well as nondeficient mice when faced with ischemia-reperfusion injury, and G6PDX mice are susceptible to the development of age-associated cardiac hypertrophy. Overall, the limited available data indicate a complex interplay in which adverse effects of G6PD deficiency may outweigh potential protective effects in the face of cardiac stress. Definitive clinical studies in large populations are needed to determine the effects of G6PD deficiency on the development of cardiovascular disease and subsequent outcomes. PMID:23241320

  6. Glucose-6-Phosphate Dehydrogenase Deficiency Improves Insulin Resistance With Reduced Adipose Tissue Inflammation in Obesity.

    PubMed

    Ham, Mira; Choe, Sung Sik; Shin, Kyung Cheul; Choi, Goun; Kim, Ji-Won; Noh, Jung-Ran; Kim, Yong-Hoon; Ryu, Je-Won; Yoon, Kun-Ho; Lee, Chul-Ho; Kim, Jae Bum

    2016-09-01

    Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses. © 2016 by the American Diabetes Association.

  7. Glucose-6-phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose.

    PubMed

    Phillpotts, Simon; Tash, Elliot; Sen, Sambit

    2014-11-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol-induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy.

  8. Hemolytic anemia caused by glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Olivares, N; Medina, C; Sánchez-Corona, J; Rivas, F; Rivera, H; Hernández, A; Delgado, J L; Ibarra, B; Cantú, J M; Vaca, G; Martínez, C

    1979-01-01

    Results are reported concerning quantitation of glucose -6- phosphate dehydrogenase (G6PD) enzyme activity where in one of the members of a family a clinical diagnosis of acute hemolytic anemia due to G6PD deficiency had been established. In the propositus, G6PD levels were found to be less than 10 per cent thus confirming diagnosis; the same enzymatic deficiency was identified in one of the siblings without a history of hematologic pathology and in a maternal cousin with a history of neonatal jaundice as well as two obliged carriers. Electrophoretical enzyme phenotype was similar to A variant in three affected males. Advantages of prevention and medical care possible with early diagnosis of G6PD deficiency are discussed.

  9. Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border.

    PubMed

    Li, Qing; Yang, Fang; Liu, Rong; Luo, Lan; Yang, Yuling; Zhang, Lu; Liu, Huaie; Zhang, Wen; Fan, Zhixiang; Yang, Zhaoqing; Cui, Liwang; He, Yongshu

    2015-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary disease that predisposes red blood cells to oxidative damage. G6PD deficiency is particularly prevalent in historically malaria-endemic areas. Use of primaquine for malaria treatment may result in severe hemolysis in G6PD deficient patients. In this study, we systematically evaluated the prevalence of G6PD deficiency in the Kachin (Jingpo) ethnic group along the China-Myanmar border and determined the underlying G6PD genotypes. We surveyed G6PD deficiency in 1770 adult individuals (671 males and 1099 females) of the Kachin ethnicity using a G6PD fluorescent spot test. The overall prevalence of G6PD deficiency in the study population was 29.6% (523/1770), among which 27.9% and 30.6% were males and females, respectively. From these G6PD deficient samples, 198 unrelated individuals (147 females and 51 males) were selected for genotyping at 11 known G6PD single nucleotide polymorphisms (SNPs) in Southeast Asia (ten in exons and one in intron 11) using a multiplex SNaPshot assay. Mutations with known association to a deficient phenotype were detected in 43.9% (87/198) of cases, intronic and synonymous mutations were detected alone in 34.8% (69/198) cases and no mutation were found in 21.2% (42/198) cases. Five non-synonymous mutations, Mahidol 487G>A, Kaiping 1388G>A, Canton 1376G>T, Chinese 4 392G>T, and Viangchan 871G>A were detected. Of the 87 cases with known deficient mutations, the Mahidol variant was the most common (89.7%; 78/87), followed by the Kaiping (8.0%; 7/87) and the Viangchan (2.2%; 2/87) variants. The Canton and Chinese 4 variants were found in 1.1% of these 87 cases. Among them, two females carried the Mahidol/Viangchan and Mahidol/Kaiping double mutations, respectively. Interestingly, the silent SNPs 1311C>T and IVS11nt93T>C both occurred in the same 95 subjects with frequencies at 56.4% and 23.5% in tested females and males, respectively (P<0.05). It is noteworthy that 24

  10. Glucose-6-phosphate dehydrogenase deficiency in Chinese

    PubMed Central

    Lai, H. C.; Lai, Michael P. Y.; Leung, Kevin S. N.

    1968-01-01

    In a Chinese population 1,000 full-term male neonates and a further 117 jaundiced neonates of both sexes were studied in an investigation of the frequency of deficiency of erythrocyte glucose-6-phosphate dehydrogenase (G6PD). This enzyme was found to be deficient in 3·6% of male neonates. Correlation of the results with the birthplace of the 602 mothers who were known to come from Kwangtung province showed no significant differences in the frequency of the deficiency between certain parts of the province. The deficiency of G6PD in hemizygous males is profound but it is not associated with erythrocyte acid monophosphoesterase deficiency in Chinese in Hong Kong. The G6PD deficiency accounts for 15·4% of all the 117 cases of neonatal jaundice. The relative importance of G6PD deficiency as a cause of neonatal jaundice does not differ materially in male and female mutants. Neonatal jaundice can occur in all genotypes of G6PD mutation in Chinese. PMID:5697334

  11. The Preterm Infant: A High-Risk Situation for Neonatal Hyperbilirubinemia Due to Glucose-6-Phosphate Dehydrogenase Deficiency.

    PubMed

    Kaplan, Michael; Hammerman, Cathy; Bhutani, Vinod K

    2016-06-01

    Prematurity and glucose-6-phosphate dehydrogenase (G6PD) deficiency are risk factors for neonatal hyperbilirubinemia. The 2 conditions may interact additively or synergistically, contributing to extreme hyperbilirubinemia, with the potential for bilirubin neurotoxicity. This hyperbilirubinemia is the result of sudden, unpredictable, and acute episodes of hemolysis in combination with immaturity of bilirubin elimination, primarily of conjugation. Avoidance of contact with known triggers of hemolysis in G6PD-deficient individuals will prevent some, but not all, episodes of hemolysis. All preterm infants with G6PD deficiency should be vigilantly observed for the development of jaundice both in hospital and after discharge home.

  12. High frequency of diabetes and impaired fasting glucose in patients with glucose-6-phosphate dehydrogenase deficiency in the Western brazilian Amazon.

    PubMed

    Santana, Marli S; Monteiro, Wuelton M; Costa, Mônica R F; Sampaio, Vanderson S; Brito, Marcelo A M; Lacerda, Marcus V G; Alecrim, Maria G C

    2014-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, and it has a significant prevalence in the male population (X chromosome linked). The purpose of this study was to estimate the frequency of impaired fasting glucose and diabetes among G6PD-deficient persons in Manaus, Brazil, an area in the Western Brazilian Amazon to which malaria is endemic. Glucose-6-phosphate dehydrogenase-deficient males had more impaired fasting glucose and diabetes. This feature could be used as a screening tool for G6PD-deficient persons who are unable to use primaquine for the radical cure of Plasmodium vivax malaria.

  13. Is glucose-6-phosphate dehydrogenase deficiency more prevalent in Carrion's disease endemic areas in Latin America?

    PubMed

    Mazulis, Fernando; Weilg, Claudia; Alva-Urcia, Carlos; Pons, Maria J; Del Valle Mendoza, Juana

    2015-12-01

    Glucose-6-phosphate dehydrogenase (G6PD) is a cytoplasmic enzyme with an important function in cell oxidative damage prevention. Erythrocytes have a predisposition towards oxidized environments due to their lack of mitochondria, giving G6PD a major role in its stability. G6PD deficiency (G6PDd) is the most common enzyme deficiency in humans; it affects approximately 400 million individuals worldwide. The overall G6PDd allele frequency across malaria endemic countries is estimated to be 8%, corresponding to approximately 220 million males and 133 million females. However, there are no reports on the prevalence of G6PDd in Andean communities where bartonellosis is prevalent.

  14. Screening for Glucose-6-Phosphate Dehydrogenase Deficiency Using Three Detection Methods: A Cross-Sectional Survey in Southwestern Uganda.

    PubMed

    Roh, Michelle E; Oyet, Caesar; Orikiriza, Patrick; Wade, Martina; Mwanga-Amumpaire, Juliet; Boum, Yap; Kiwanuka, Gertrude N; Parikh, Sunil

    2016-11-02

    Despite the potential benefit of primaquine in reducing Plasmodium falciparum transmission and radical cure of Plasmodium vivax and Plasmodium ovale infections, concerns over risk of hemolytic toxicity in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd) have hampered its deployment. A cross-sectional survey was conducted in 2014 to assess the G6PDd prevalence among 631 children between 6 and 59 months of age in southwestern Uganda, an area where primaquine may be a promising control measure. G6PDd prevalence was determined using three detection methods: a quantitative G6PD enzyme activity assay (Trinity Biotech(®) G-6-PDH kit), a qualitative point-of-care test (CareStart(™) G6PD rapid diagnostic test [RDT]), and molecular detection of the G6PD A- G202A allele. Qualitative tests were compared with the gold standard quantitative assay. G6PDd prevalence was higher by RDT (8.6%) than by quantitative assay (6.8%), using a < 60% activity threshold. The RDT performed optimally at a < 60% threshold and demonstrated high sensitivity (≥ 90%) and negative predictive values (100%) across three activity thresholds (below 60%, 30%, and 40%). G202A allele frequency was 6.4%, 7.9%, and 6.8% among females, males, and overall, respectively. Notably, over half of the G202A homo-/hemizygous children expressed ≥ 60% enzyme activity. Overall, the CareStart(™) G6PD RDT appears to be a viable screening test to accurately identify individuals with enzyme activities below 60%. The low prevalence of G6PDd across all three diagnostic modalities and absence of severe deficiency in our study suggests that there is little barrier to the use of single-dose primaquine in this region.

  15. [Glucose 6-phosphate dehydrogenase deficiency: a protection against malaria and a risk for hemolytic accidents].

    PubMed

    Wajcman, Henri; Galactéros, Frédéric

    2004-08-01

    Glucose 6-phosphate dehydrogenase (G6PD) catalyses the first step of the pentose phosphate pathway, which in the RBC leads to the formation of NADPH, essential to prevent the cell from an oxidative stress. Worldwide, more than 400 million people (90% being males) are affected by G6PD deficiency, in regions that are, or have been, endemic for malaria and in populations originating from these regions. RBCs with low G6PD activity offer a hostile environment to parasite growth and thus an advantage to G6PD deficiency carriers. The counterpart of this protective effect is an increased susceptibility to oxidants such as some foods (fava beans), drugs (anti-malarial or sulphonamides), or various chemicals. In the case of G6PD deficiency, the hypothesis of a convergent evolution between parasite, protecting mutation, and cultural traditions (food, skin painting...) has been proposed. Near to 150 different G6PD variants have been described, which are classified into four types, according to their clinical effects. Several variants, such as the G6PD A- or the Mediterranean variant, reach the polymorphism level in endemic regions. The recent determination of the three-dimensional structure of this enzyme allows one to explain now the mechanisms of the disorders in terms of structure-function relationship.

  16. Inhibitory effect of a fava bean component on the in vitro development of Plasmodium falciparum in normal and glucose-6-phosphate dehydrogenase deficient erythrocytes.

    PubMed

    Golenser, J; Miller, J; Spira, D T; Navok, T; Chevion, M

    1983-03-01

    We examined the hypothesis that G-6-PD deficiency associated with fava bean ingestion confers resistance to malaria by studying the in vitro interactions between malaria parasites (Plasmodium falciparum), human erythrocytes with varying degrees of G-6-PD deficiency, and isouramil (IU), a fava bean extract that is known to cause oxidant stress and hemolysis of G-6-PD-deficient erythrocytes. Untreated G-6-PD-deficient and normal erythrocytes supported the in vitro growth of P. falciparum equally well. However, after pretreatment with IU, G-6-PD-deficient erythrocytes did not support parasite growth in vitro, whereas growth remained high in normal erythrocytes. Parasite growth was proportional to the G-6-PD activity of the IU-treated erythrocytes. In contrast, when parasitized erythrocytes were exposed to IU, parasites even in normal erythrocytes were destroyed. Ring forms were much less sensitive than late trophozoites and schizonts. The results suggest that there are two modes by which IU affects the development of P. falciparum and demonstrate in vitro that G-6-PD deficiency confers resistance against malaria under conditions of fava-bean-associated oxidant stress.

  17. An audit of the precipitating factors for haemolytic crisis among glucose-6-phosphate dehydrogenase-deficient paediatric patients.

    PubMed

    Al-Azzam, Sayer I; Al-Ajlony, Mohammad J; Al-Khateeb, Taqwa; Alzoubi, Karem H; Mhaidat, Nizar; Ayoub, Abeer

    2009-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common genetic enzyme deficiencies leading to haemolytic anaemia. This study aimed to investigate the precipitating factors for haemolytic crisis in G6PD-deficient paediatric patients in Jordan. A retrospective study of data from the records of 258 paediatric patients admitted to a major paediatric hospital in North Jordan from January 2001 until April 2007. Patients included were G6PD-deficient children who were admitted to the hospital secondary to an episode of haemolytic anaemia. Of 258 paediatric patients, 244 (94.2%) had developed a haemolytic episode secondary to ingestion of fava beans. The remaining 14 children (5.8%) developed a haemolytic episode triggered by other factors, such as drugs and upper respiratory infections. Fava bean ingestion is the major precipitating factor for haemolytic anaemia episodes among G6PD-deficient children in Jordan.

  18. Aortic valve replacement for a patient with glucose-6-phosphate dehydrogenase deficiency and autoimmune hemolytic anemia.

    PubMed

    Tas, Serpil; Donmez, Arzu Antal; Kirali, Kaan; Alp, Mete H; Yakut, Cevat

    2005-01-01

    Autoimmune hemolytic anemia and deficiency of glucose-6-phosphate deyhdrogenase (G6PD) result in severe hemolysis with different mechanisms. In patients with both pathologies, the effects of cardiopulmonary bypass on red blood cells and thrombocytes demand special care before and after open heart surgery. We evaluated the preoperative management and postoperative care of a patient with severe aortic insufficiency associated with G6PD deficiency and autoimmune hemolytic anemia who underwent aortic valve replacement.

  19. Contribution of haemolysis to jaundice in Sephardic Jewish glucose-6-phosphate dehydrogenase deficient neonates.

    PubMed

    Kaplan, M; Vreman, H J; Hammerman, C; Leiter, C; Abramov, A; Stevenson, D K

    1996-06-01

    We determined the contribution of haemolysis to the development of hyperbilirubinaemia in glucose-6-phosphate dehydrogenase (G-6-PD) deficient neonates and G-6-PD normal controls. Blood carboxyhaemoglobin (COHb), sampled on the third day of life, was measured by gas chromatography, corrected for inhaled carbon monoxide (COHbC), and expressed as a percentage of total haemoglobin concentration (Hb). Serum bilirubin was tested as clinically necessary. 37 non-jaundiced (peak serum total bilirubin (PSTB) < or = 255 mumol/l) and 20 jaundiced (PSTB > or = 257 mumol/l) G-6-PD-deficient neonates were compared to 31 non-jaundiced and 24 jaundiced controls with comparable PSTB values, respectively. COHbC values for the entire G-6-PD deficient group were higher than in the controls (0.75 +/- 0.17% v 0.62 +/- 0.19%, P < 0.001). COHbC and PSTB values did not correlate in the G-6-PD-deficient group (r = 0.15, P > 0.05) but did in the controls (r = 0.58, P < 0.001). COHbC values were increased to a similar extent in the G-6-PD-deficient, non-jaundiced (0.72 +/- 0.16%), the G-6-PD-deficient, jaundiced (0.80 +/- 0.19%) and the control, jaundiced (0.75 +/- 0.18%) subgroups, compared to the control, non-jaundiced subgroup (0.53 +/- 0.13%) (P < 0.05). Although present in G-6-PD deficient neonates, increased haemolysis was not directly related to the PSTB.

  20. Somatic-cell selection is a major determinant of the blood-cell phenotype in heterozygotes for glucose-6-phosphate dehydrogenase mutations causing severe enzyme deficiency.

    PubMed Central

    Filosa, S.; Giacometti, N.; Wangwei, C.; De Mattia, D.; Pagnini, D.; Alfinito, F.; Schettini, F.; Luzzatto, L.; Martini, G.

    1996-01-01

    X-chromosome inactivation in mammals is regarded as an essentially random process, but the resulting somatic-cell mosaicism creates the opportunity for cell selection. In most people with red-blood-cell glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme-deficient phenotype is only moderately expressed in nucleated cells. However, in a small subset of hemizygous males who suffer from chronic nonspherocytic hemolytic anemia, the underlying mutations (designated class I) cause more-severe G6PD deficiency, and this might provide an opportunity for selection in heterozygous females during development. In order to test this possibility we have analyzed four heterozygotes for class I G6PD mutations: two with G6PD Portici (1178G-->A) and two with G6PD Bari (1187C-->T). We found that in fractionated blood cell types (including erythroid, myeloid, and lymphoid cell lineages) there was a significant excess of G6PD-normal cells. The significant concordance that we have observed in the degree of imbalance in the different blood-cell lineages indicates that a selective mechanism is likely to operate at the level of pluripotent blood stem cells. Thus, it appears that severe G6PD deficiency affects adversely the proliferation or the survival of nucleated blood cells and that this phenotypic characteristic is critical during hematopoiesis. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8808605

  1. Somatic-cell selection is a major determinant of the blood-cell phenotype in heterozygotes for glucose-6-phosphate dehydrogenase mutations causing severe enzyme deficiency

    SciTech Connect

    Filosa, S.; Giacometti, N.; Wangwei, C.; Martini, G.

    1996-10-01

    X-chromosome inactivation in mammals is regarded as an essentially random process, but the resulting somatic-cell mosaicism creates the opportunity for cell selection. In most people with red-blood-cell glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme-deficient phenotype is only moderately expressed in nucleated cells. However, in a small subset of hemizygous males who suffer from chronic nonspherocytic hemolytic anemia, the underlying mutations (designated class I) cause more-severe G6PD deficiency, and this might provide an opportunity for selection in heterozygous females during development. In order to test this possibility we have analyzed four heterozygotes for class I G6PD mutations: two with G6PD Portici (1178G{r_arrow}A) and two with G6PD Bari (1187C{r_arrow}T). We found that in fractionated blood cell types (including erythroid, myeloid, and lymphoid cell lineages) there was a significant excess of G6PD-normal cells. The significant concordance that we have observed in the degree of imbalance in the different blood-cell lineages indicates that a selective mechanism is likely to operate at the level of pluripotent blood stem cells. Thus, it appears that severe G6PD deficiency affects adversely the proliferation or the survival of nucleated blood cells and that this phenotypic characteristic is critical during hematopoiesis. 65 refs., 6 figs., 3 tabs.

  2. Impact of glucose-6-phosphate dehydrogenase deficiency on sickle cell anaemia expression in infancy and early childhood: a prospective study.

    PubMed

    Benkerrou, Malika; Alberti, Corinne; Couque, Nathalie; Haouari, Zinedine; Ba, Aissatou; Missud, Florence; Boizeau, Priscilla; Holvoet, Laurent; Ithier, Ghislaine; Elion, Jacques; Baruchel, André; Ducrocq, Rolande

    2013-12-01

    In patients with sickle cell anaemia (SCA), concomitant glucose-6-phosphate dehydrogenase (G6PD) deficiency is usually described as having no effect and only occasionally as increasing severity. We analysed sequential clinical and biological data for the first 42 months of life in SCA patients diagnosed by neonatal screening, including 27 G6PD-deficient patients, who were matched on sex, age and parents' geographic origin to 81 randomly selected patients with normal G6PD activity. In the G6PD-deficient group, steady-state haemoglobin was lower (-6·2 g/l, 95% confidence interval (CI), [-10·1; -2·3]) and reticulocyte count higher (247 × 10(9) /l, 95%CI, [97; 397]). The acute anaemic event rate was 3 times higher in the G6PD-deficient group (P < 10(-3) ). A higher proportion of G6PD-deficient patients required blood transfusion (20/27 [74%] vs. 37/81 [46%], P < 10(-3) ), for acute anaemic events, and also vaso-occlusive and infectious events. No significant between-group differences were found regarding the rates of vaso-occlusive, infectious, or cerebrovascular events. G6PD deficiency in babies with SCA worsens anaemia and increases blood transfusion requirements in the first years of life. These effects decrease after 2 years of age, presumably as the decline in fetal haemoglobin levels leads to increased sickle cell haemolysis and younger red blood cells with higher G6PD activity. © 2013 John Wiley & Sons Ltd.

  3. Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P

    2015-10-01

    The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management.

  4. Malaria, favism and glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Huheey, J E; Martin, D L

    1975-10-15

    Although glucose-6-phosphate dehydrogenase deficient individuals may suffer (sometimes fatally) from favism, a high incidence of this trait occurs in many Mediterranean populations. This apparent paradox is explained on the basis of a synergistic interaction between favism and G-6-PD deficiency that provides increased protection against malaria compared to that of the G-6-PD deficiency alone. This relationship is analogous to that between various hemoglobins and malaria in that there is selection for a more severe trait if it provides more protection against malaria.

  5. Glucose-6-Phosphate Dehydrogenase Deficiency and Physical and Mental Health until Adolescence

    PubMed Central

    Kwok, Man Ki; Leung, Gabriel M.; Schooling, C. Mary

    2016-01-01

    Background To examine the association of glucose-6-phosphate dehydrogenase (G6PD) deficiency with adolescent physical and mental health, as effects of G6PD deficiency on health are rarely reported. Methods In a population-representative Chinese birth cohort: “Children of 1997” (n = 8,327), we estimated the adjusted associations of G6PD deficiency with growth using generalized estimating equations, with pubertal onset using interval censored regression, with hospitalization using Cox proportional hazards regression and with size, blood pressure, pubertal maturation and mental health using linear regression with multiple imputation and inverse probability weighting. Results Among 5,520 screened adolescents (66% follow-up), 4.8% boys and 0.5% girls had G6PD deficiency. G6PD-deficiency was not associated with birth weight-for-gestational age or length/height gain into adolescence, but was associated with lower childhood body mass index (BMI) gain (-0.38 z-score, 95% confidence interval (CI) -0.57, -0.20), adjusted for sex and parental education, and later onset of pubic hair development (time ratio = 1.029, 95% CI 1.007, 1.050). G6PD deficiency was not associated with blood pressure, height, BMI or mental health in adolescence, nor with serious infectious morbidity until adolescence. Conclusions G6PD deficient adolescents had broadly similar physical and mental health indicators, but transiently lower BMI gain and later pubic hair development, whose long-term implications warrant investigation. PMID:27824927

  6. Evaluation of the blue formazan spot test for screening glucose 6 phosphate dehydrogenase deficiency.

    PubMed

    Pujades, A; Lewis, M; Salvati, A M; Miwa, S; Fujii, H; Zarza, R; Alvarez, R; Rull, E; Corrons, J L

    1999-06-01

    Several screening tests for glucose 6 phosphate dehydrogenase (G6PD) deficiency have been reported thus far, and a standardized method of testing was proposed by the International Council for Standardization in Hematology (ICSH). The screening test used in any particular laboratory depends upon a number of factors such as cost, time required, temperature, humidity, and availability of reagents. In this study, a direct comparison between three different G6PD screening methods has been undertaken. In 71 cases (50 hematologically normal volunteers, 9 hemizygous G6PD-deficient males, and 12 heterozygous deficient females), the blue formazan spot test (BFST) was compared with the conventional methemoglobin reduction test (HiRT) and the ICSH-recommended fluorescent spot test (FST-ICSH). In all cases, the results obtained with the three screening tests were correlated with the enzyme activity assayed spectrophotometrically. In hemizygous G6PD-deficient males, all cases were equally detected with the three methods: BFST (4.7-6.64, controls: 11.1-13.4), BMRT (score +3 in all 9 cases), and FST (no fluorescence in 9 cases). In heterozygous G6PD-deficient females, two methods detected 7 out of 12 cases (BFST: 8.71-11.75, controls: 11.1-13.4; and BMRT: score +3 in 7 cases), whereas the FST-ICSH missed all 12 cases that presented a variable degree of fluorescence. Although the sensitivity for G6PD-deficient carrier detection is the same for the BMRT and the BFST, the latter has the advantage of being semiquantitative and not merely qualitative. Unfortunately, none of the three screening tests compared here allowed the detection of the 100% heterozygote carrier state of G6PD deficiency.

  7. [Frequency of glucose-6-phosphate dehydrogenase deficiency (A-376/202) in three Malian ethnic groups].

    PubMed

    Dolo, A; Maiga, B; Guindo, A; Diakité, S A S; Diakite, M; Tapily, A; Traoré, M; Sangaré, B; Arama, C; Daou, M; Doumbo, O

    2014-08-01

    Erythrocyte G6PD deficiency is the most common worldwide enzymopathy. The aim of this study was to determine erythrocyte G6PD deficiency in 3 ethnic groups of Mali and to investigate whether erythrocyte G6PD deficiency was associated to the observed protection against malaria seen in Fulani ethnic group. The study was conducted in two different areas of Mali: in the Sahel region of Mopti where Fulani and Dogon live as sympatric ethnic groups and in the Sudanese savannah area where lives mostly the Malinke ethnic group. The study was conducted in 2007 in Koro and in 2008 in Naguilabougou. It included a total 90 Dogon, 42 Fulani and 80 Malinke ethnic groups. Malaria was diagnosed using microscopic examination after Giemsa-staining of thick and thin blood smear. G6PD deficiency (A-(376/202)) samples were identified using RFLP (Restriction Fragment Length Polymorphism) assay and analysis of PCR-amplified DNA amplicon. G6PD deficiency (A-(376/202)) rate was 11.1%, 2.4%, and 13.3% in Dogon, Fulani, and Malinke ethnic group respectively. Heterozygous state for G6PD (A-(376/202)) was found in 7.8% in Dogon; 2.4% in Fulani and 9.3% in Malinke ethnic groups while hemizygous state was found at the frequency of 2.2% in Dogon and 4% in Malinke. No homozygous state was found in our study population.We conclude that G6PD deficiency is not differing significantly between the three ethnic groups, Fulani, Dogon and Malinke.

  8. A new paper-based analytical device for detection of Glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Kaewarsa, Phuritat; Laiwattanapaisal, Wanida; Palasuwan, Attakorn; Palasuwan, Duangdao

    2017-03-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic haemolytic disorder. Most persons with G6PD deficiency are asymptomatic, but exposure to oxidant drugs, such as the anti-malarial drug primaquine, may induce haemolysis, which is commonly found in Asian countries. A reliable test is necessary for diagnosing the deficiency to prevent an acute haemolytic crisis. This study proposes a novel quantitative method to detect G6PD deficiency using paper-based analytical devices (G6PDD-PAD). Wax printing was utilized for fabricating circular reaction zone patterns in paper. The colorimetric assay is based on the formation of formazan via a reduction of tetra-nitro blue tetrazolium (TNBT) by the G6PD enzyme on G6PDD-PAD. Detection was achieved by capturing the colour using a desktop scanner and the colour intensity was analysed with Adobe Photoshop C56. The results showed that the G6PD activity analysed by G6PDD-PAD was highly correlated with the standard biochemical assay (SBA) (r(2)=0.87, p<0.01). Moreover, good agreement by Bland-Altman bias plot was demonstrated between G6PDD-PAD and the SBA (mean bias 1.4 IU/gHb). The detection limit was 0 IU/gHb of G6PD activity. This study demonstrates the feasibility of using G6PDD-PAD. This simple, low-cost test ($0.1/test) should be useful for diagnosing G6PD deficiency in resource-limited settings. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Risks of Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficient Infants Exposed to Chlorproguanil-Dapsone, Mefloquine and Sulfadoxine-Pyrimethamine as Part of Intermittent Presumptive Treatment of Malaria in Infants.

    PubMed

    Poirot, Eugenie; Vittinghoff, Eric; Ishengoma, Deus; Alifrangis, Michael; Carneiro, Ilona; Hashim, Ramadhan; Baraka, Vito; Mosha, Jacklin; Gesase, Samwel; Chandramohan, Daniel; Gosling, Roland

    2015-01-01

    Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimalarial regimens. We sought to examine the joint effects of G6PD status and IPTi antimalarial treatment on incidence of hemolysis in asymptomatic children treated with CD, sulfadoxine-pyrimethamine (SP), and mefloquine (MQ). A secondary analysis of data from a double-blind, placebo-controlled trial of IPTi was conducted. Hemoglobin (Hb) measurements were made at IPTi doses, regular follow-up and emergency visits. G6PD genotype was determined at 9 months looking for SNPs for the A- genotype at coding position 202. Multivariable linear and logistic regression models were used to examine hemolysis among children with valid G6PD genotyping results. Hemolysis was defined as the absolute change in Hb or as any post-dose Hb <8 g/dL. These outcomes were assessed using either a single follow-up Hb on day 7 after an IPTi dose or Hb obtained 1 to 14 or 28 days after each IPTi dose. Relative to placebo, CD reduced Hb by approximately 0.5 g/dL at day 7 and within 14 days of an IPTi dose, and by 0.2 g/dL within 28 days. Adjusted declines in the CD group were larger than in the MQ and SP groups. At day 7, homo-/hemizygous genotype was associated with higher odds of Hb <8 g/dL (adjusted odds ratio = 6.7, 95% CI 1.7 to 27.0) and greater absolute reductions in Hb (-0.6 g/dL, 95% CI -1.1 to 0.003). There was no evidence to suggest increased reductions in Hb among homo-/hemizygous children treated with CD compared to placebo, SP or MQ. While treatment with CD demonstrated greater reductions in Hb at 7 and 14 days after an IPTi dose compared to both SP and MQ, there was no evidence that G6PD deficiency exacerbated the adverse effects of CD, despite evidence for higher hemolysis risk among G6PDd infants.

  10. A comprehensive analysis of membrane and morphology of erythrocytes from patients with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Fang, Zishui; Jiang, Chengrui; Tang, Jia; He, Ming; Lin, Xiaoying; Chen, Xiaodan; Han, Luhao; Zhang, Zhiqiang; Feng, Yi; Guo, Yibin; Li, Hongyi; Jiang, Weiying

    2016-06-01

    Acute hemolytic anemia could be triggered by oxidative stress in the patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, the underlying hemolytic mechanism is unknown. To make clear the hemolytic mechanisms, a systematic study on membrane ultrastructure had been undertaken. A comprehensive method was used including atomic force microscopy, scanning electron microscopy, flow cytometer and fluorescence microscopy to analyze the membrane ultrastructure, externalized phosphatidylserine (PS), intracellular Ca(2+) concentration, morphology and the distributions of band 3 protein in G6PD deficient red blood cells (RBCs) after tert-butyl-hydroperoxide (t-BHP) oxidation. The results showed that erythrocyte shrinkage, annexin-V binding to externalized PS on the membrane of early-stage apoptotic cells, the increased membrane roughness and intracellular Ca(2+) concentration, as well as the change of distributions of band 3 protein in RBCs. Compared with the control RBCs, as the concentration of t-BHP up to 0.1mM, the membrane roughness of G6PD deficient RBCs showed significant difference (p<0.05) and as the concentration of t-BHP up to 0.3mM, externalized PS showed significant difference (p<0.05). Furthermore, the population types of RBCs showed dramatic difference between control groups and G6PD deficient groups. Oxidative stress induced more serious erythrocyte apoptosis and resulted in increased roughness of erythrocyte membrane and abnormal distributed band 3 protein in G6PD deficient RBCs. Echinocytes are the predominant abnormal erythrocyte shape occurring in the peripheral blood from patients with G6PD deficiency, which may shorten the RBCs lifespan. The results in the present study will give an increased understanding for the hemolytic mechanism of G6PD deficiency.

  11. Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets.

    PubMed

    Hecker, Peter A; Mapanga, Rudo F; Kimar, Charlene P; Ribeiro, Rogerio F; Brown, Bethany H; O'Connell, Kelly A; Cox, James W; Shekar, Kadambari C; Asemu, Girma; Essop, M Faadiel; Stanley, William C

    2012-10-15

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzymopathy that affects cellular redox status and may lower flux into nonoxidative pathways of glucose metabolism. Oxidative stress may worsen systemic glucose tolerance and cardiometabolic syndrome. We hypothesized that G6PD deficiency exacerbates diet-induced systemic metabolic dysfunction by increasing oxidative stress but in myocardium prevents diet-induced oxidative stress and pathology. WT and G6PD-deficient (G6PDX) mice received a standard high-starch diet, a high-fat/high-sucrose diet to induce obesity (DIO), or a high-fructose diet. After 31 wk, DIO increased adipose and body mass compared with the high-starch diet but to a greater extent in G6PDX than WT mice (24 and 20% lower, respectively). Serum free fatty acids were increased by 77% and triglycerides by 90% in G6PDX mice, but not in WT mice, by DIO and high-fructose intake. G6PD deficiency did not affect glucose tolerance or the increased insulin levels seen in WT mice. There was no diet-induced hypertension or cardiac dysfunction in either mouse strain. However, G6PD deficiency increased aconitase activity by 42% and blunted markers of nonoxidative glucose pathway activation in myocardium, including the hexosamine biosynthetic pathway activation and advanced glycation end product formation. These results reveal a complex interplay between diet-induced metabolic effects and G6PD deficiency, where G6PD deficiency decreases weight gain and hyperinsulinemia with DIO, but elevates serum free fatty acids, without affecting glucose tolerance. On the other hand, it modestly suppressed indexes of glucose flux into nonoxidative pathways in myocardium, suggesting potential protective effects.

  12. False-Positive Newborn Screen Using the Beutler Spot Assay for Galactosemia in Glucose-6-Phosphate Dehydrogenase Deficiency.

    PubMed

    Stuhrman, Grace; Perez Juanazo, Stefanie J; Crivelly, Kea; Smith, Jennifer; Andersson, Hans; Morava, Eva

    2017-01-12

    Classical galactosemia is detected through newborn screening by measuring galactose-1-phosphate uridylyltransferase (GALT) in the USA primarily via the Beutler spot assay. We report on an 18-month-old patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency that was originally diagnosed with classical galactosemia. The patient presented with elevated liver function enzymes and bilirubinemia and was immediately treated with soy-based formula. Confirmatory tests revealed deficiency of the GALT enzyme, however, full-sequencing of GALT was normal, suggestive of a different ideology. The Beutler spot assay uses three other enzymatic steps in addition to GALT. A deficiency in either of these enzymes can result in suspected decreased GALT activity when using the Beutler assay. Congenital Disorders of Glycosylation screening for phosphoglucomutase-1 deficiency was negative. Quantitative analysis of G6PD enzyme in red blood cells showed a severe deficiency and a deletion in G6PD. Soy-formula, the standard treatment for galactosemia, has been reported to trigger hemolysis in G6PD deficient patients. G6PD and phosphoglucomutase-1 deficiencies should be considered when confirmatory tests are negative for pathogenic variants in GALT and galactose-1-phosphate level is normal.

  13. Relationship between exposure to icterogenic agents, glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Nigeria.

    PubMed

    Owa, J A

    1989-11-01

    In a study of the relationship between exposure to icterogenic agents, G-6-PD deficiency and severe neonatal jaundice (NNJ) (serum bilirubin greater than or equal to 205 mumol/l) in 234 Nigerian term male neonates, 106 infants with severe NNJ and 128 controls, it was found that 62.3% of the jaundiced infants and 13.3% of the infants without NNJ were G6PD deficient (p less than 0.01). The proportion of infants exposed to icterogenic agents in the two groups was very similar (p greater than or equal to 0.5). There was a strong association between exposure to icterogenic agents and NNJ in 83 G6PD deficient infants (p less than 0.01), but there was no association between exposure to icterogenic agents and NNJ in the whole group of 234 infants or in 151 infants with normal G6PD status. It is concluded that there is an association between genetically determined G-6-PD deficiency and exogenous agents in causing severe NNJ in Nigerian infants.

  14. Single-Dose Primaquine in a Preclinical Model of Glucose-6-Phosphate Dehydrogenase Deficiency: Implications for Use in Malaria Transmission-Blocking Programs.

    PubMed

    Wickham, Kristina S; Baresel, Paul C; Marcsisin, Sean R; Sousa, Jason; Vuong, Chau T; Reichard, Gregory A; Campo, Brice; Tekwani, Babu L; Walker, Larry A; Rochford, Rosemary

    2016-10-01

    Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ. A single-dose administration of PQ was therefore assessed in our huRBC-SCID mouse model used to predict hemolytic toxicity with respect to G6PD deficiency. In this model, nonobese diabetic (NOD)/SCID mice are engrafted with human red blood cells (huRBC) from donors with the African or Mediterranean variant of G6PDd (A-G6PDd or Med-G6PDd, respectively) and demonstrate dose-dependent sensitivity to PQ. In mice engrafted with A-G6PD-deficient huRBC, single-dose PQ at 3.125, 6.25, or 12.5 mpk had no significant loss of huRBC compared to the vehicle control group. In contrast, in mice engrafted with Med-G6PDd huRBC, a single dose of PQ at 3.125, 6.25, or 12.5 mpk resulted in a significant, dose-dependent loss of huRBC compared to the value for the vehicle control group. Our data suggest that administration of a single low dose of 0.25 mpk of PQ could induce hemolytic anemia in Med-G6PDd individuals but that use of single-dose PQ at 0.25 mpk as a gametocytocidal drug to block transmission would be safe in areas where A-G6PDd predominates. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. Single-Dose Primaquine in a Preclinical Model of Glucose-6-Phosphate Dehydrogenase Deficiency: Implications for Use in Malaria Transmission-Blocking Programs

    PubMed Central

    Wickham, Kristina S.; Baresel, Paul C.; Sousa, Jason; Vuong, Chau T.; Reichard, Gregory A.; Campo, Brice; Tekwani, Babu L.; Walker, Larry A.

    2016-01-01

    Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ. A single-dose administration of PQ was therefore assessed in our huRBC-SCID mouse model used to predict hemolytic toxicity with respect to G6PD deficiency. In this model, nonobese diabetic (NOD)/SCID mice are engrafted with human red blood cells (huRBC) from donors with the African or Mediterranean variant of G6PDd (A-G6PDd or Med-G6PDd, respectively) and demonstrate dose-dependent sensitivity to PQ. In mice engrafted with A-G6PD-deficient huRBC, single-dose PQ at 3.125, 6.25, or 12.5 mpk had no significant loss of huRBC compared to the vehicle control group. In contrast, in mice engrafted with Med-G6PDd huRBC, a single dose of PQ at 3.125, 6.25, or 12.5 mpk resulted in a significant, dose-dependent loss of huRBC compared to the value for the vehicle control group. Our data suggest that administration of a single low dose of 0.25 mpk of PQ could induce hemolytic anemia in Med-G6PDd individuals but that use of single-dose PQ at 0.25 mpk as a gametocytocidal drug to block transmission would be safe in areas where A-G6PDd predominates. PMID:27458212

  16. Glucose-6-phosphate dehydrogenase deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2.

    PubMed

    Roshankhah, Shiva; Rostami-Far, Zahra; Shaveisi-Zadeh, Farhad; Movafagh, Abolfazl; Bakhtiari, Mitra; Shaveisi-Zadeh, Jila

    2016-12-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. G6PD plays a key role in the pentose phosphate pathway, which is a major source of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH provides the reducing equivalents for oxidation-reduction reductions involved in protecting against the toxicity of reactive oxygen species such as H2O2. We hypothesized that G6PD deficiency may reduce the amount of NADPH in sperms, thereby inhibiting the detoxification of H2O2, which could potentially affect their motility and viability, resulting in an increased susceptibility to infertility. Semen samples were obtained from four males with G6PD deficiency and eight healthy males as a control. In both groups, motile sperms were isolated from the seminal fluid and incubated with 0, 10, 20, 40, 60, 80, and 120 µM concentrations of H2O2. After 1 hour incubation at 37℃, sperms were evaluated for motility and viability. Incubation of sperms with 10 and 20 µM H2O2 led to very little decrease in motility and viability, but motility decreased notably in both groups in 40, 60, and 80 µM H2O2, and viability decreased in both groups in 40, 60, 80, and 120 µM H2O2. However, no statistically significant differences were found between the G6PD-deficient group and controls. G6PD deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2, and the reducing equivalents necessary for protection against H2O2 are most likely produced by other pathways. Therefore, G6PD deficiency cannot be considered as major risk factor for male infertility.

  17. Glucose-6-phosphate dehydrogenase deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2

    PubMed Central

    Roshankhah, Shiva; Rostami-Far, Zahra; Shaveisi-Zadeh, Farhad; Movafagh, Abolfazl; Shaveisi-Zadeh, Jila

    2016-01-01

    Objective Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. G6PD plays a key role in the pentose phosphate pathway, which is a major source of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH provides the reducing equivalents for oxidation-reduction reductions involved in protecting against the toxicity of reactive oxygen species such as H2O2. We hypothesized that G6PD deficiency may reduce the amount of NADPH in sperms, thereby inhibiting the detoxification of H2O2, which could potentially affect their motility and viability, resulting in an increased susceptibility to infertility. Methods Semen samples were obtained from four males with G6PD deficiency and eight healthy males as a control. In both groups, motile sperms were isolated from the seminal fluid and incubated with 0, 10, 20, 40, 60, 80, and 120 µM concentrations of H2O2. After 1 hour incubation at 37℃, sperms were evaluated for motility and viability. Results Incubation of sperms with 10 and 20 µM H2O2 led to very little decrease in motility and viability, but motility decreased notably in both groups in 40, 60, and 80 µM H2O2, and viability decreased in both groups in 40, 60, 80, and 120 µM H2O2. However, no statistically significant differences were found between the G6PD-deficient group and controls. Conclusion G6PD deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2, and the reducing equivalents necessary for protection against H2O2 are most likely produced by other pathways. Therefore, G6PD deficiency cannot be considered as major risk factor for male infertility. PMID:28090457

  18. Hereditary characteristics of enzyme deficiency and dermatoglyphics in congenital color blindness.

    PubMed

    Wu, L Z; Zeng, L H; Ma, Q Y; Xie, Y J; Chen, Y Z; Wu, D Z

    1988-01-01

    The hereditary characteristics of enzyme deficiency and dermatoglyphics in congenital color blindness (CCB) were studied. We propose that there is a linkage between the two loci on the X-chromosome determining CCB and glucose-6-phosphate dehydrogenase (G6PD), based on our study of a high incidence of G6PD deficiency in 156 male cases with CCB. The CCB gene is closely linked with that of G6PD deficiency from our pedigree investigations. The rise in the frequency of eight or more whorls, the low value of atd angle and the presenting rate of real palmar patterns of the thenar, hypothenar and I, areas presented the hereditary traits of congenital color blindness.

  19. Comparison of quantitative and qualitative tests for glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    LaRue, Nicole; Kahn, Maria; Murray, Marjorie; Leader, Brandon T; Bansil, Pooja; McGray, Sarah; Kalnoky, Michael; Zhang, Hao; Huang, Huiqiang; Jiang, Hui; Domingo, Gonzalo J

    2014-10-01

    A barrier to eliminating Plasmodium vivax malaria is inadequate treatment of infected patients. 8-Aminoquinoline-based drugs clear the parasite; however, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk for hemolysis from these drugs. Understanding the performance of G6PD deficiency tests is critical for patient safety. Two quantitative assays and two qualitative tests were evaluated. The comparison of quantitative assays gave a Pearson correlation coefficient of 0.7585 with significant difference in mean G6PD activity, highlighting the need to adhere to a single reference assay. Both qualitative tests had high sensitivity and negative predictive value at a cutoff G6PD value of 40% of normal activity if interpreted conservatively and performed under laboratory conditions. The performance of both tests dropped at a cutoff level of 45%. Cytochemical staining of specimens confirmed that heterozygous females with > 50% G6PD-deficient cells can seem normal by phenotypic tests. © The American Society of Tropical Medicine and Hygiene.

  20. Psychotic mania in glucose-6-phosphate-dehydrogenase-deficient subjects

    PubMed Central

    Bocchetta, Alberto

    2003-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with acute psychosis, catatonic schizophrenia, and bipolar disorders by previous inconclusive reports. A particularly disproportionate rate of enzyme deficiency was found in manic schizoaffective patients from 662 lithium patients surveyed in Sardinia. The purpose of this study was to describe clinical characteristics which may be potentially associated with G6PD deficiency. Methods Characteristics of episodes, course of illness, family pattern of illness, laboratory tests, and treatment response of 29 G6PD-deficient subjects with a Research Diagnostic Criteria diagnosis of manic schizoaffective disorder were abstracted from available records. Results The most peculiar pattern was that of acute recurrent psychotic manic episodes, mostly characterized by loosening of associations, agitation, catatonic symptoms, and/or transient confusion, concurrent hyperbilirubinemia, positive psychiatric family history, and partial response to long-term lithium treatment. Conclusions A relationship between psychiatric disorder and G6PD deficiency is to be searched in the bipolar spectrum, particularly among patients with a history of acute episodes with psychotic and/or catatonic symptoms or with transient confusion. PMID:12844366

  1. Antimalarial NADPH-Consuming Redox-Cyclers As Superior Glucose-6-Phosphate Dehydrogenase Deficiency Copycats

    PubMed Central

    Bielitza, Max; Belorgey, Didier; Ehrhardt, Katharina; Johann, Laure; Lanfranchi, Don Antoine; Gallo, Valentina; Schwarzer, Evelin; Mohring, Franziska; Jortzik, Esther; Williams, David L.; Becker, Katja; Arese, Paolo; Elhabiri, Mourad

    2015-01-01

    Abstract Aims: Early phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by Plasmodium falciparum were shown to protect G6PD-deficient populations from severe malaria. Here, we investigated the mechanism of a novel antimalarial series, namely 3-[substituted-benzyl]-menadiones, to understand whether these NADPH-consuming redox-cyclers, which induce oxidative stress, mimic the natural protection of G6PD deficiency. Results: We demonstrated that the key benzoylmenadione metabolite of the lead compound acts as an efficient redox-cycler in NADPH-dependent methaemoglobin reduction, leading to the continuous formation of reactive oxygen species, ferrylhaemoglobin, and subsequent haemichrome precipitation. Structure–activity relationships evidenced that both drug metabolites and haemoglobin catabolites contribute to potentiate drug effects and inhibit parasite development. Disruption of redox homeostasis by the lead benzylmenadione was specifically induced in Plasmodium falciparum parasitized erythrocytes and not in non-infected cells, and was visualized via changes in the glutathione redox potential of living parasite cytosols. Furthermore, the redox-cycler shows additive and synergistic effects in combination with compounds affecting the NADPH flux in vivo. Innovation: The lead benzylmenadione 1c is the first example of a novel redox-active agent that mimics the behavior of a falciparum parasite developing inside a G6PD-deficient red blood cell (RBC) giving rise to malaria protection, and it exerts specific additive effects that are inhibitory to parasite development, without harm for non-infected G6PD-sufficient or -deficient RBCs. Conclusion: This strategy offers an innovative perspective for the development of future antimalarial drugs for G6PD-sufficient and -deficient populations. Antioxid. Redox Signal. 22, 1337–1351. PMID:25714942

  2. Glucose-6-phosphate dehydrogenase deficiency in the Greek population of Cape Town.

    PubMed

    Bonafede, R P; Botha, M C; Beighton, P

    1984-04-07

    A sample of 250 unrelated members of the Greek community of Cape Town was studied in order to establish the prevalence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in the community. A gene frequency of 0,067 in males and a prevalence of 6,7% are estimated for this group. It is recommended that persons with G-6-PD deficiency should have access to a list of medicinal agents which have the potential for precipitating acute haemolytic crises and that they should wear Medic-Alert discs bearing information concerning the disorder.

  3. Resistance of glucose-6-phosphate dehydrogenase deficiency to malaria: effects of fava bean hydroxypyrimidine glucosides on Plasmodium falciparum growth in culture and on the phagocytosis of infected cells.

    PubMed

    Ginsburg, H; Atamna, H; Shalmiev, G; Kanaani, J; Krugliak, M

    1996-07-01

    The balanced polymorphism of glucose-6-phosphate dehydrogenase deficiency (G6PD-) is believed to have evolved through the selective pressure of malarial combined with consumption of fava beans. The implicated fava bean constituents are the hydroxypyrimidine glucosides vicine and convicine, which upon hydrolysis of their beta-O-glucosidic bond, became protein pro-oxidants. In this work we show that the glucosides inhibit the growth of Plasmodium falciparum, increase the hexose-monophosphate shunt activity and the phagocytosis of malaria-infected erythrocytes. These activities are exacerbated in the presence of beta-glucosidase, implicating their pro-oxidant aglycones in the toxic effect, and are more pronounced in infected G6PD- erythrocytes. These results suggest that G6PD- infected erythrocytes are more susceptible to phagocytic cells, and that fava bean pro-oxidants are more efficiently suppressing parasite propagation in G6PD- erythrocytes, either by directly affecting parasite growth, or by means of enhanced phagocytic elimination of infected cells. The present findings could account for the relative resistance of G6PD- bearers to falciparum malaria, and establish a link between dietary habits and malaria in the selection of the G6PD- genotype.

  4. Prevalence of glucose-6-phosphate dehydrogenase deficiency and diagnostic challenges in 1500 immigrants in Denmark examined for haemoglobinopathies.

    PubMed

    Warny, Marie; Klausen, Tobias Wirenfeldt; Petersen, Jesper; Birgens, Henrik

    2015-09-01

    Similar to the thalassaemia syndromes, glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in areas historically exposed to malaria. In the present study, we used quantitative and molecular methods to determine the prevalence of G6PD deficiency in a population of 1508 immigrants in Denmark. We found the allele frequency to be between 2.4 and 2.9% in the female immigrants. Furthermore, the mutation pattern in the studied population showed a high prevalence of the G6PD A-(202A) variant in African and African-American immigrants, a high prevalence of the G6PD Mediterranean variant in Mediterranean European and Western Asian immigrants, and substantial heterogeneity in the variants found in the Eastern Asian/Pacific immigrants. Inasmuch as many of the patients included in this investigation had various thalassaemic syndromes, we were able to evaluate the effects of the interaction between a low mean corpuscular haemoglobin (MCH) value and G6PD activity, particularly in heterozygous females. The activity level was markedly influenced by the MCH value in females with normal G6PD activity, but not in heterozygous and homozygous females. Comparison of patients with normal G6PD activity and heterozygous females indicated considerable overlap in activity levels. To help separating heterozygous females from females with wild-type genes, a DNA analysis is necessary when the female activity level is between 4.0 and 4.9 U/g hgb corresponding to 50-60% of the median activity of unaffected males.

  5. Molecular Epidemiological Survey of Glucose-6-Phosphate Dehydrogenase Deficiency and Thalassemia in Uygur and Kazak Ethnic Groups in Xinjiang, Northwest China.

    PubMed

    Han, Luhao; Su, Hai; Wu, Hao; Jiang, Weiying; Chen, Suqin

    2016-06-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency and thalassemia occur frequently in tropical and subtropical regions, while the prevalence of relationship between the two diseases in Xinjiang has not been reported. We aimed to determine the prevalence of these diseases and clarify the relationship between genotypes and phenotypes of the two diseases in the Uygur and Kazak ethnic groups in Xinjiang. We measured G6PD activity by G6PD:6PGD (glucose acid-6-phosphate dehydrogenase) ratio, identified the gene variants of G6PD and α- and β-globin genes by polymerase chain reaction (PCR)-DNA sequencing and gap-PCR and compared these variants in different ethnic groups in Xinjiang with those adjacent to it. Of the 149 subjects with molecular analysis of G6PD deficiency conducted, a higher prevalence of the combined mutations c.1311C > T/IVSXI + 93T > C and IVSXI + 93T > C, both with normal enzymatic activities, were observed in the Uygur and Kazak subjects. A case of rare mutation HBB: c.135delC [codon 44 (-C) in the heterozygous state], a heterozygous case of HBB: c.68A > G [Hb G-Taipei or β22(B4)Glu→Gly] and several common single nucleotide polymorphisms (SNPs) were found on the β-globin gene. In conclusion, G6PD deficiency with pathogenic mutations and three common α-thalassemia (α-thal) [- -(SEA), -α(3.7) (rightward), -α(4.2) (leftward)] deletions and point mutations of the α-globin gene were not detected in the present study. The average incidence of β-thalassemia (β-thal) in Uygurs was 1.45% (2/138) in Xinjiang. The polymorphisms of G6PD and β-globin genes might be useful genetic markers to trace the origin and migration of the Uygur and Kazak in Xinjiang.

  6. Should blood donors be routinely screened for glucose-6-phosphate dehydrogenase deficiency? A systematic review of clinical studies focusing on patients transfused with glucose-6-phosphate dehydrogenase-deficient red cells.

    PubMed

    Renzaho, Andre M N; Husser, Eliette; Polonsky, Michael

    2014-01-01

    The risk factors associated with the use of glucose-6-phosphate dehydrogenase (G6PD)-deficient blood in transfusion have not yet been well established. Therefore, the aim of this review was to evaluate whether whole blood from healthy G6PD-deficient donors is safe to use for transfusion. The study undertook a systematic review of English articles indexed in COCHRANE, MEDLINE, EMBASE, and CINHAL, with no date restriction up to March 2013, as well as those included in articles' reference lists and those included in Google Scholar. Inclusion criteria required that studies be randomized controlled trials, case controls, case reports, or prospective clinical series. Data were extracted following the Preferred Reporting Items for Systematic Reviews using a previously piloted form, which included fields for study design, population under study, sample size, study results, limitations, conclusions, and recommendations. The initial search identified 663 potentially relevant articles, of which only 13 studies met the inclusion criteria. The reported effects of G6PD-deficient transfused blood on neonates and children appear to be more deleterious than effects reported on adult patients. In most cases, the rise of total serum bilirubin was abnormal in infants transfused with G6PD-deficient blood from 6 hours up to 60 hours after transfusion. All studies on neonates and children, except one, recommended a routine screening for G6PD deficiency for this at-risk subpopulation because their immature hepatic function potentially makes them less able to handle any excess bilirubin load. It is difficult to make firm clinical conclusions and recommendations given the equivocal results, the lack of standardized evaluation methods to categorize red blood cell units as G6PD deficient (some of which are questionable), and the limited methodological quality and low quality of evidence. Notwithstanding these limitations, based on our review of the available literature, there is little to

  7. The risk of jaundice in glucose-6-phosphate dehydrogenase deficient babies exposed to menthol.

    PubMed

    Olowe, S A; Ransome-Kuti, O

    1980-05-01

    A major cause of neonatal morbidity and mortality in Lagos, Nigeria, is severe neonatal jaundice seen in G-6-PD deficient babies. The observation that the jaundice is more severe in outpatient than in inpatient babies suggests that its cause is exogenous. "Mentholated" powder which is commonly used in many clinics and at home to dress umbilical cords was suspected to be the offending agent. A controlled study of the effects of one of these powders was carried out on 60 consecutive G-6-PD deficient babies. In 30 of them the umbilical cords were dressed daily with the powder while the remaining half who were untreated served as controls. The treated babies developed statistically more significant jaundice than the controls. Inability of neonates to conjugate menthol in this power is probably responsible for the jaundice developed by these G-6-PD deficient babies. It is concluded that the use of menthol and/or camphor-containing commerical products on neonates be discontinued, especially in communities where the incidence of G-6-PD deficiency is high as the use of such products may be contributiing to the severity of neonatal jaundice.

  8. Screening and prevention of neonatal glucose 6-phosphate dehydrogenase deficiency in Guangzhou, China.

    PubMed

    Jiang, J; Li, B; Cao, W; Jiang, X; Jia, X; Chen, Q; Wu, J

    2014-06-09

    We aimed to summarize the results of screening protocol and prevention of neonatal glucose 6-phosphate dehydrogenase (G6PD) deficiency during a 22-year-long period to provide a basis of reference for the screening of this disease. About 1,705,569 newborn subjects in Guangzhou City were screened for this deficiency. Specimens were collected according to the conventional method of specimen acquisition for "newborn dried bloodspot screening", preserved, and inspected. The specimens were studied with fluorescent spot test and quantitative fluorescence assay. Diagnosis was performed using the modified NBTG6PD/6PGD ratio method. Bloodspot filter paper specimens were sent to the laboratory within 24 h via EMS Express, and the G6PD test was performed on the same day. The G6PD deficiency-positive rate was 4.2% in the samples screened using the fluorescent spot test, while it was 5% in case of the quantitative fluorescence assay. Neonatal screening for G6PD deficiency for 11,437 cases (6117 boys and 5320 girls) showed positive results in 481 cases. About 420 cases (318 boys and 102 girls) of G6PD deficiency were confirmed with the modified Duchenne NBT ratio method. The total detection rate was 3.7:5.2% for boys and 1.9% for girls. Quantitative fluorescence assay improved the sensitivity and detection rate. Accelerating the speed of sample delivery by using Internet network systems and ensuring online availability of screening results can aid the screening and diagnosis of this deficiency within 1 week of birth.

  9. Data on how several physiological parameters of stored red blood cells are similar in glucose 6-phosphate dehydrogenase deficient and sufficient donors.

    PubMed

    Tzounakas, Vassilis L; Kriebardis, Anastasios G; Georgatzakou, Hara T; Foudoulaki-Paparizos, Leontini E; Dzieciatkowska, Monika; Wither, Matthew J; Nemkov, Travis; Hansen, Kirk C; Papassideri, Issidora S; D'Alessandro, Angelo; Antonelou, Marianna H

    2016-09-01

    This article contains data on the variation in several physiological parameters of red blood cells (RBCs) donated by eligible glucose-6-phosphate dehydrogenase (G6PD) deficient donors during storage in standard blood bank conditions compared to control, G6PD sufficient (G6PD(+)) cells. Intracellular reactive oxygen species (ROS) generation, cell fragility and membrane exovesiculation were measured in RBCs throughout the storage period, with or without stimulation by oxidants, supplementation of N-acetylcysteine and energy depletion, following incubation of stored cells for 24 h at 37 °C. Apart from cell characteristics, the total or uric acid-dependent antioxidant capacity of the supernatant in addition to extracellular potassium concentration was determined in RBC units. Finally, procoagulant activity and protein carbonylation levels were measured in the microparticles population. Further information can be found in "Glucose 6-phosphate dehydrogenase deficient subjects may be better "storers" than donors of red blood cells" [1].

  10. 46 CFR 287.25 - Assessment and collection of deficiencies.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Assessment and collection of deficiencies. 287.25 Section 287.25 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING... deficiency will run from the date the withdrawal or noncompliance occurs. The amount of any deficiency...

  11. 46 CFR 287.25 - Assessment and collection of deficiencies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Assessment and collection of deficiencies. 287.25 Section 287.25 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING... deficiency will run from the date the withdrawal or noncompliance occurs. The amount of any deficiency...

  12. 46 CFR 287.25 - Assessment and collection of deficiencies.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Assessment and collection of deficiencies. 287.25 Section 287.25 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING... deficiency will run from the date the withdrawal or noncompliance occurs. The amount of any deficiency...

  13. Prevalence of anemia, iron deficiency, thalassemia and glucose-6-phosphate dehydrogenase deficiency among hill-tribe school children in Omkoi District, Chiang Mai Province, Thailand.

    PubMed

    Yanola, Jintana; Kongpan, Chatpat; Pornprasert, Sakorn

    2014-07-01

    The prevalaence of anemia, iron deficiency, thalassemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were examined among 265 hill-tribe school children, 8-14 years of age, from Omkoi District, Chiang Mai Province, Thailand. Anemia was observed in 20 school children, of whom 3 had iron deficiency anemia. The prevalence of G-6-PD deficiency and β-thalassemia trait [codon 17 (A>T), IVSI-nt1 (G>T) and codons 71/72 (+A) mutations] was 4% and 8%, respectively. There was one Hb E trait, and no α-thalassemia-1 SEA or Thai type deletion. Furthermore, anemia was found to be associated with β-thalassemia trait in 11 children. These data can be useful for providing appropriate prevention and control of anemia in this region of Thailand.

  14. Biochemical Assessment of Coenzyme Q10 Deficiency.

    PubMed

    Rodríguez-Aguilera, Juan Carlos; Cortés, Ana Belén; Fernández-Ayala, Daniel J M; Navas, Plácido

    2017-03-05

    Coenzyme Q10 (CoQ10) deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ10 biosynthesis. Mutations in any of these genes are responsible for the primary CoQ10 deficiency, but there are also different conditions that induce secondary CoQ10 deficiency including mitochondrial DNA (mtDNA) depletion and mutations in genes involved in the fatty acid β-oxidation pathway. The diagnosis of CoQ10 deficiencies is determined by the decrease of its content in skeletal muscle and/or dermal skin fibroblasts. Dietary CoQ10 supplementation is the only available treatment for these deficiencies that require a rapid and distinct diagnosis. Here we review methods for determining CoQ10 content by HPLC separation and identification using alternative approaches including electrochemical detection and mass spectrometry. Also, we review procedures to determine the CoQ10 biosynthesis rate using labeled precursors.

  15. Biochemical Assessment of Coenzyme Q10 Deficiency

    PubMed Central

    Rodríguez-Aguilera, Juan Carlos; Cortés, Ana Belén; Fernández-Ayala, Daniel J. M.; Navas, Plácido

    2017-01-01

    Coenzyme Q10 (CoQ10) deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ10 biosynthesis. Mutations in any of these genes are responsible for the primary CoQ10 deficiency, but there are also different conditions that induce secondary CoQ10 deficiency including mitochondrial DNA (mtDNA) depletion and mutations in genes involved in the fatty acid β-oxidation pathway. The diagnosis of CoQ10 deficiencies is determined by the decrease of its content in skeletal muscle and/or dermal skin fibroblasts. Dietary CoQ10 supplementation is the only available treatment for these deficiencies that require a rapid and distinct diagnosis. Here we review methods for determining CoQ10 content by HPLC separation and identification using alternative approaches including electrochemical detection and mass spectrometry. Also, we review procedures to determine the CoQ10 biosynthesis rate using labeled precursors. PMID:28273876

  16. Red blood cell indices and prevalence of hemoglobinopathies and glucose 6 phosphate dehydrogenase deficiencies in male Tanzanian residents of Dar es Salaam.

    PubMed

    Mwakasungula, Solomon; Schindler, Tobias; Jongo, Said; Moreno, Elena; Kamaka, Kasimu; Mohammed, Mgeni; Joseph, Selina; Rashid, Ramla; Athuman, Thabit; Tumbo, Anneth Mwasi; Hamad, Ali; Lweno, Omar; Tanner, Marcel; Shekalaghe, Seif; Daubenberger, Claudia A

    2014-01-01

    Hemoglobinopathies, disorders of hemoglobin structure and production, are one of the most common monogenic disorders in humans. Glucose 6 phosphate dehydrogenase deficiency (G6PD) is an inherited enzymopathy resulting in increased oxygen stress susceptibility of red blood cells. The distributions of these genetic traits in populations living in tropical and subtropical regions where malaria has been or is still present are thought to result from survival advantage against severe life threatening malaria disease. 384 male Tanzanian volunteers residing in Dar es Salaam were typed for G6PD, sickle cell disease and α-thalassemia. The most prominent red blood cell polymorphism was heterozygous α(+)-thalassemia (37.8%), followed by the G6PD(A) deficiency (16.4%), heterozygous sickle cell trait (15.9%), G6PD(A-) deficiency (13.5%) and homozygous α(+)-thalassemia (5.2%). 35%, 45%, 17% and 3% of these volunteers were carriers of wild type gene loci, one, two or three of these hemoglobinopathies, respectively. We find that using a cut off value of 28.6 pg. for mean corpuscular hemoglobin (MCH), heterozygous α(+)-thalassemia can be predicted with a sensitivity of 84% and specificity of 72% in this male population. All subjects carrying homozygous α(+)-thalassemia were identified based on their MCH value < 28.6 pg.

  17. Ischaemic Priapism and Glucose-6-Phosphate Dehydrogenase Deficiency: A Mechanism of Increased Oxidative Stress?

    PubMed

    Morrison, B F; Thompson, E B; Shah, S D; Wharfe, G H

    2014-07-03

    Ischaemic priapism is a devastating urological condition that has the potential to cause permanent erectile dysfunction. The disorder has been associated with numerous medical conditions and the use of pharmacotherapeutic agents. The aetiology is idiopathic in a number of cases. There are two prior case reports of the association of ischaemic priapism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report on a third case of priapism associated with G6PD deficiency and review recently described molecular mechanisms of increased oxidative stress in the pathophysiology of ischaemic priapism. The case report of a 32-year old Afro-Caribbean male with his first episode of major ischaemic priapism is described. Screening for common causes of ischaemic priapism, including sickle cell disease was negative. Glucose-6-phosphate dehydrogenase deficiency was discovered on evaluation for priapism. Penile aspiration was performed and erectile function was good post treatment.Glucose-6-phosphate dehydrogenase deficiency is a cause for ischaemic priapism and should be a part of the screening process in idiopathic causes of the disorder. Increased oxidative stress occurs in G6PD deficiency and may lead to priapism.

  18. Priapism and glucose-6-phosphate dehydrogenase deficiency: An underestimated correlation?

    PubMed

    De Rose, Aldo Franco; Mantica, Guglielmo; Tosi, Mattia; Bovio, Giulio; Terrone, Carlo

    2016-10-05

    Priapism is a rare clinical condition characterized by a persistent erection unrelated to sexual excitement. Often the etiology is idiopathic. Three cases of priapism in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients have been described in literature. We present the case of a 39-year-old man with glucose- 6-phosphate dehydrogenase deficiency, who reached out to our department for the arising of a non-ischemic priapism without arteriolacunar fistula. We suggest that the glucose-6-phosphate dehydrogenase deficiency could be an underestimated risk factor for priapism.

  19. Assessment of insulin sensitivity in glucokinase-deficient subjects.

    PubMed

    Clément, K; Pueyo, M E; Vaxillaire, M; Rakotoambinina, B; Thuillier, F; Passa, P; Froguel, P; Robert, J J; Velho, G

    1996-01-01

    The chronic hyperglycaemia of glucokinase-deficient diabetes results from a glucose-sensing defect in pancreatic beta cells and abnormal hepatic glucose phosphorylation. We have evaluated the contribution of insulin resistance to this form of chronic hyperglycaemia. Insulin sensitivity, assessed by the homeostasis model assessment (HOMA) method in 35 kindreds with glucokinase mutations, was found to be significantly decreased in 125 glucokinase-deficient subjects as compared to 141 unaffected first-degree relatives. Logistic regression analysis showed that in glucokinase-deficient subjects a decrease in insulin sensitivity was associated with deterioration of the glucose tolerance status. A euglycaemic hyperinsulinaemic clamp was performed in 14 glucokinase-deficient subjects and 12 unrelated control subjects. In six patients and six control subjects the clamp was coupled to dideutero-glucose infusion to measure glucose turnover. Average glucose infusion rates (GIR) at 1 and 5 mU.kg body weight.min-1 insulin infusion rates were significantly lower in (the glucokinase-deficient) patients than in control subjects. Although heterogeneous results were observed, in 8 out of the 14 patients GIRs throughout the experiment were lower than 1 SD below the mean of the control subjects. Hepatic glucose production at 1 mU.kg body weight-1.min-1 insulin-infusion rate was significantly higher in patients than in control subjects. In conclusion, insulin resistance correlates with the deterioration of glucose tolerance and contributes to the hyperglycaemia of glucokinase-deficient diabetes. Taken together, our results are most consistent with insulin resistance being considered secondary to the chronic hyperglycaemia and/or hypoinsulinaemia of glucokinase-deficiency. Insulin resistance might also result from interactions between the unbalanced glucose metabolism and susceptibility gene(s) to low insulin sensitivity likely to be present in this population.

  20. Chloroamphenicol-Induced Hemolysis in Caucasian Glucose-6-Phosphate Dehydrogenase Deficiency

    DTIC Science & Technology

    typhoid fever with chloramphenicol. Two of these patients were studied when free of infection to determine the hemolytic potential of chloramphenicol in the noninfected G6PD-deficient white person. It was found to be mildly hemolytic under these conditions, suggesting that a drug- disease synergism was primarily responsible for the clinical hemolytic reactions. The febrile state itself, or changes in plasma amino acids accompanying infection, may be responsible for disease-related

  1. Glucose-6-phosphate dehydrogenase deficiency among malaria suspects attending Gambella hospital, southwest Ethiopia.

    PubMed

    Tsegaye, Arega; Golassa, Lemu; Mamo, Hassen; Erko, Berhanu

    2014-11-18

    Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is widespread across malaria endemic regions. G6PD-deficient individuals are at risk of haemolysis when exposed, among other agents, to primaquine and tafenoquine, which are capable of blocking malaria transmission by killing Plasmodium falciparum gametocytes and preventing Plasmodium vivax relapses by targeting hypnozoites. It is evident that no measures are currently in place to ensure safe delivery of these drugs within the context of G6PDd risk. Thus, determining G6PDd prevalence in malarious areas would contribute towards avoiding possible complications in malaria elimination using the drugs. This study, therefore, was aimed at determining G6PDd prevalence in Gambella hospital, southwest Ethiopia, using CareStart™ G6PDd fluorescence spot test. Venous blood samples were collected from febrile patients (n = 449) attending Gambella hospital in November-December 2013. Malaria was diagnosed using blood films and G6PDd was screened using CareStart™ G6PDd screening test (Access Bio, New Jersey, USA). Haematological parameters were also measured. The association of G6PD phenotype with sex, ethnic group and malaria smear positivity was tested. Malaria prevalence was 59.2% (96.6% of the cases being P. falciparum mono infections). Totally 33 participants (7.3%) were G6PD-deficient with no significant difference between the sexes. The chance of being G6PD-deficient was significantly higher for the native ethnic groups (Anuak and Nuer) compared to the 'highlanders'/settlers (odds ratio (OD) = 3.9, 95% confidence interval (CI) 0.481-31.418 for Anuak vs 'highlanders'; OD = 4.9, 95% CI 0.635-38.00 for Nuer vs 'highlanders'). G6PDd prevalence among the Nuer (14.3%) was significantly higher than that for the Anuak (12.0%). G6PDd prevalence in the area is substantial with 30 (90.9%) of the 33 deficient individuals having malaria suggesting the non-protective role of the disorder at least from clinical malaria

  2. A hemolysis trigger in glucose-6-phosphate dehydrogenase enzyme deficiency. Vicia sativa (Vetch).

    PubMed

    Bicakci, Zafer

    2009-02-01

    Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme, playing an important role in the redox metabolism of all aerobic cells. It was reported that certain medications, fava beans, and infections can trigger acute hemolytic anemia in patients with G6PD deficiency. An 8-year-old male patient was admitted to the hospital with blood in the urine, headache, dizziness, fatigue, loss of appetite, and jaundice in the eyes, 24 hours after eating large amounts of fresh, vetch grains. Laboratory investigation revealed hemolytic anemia, hyperbilirubinemia, and G6PD deficiency. Approximately 0.5% of fava bean seeds have 2 pyrimidine beta-glycosides called, vicine and convicine. Vetch has 0.731% vicine, 0.081% convicine, and 0.530% beta cyanoalanine glycosides. The aim of this case report is to emphasize the importance of vetch seeds as a cause for hemolytic crisis in our country, where approximately one million tons of vetch is produced per year, especially in the agricultural regions.

  3. Laboratory and genetic assessment of iron deficiency in blood donors.

    PubMed

    Kiss, Joseph E

    2015-03-01

    More than 9 million individuals donate blood annually in the United States. Between 200 and 250 mg of iron is removed with each whole blood donation, reflecting losses from the hemoglobin in red blood cells. Replenishment of iron stores takes many months, leading to a high rate of iron depletion. In an effort to better identify and prevent iron deficiency, blood collection centers are now considering various strategies to manage donor iron loss. This article highlights laboratory and genetic tests to assess the iron status of blood donors and their applicability as screening tests for blood donation. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Glucose-6-phosphate dehydrogenase deficiency in people living in malaria endemic districts of Nepal.

    PubMed

    Ghimire, Prakash; Singh, Nihal; Ortega, Leonard; Rijal, Komal Raj; Adhikari, Bipin; Thakur, Garib Das; Marasini, Baburam

    2017-05-23

    Glucose-6-phosphate dehydrogenase (G6PD) is a rate limiting enzyme of the pentose phosphate pathway and is closely associated with the haemolytic disorders among patients receiving anti-malarial drugs, such as primaquine. G6PD deficiency (G6PDd) is an impending factor for radical treatment of malaria which affects the clearance of gametocytes from the blood and subsequent delay in the achievement of malaria elimination. The main objective of this study was to assess the prevalence of G6PD deficiency in six malaria endemic districts in Southern Nepal. A cross-sectional population based prevalence survey was conducted in six malaria endemic districts of Nepal, during April-Dec 2013. A total of 1341 blood samples were tested for G6PDd using two different rapid diagnostic test kits (Binax-Now(®) and Care Start™). Equal proportions of participants from each district (n ≥ 200) were enrolled considering ethnic and demographic representation of the population groups. Out of total 1341 blood specimens collected from six districts, the overall prevalence of G6PDd was 97/1341; 7.23% on Binax Now and 81/1341; 6.0% on Care Start test. Higher prevalence was observed in male than females [Binax Now: male 10.2%; 53/521 versus female 5.4%; 44/820 (p = 0.003) and Care Start: male 8.4%; 44/521 versus female 4.5%; 37/820 (p = 0.003)]. G6PDd was higher in ethnic groups Rajbanshi (11.7%; 19/162) and Tharu (5.6%; 56/1005) (p = 0.006), major inhabitant of the endemic districts. Higher prevalence of G6PDd was found in Jhapa (22/224; 9.8%) and Morang districts (18/225; 8%) (p = 0.031). In a multivariate analysis, male were found at more risk for G6PDd than females, on Binax test (aOR = 1.97; CI 1.28-3.03; p = 0.002) and Care Start test (aOR = 1.86; CI 1.16-2.97; p = 0.009). The higher prevalence of G6PDd in certain ethnic group, gender and geographical region clearly demonstrates clustering of the cases and ascertained the risk groups within the population. This is

  5. Inherited Glutathione Reductase Deficiency and Plasmodium falciparum Malaria—A Case Study

    PubMed Central

    Rahlfs, Stefan; Schirmer, R. Heiner; van Zwieten, Rob; Roos, Dirk; Arese, Paolo; Becker, Katja

    2009-01-01

    In Plasmodium falciparum-infected red blood cells (RBCs), the flavoenzyme glutathione reductase (GR) regenerates reduced glutathione, which is essential for antioxidant defense. GR utilizes NADPH produced in the pentose phosphate shunt by glucose-6-phosphate dehydrogenase (G6PD). Thus, conditions affecting host G6PD or GR induce increased sensitivity to oxidants. Hereditary G6PD deficiency is frequent in malaria endemic areas and provides protection against severe malaria. Furthermore, GR deficiency resulting from insufficient saturation of the enzyme with its prosthetic group FAD is common. Based on these naturally occurring phenomena, GR of malaria parasites and their host cells represent attractive antimalarial drug targets. Recently we were given the opportunity to examine invasion, growth, and drug sensitivity of three P. falciparum strains (3D7, K1, and Palo Alto) in the RBCs from three homozygous individuals with total GR deficiency resulting from mutations in the apoprotein. Invasion or growth in the GR-deficient RBCs was not impaired for any of the parasite strains tested. Drug sensitivity to chloroquine, artemisinin, and methylene blue was comparable to parasites grown in GR-sufficient RBCs and sensitivity towards paraquat and sodium nitroprusside was only slightly enhanced. In contrast, membrane deposition of hemichromes as well as the opsonizing complement C3b fragments and phagocytosis were strongly increased in ring-infected RBCs of the GR-deficient individuals compared to ring-infected normal RBCs. Also, in one of the individuals, membrane-bound autologous IgGs were significantly enhanced. Thus, based on our in vitro data, GR deficiency and drug-induced GR inhibition may protect from malaria by inducing enhanced ring stage phagocytosis rather than by impairing parasite growth directly. PMID:19806191

  6. Increased red cell calcium, decreased calcium adenosine triphosphatase, and altered membrane proteins during fava bean hemolysis in glucose-6-phosphate dehydrogenase-deficient (Mediterranean variant) individuals.

    PubMed

    Turrini, F; Naitana, A; Mannuzzu, L; Pescarmona, G; Arese, P

    1985-08-01

    RBCs from four glucose-6-phosphate dehydrogenase (G6PD)-deficient (Mediterranean variant) subjects were studied during fava bean hemolysis. In the density-fractionated RBC calcium level, Ca2+-ATPase activity, reduced glutathione level, and ghost protein pattern were studied. In the bottom fraction, containing most heavily damaged RBCs, calcium level ranged from 143 to 244 mumol/L RBCs (healthy G6PD-deficient controls: 17 +/- 5 mumol/L RBCs). The Ca2+-ATPase activity ranged from 0.87 to 1.84 mumol ATP consumed/g Hb/min (healthy G6PD-deficient controls: 2.27 +/- 0.4). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of ghosts showed: (1) the presence of high mol wt aggregates (in three cases they were reduced by dithioerythritol; in one case, only partial reduction was possible); (2) the presence of multiple, scattered new bands; and (3) the reduction of band 3. Oxidant-mediated damage to active calcium extrusion, hypothetically associated with increased calcium permeability, may explain the large increase in calcium levels. They, in turn, could activate calcium-dependent protease activity, giving rise to the profound changes in the ghost protein pattern.

  7. [Frequency of color blindness and glucose-6-phosphate dehydrogenase enzyme deficiency in non-industrialized populations in the state of Nuevo León, México].

    PubMed

    Ceda-Flores, R M; Arriaga-Ríos, G; Muñoz-Campos, J; Bautista-Peña, V A; Angeles Rojas-Alvarado, M; González-Quiróga, G; Leal-Garza, C H; Garza-Chapa, R

    1990-01-01

    In order to know if there would be genetic structural differences among non industrial and industrial populations, two genetic markers were studied: color-blindness (CPC) and glucose-6-phosphate dehydrogenase deficiency (G6PD), in students, males and females that were resident in five non industrial populations in the State of Nuevo Leon. The results were compared with the information for industrial zone from the Monterrey Metropolitan area (AMM). It was found that the frequencies of CPC and G6PD in non industrial populations (2.57 and 0.00 per cent), were lower than the ones in the industrial AMM (4.0 and 0.66 per cent), probably as a result that in the first populations, with minor urbanization, the main factors that influence are: natural selection, interacial mixed or genetic drift and the second population is the immigration, since 1940 to present time, of Mexican populations with greater influence from the Indians and Africans.

  8. Laboratory and Genetic Assessment of Iron Deficiency in Blood Donors

    PubMed Central

    Kiss, Joseph E.

    2015-01-01

    Synopsis Over 9 million individuals donate blood annually in the US. Between 200 to 250 mg of iron is removed with each whole blood donation, reflecting losses from the hemoglobin in red blood cells. This amount represents approximately 25% of the average iron stores in men and almost 75% of the iron stores in women. Replenishment of iron stores takes many months, leading to a high rate of iron depletion, especially in frequent blood donors (e. g., more than 2 times per year). In large epidemiologic studies, donation frequency, female gender, and younger age (reflecting menstrual status), are particularly associated with iron depletion. Currently, a minimum capillary hemoglobin of 12.5 gm/dl is the sole requirement for donor qualification in the US as far as iron levels are concerned, yet it is known that hemoglobin level is a poor surrogate for low iron. In an effort to better identify and prevent iron deficiency, blood collection centers are now considering various strategies to manage donor iron loss, including changes in acceptable hemoglobin level, donation interval, donation frequency, testing of iron status, and iron supplementation. This chapter highlights laboratory and genetic tests to assess the iron status of blood donors and their applicability as screening tests for blood donation. PMID:25676373

  9. Assessment of subjective sleep quality in iron deficiency anaemia.

    PubMed

    Murat, Semiz; Ali, Uslu; Serdal, Korkmaz; Süleyman, Demir; İlknur, Parlak; Mehmet, Sencan; Bahattin, Aydın; Tunahan, Uncu

    2015-06-01

    We aimed to assess the effect of anemia on subjective sleep quality in patients with iron deficiency anemia (IDA). One hundred and four patients diagnosed with IDA and 80 healthy individuals, who are gender and age matched, were included in the study. All participants were requested to fill 3 forms: a socio-demographic form (age, gender, marital status, income level and educational status), hospital anxiety and depression (HAD) scale and pittsburgh sleep quality index (PSQI). According to the HAD scale, the average anxiety score was found 9.24±4.37 in patients and 7.58± 4.07 in controls. And, the average depression score was 7.53±4.10 in patients and 6.41±2.74 in controls. The total sleep quality score was 6.71±3.02 in patients and 4.11±1.64 in controls. There was a statistically significant difference in terms of anxiety, depression and sleep quality scores. Linear regression analysis showed no association between anxiety and depression with poor sleeping. IDA affects sleep quality irrespective of psychological symptoms such as depression and anxiety.

  10. [Hygienic assessment of iodine deficiency in the Khabarovsk Territory].

    PubMed

    Driutskaia, S M; Riabkova, V A

    2004-01-01

    Iodine deficiency is one of the most common non-communicable human diseases. The Khabarovsk Territory is among the regions affected by this condition. A complex evaluation was made of the content of iodine in the environment (water, soil), foodstuffs, and the population in the Khabarovsk Territory. By keeping in mind its great extent from north to south, Khabarovsk Territory has been divided into three areas: northern, central, and southern, by taking into account their climatic, soil, and environmental conditions. The population of the northern area of the Territory was found to be at the highest risk of iodine deficiency since the content of iodine in the foodstuffs, water, and soil was the least. The native population of the Amyr Region is more resistant to iodine deficiency than non-indigenous groups. The children of the Territory are at higher risk for iodine deficiency-associated conditions. A comprehensive study of the levels of iodine in the foodstuffs, environmental objects, and population has revealed that the Khabarovsk Territory is endemic in iodine deficiency, and its population has mild to moderate iodine deficiency.

  11. Prevalence of thalassaemia, iron-deficiency anaemia and glucose-6-phosphate dehydrogenase deficiency among Arab migrating nomad children, southern Islamic Republic of Iran.

    PubMed

    Pasalar, M; Mehrabani, D; Afrasiabi, A; Mehravar, Z; Reyhani, I; Hamidi, R; Karimi, M

    2014-12-17

    This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and β-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged < 18 years (51 males, 83 females). Low serum ferritin (< 12 ng/dL) was present in 17.9% of children (21.7% in females and 11.8% in males). Low haemoglobin (Hb) correlated significantly with a low serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had HbA2 ≥ 3.5 g/dL, indicating β-thalassaemia trait (10.8% in females and 7.8% in males). Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females. Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of β-thalassaemia trait was the major potential risk factor in this population.

  12. Dental Considerations in Children with Glucose-6-phosphate Dehydrogenase Deficiency (Favism): A Review of the Literature and Case Report.

    PubMed

    Hernández-Pérez, Daniela; Butrón-Téllez Girón, Claudia; Ruiz-Rodríguez, Socorro; Garrocho-Rangel, Arturo; Pozos-Guillén, Amaury

    2015-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an uncommon inherited enzyme deficiency characterized by hemolytic anemia, caused by the inability of erythrocytes to detoxify oxidizing agents such as drugs, infectious diseases, or fava bean ingestion. In this later case, the disorder is known as favism. The aim of the present report was to present a review of the literature in this disease, to describe a case report concerning an affected 9-year-old male, and to review the main implications and precautions in pediatric dental management.

  13. Dental Considerations in Children with Glucose-6-phosphate Dehydrogenase Deficiency (Favism): A Review of the Literature and Case Report

    PubMed Central

    Hernández-Pérez, Daniela; Butrón-Téllez Girón, Claudia; Ruiz-Rodríguez, Socorro; Garrocho-Rangel, Arturo; Pozos-Guillén, Amaury

    2015-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an uncommon inherited enzyme deficiency characterized by hemolytic anemia, caused by the inability of erythrocytes to detoxify oxidizing agents such as drugs, infectious diseases, or fava bean ingestion. In this later case, the disorder is known as favism. The aim of the present report was to present a review of the literature in this disease, to describe a case report concerning an affected 9-year-old male, and to review the main implications and precautions in pediatric dental management. PMID:26435857

  14. Rasch Measurement in the Assessment of Growth Hormone Deficiency in Adult Patients.

    ERIC Educational Resources Information Center

    Prieto, Luis; Roset, Montse; Badia, Xavier

    2001-01-01

    Tested the metric properties of a Spanish version of the Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire through Rasch analysis with a sample of 356 adult patients in Spain. Results suggest that the Spanish AGHDA could be a useful complement of the clinical evaluation of growth hormone deficiency patients at group and…

  15. Responses to Deficiencies and Suggestions, AIHA Site Assessment July 12-14, 2016

    SciTech Connect

    Bennett, Jack T.; Harding, Ruth N.

    2016-08-11

    These are the responses to the deficiencies and suggestions found during the American Industrial Hygiene Association external site assessment carried out July 12-14, 2016 in the Analytical Services and Instrumentation Division Analytical Laboratory.

  16. The assessment of frequency of iron deficiency in athletes from the transferrin receptor-ferritin index.

    PubMed

    Malczewska, J; Szczepańska, B; Stupnicki, R; Sendecki, W

    2001-03-01

    The transferrin receptor-ferritin index (sTfR/logFerr) was determined in 131 male and 121 female athletes in order to assess the frequency of iron deficiency (threshold value of that index taken as 1.8). Blood was drawn for determining morphological indices as well as sTfR, ferritin, iron, total iron binding capacity (TIBC), and haptoglobin. A significantly (p <.01) higher incidence of iron deficiency was observed in women (26%) than in men (11%). The iron deficiency was latent, since no subject was found to be anemic. The plasma iron was significantly lower and TIBC higher (p <.001) in both iron-deficient subgroups than in the non-deficient ones. This confirmed the latent character of iron deficiency. Some hematological indices (Hb, MCH, MCHC, MCV) were significantly lower in iron-deficient female athletes than in male athletes, which suggested a more profound iron deficiency in the former. The sTfR/logFerr index might thus be useful in detecting iron deficiency in athletes, especially in those with erythropoiesis disorders, since physical loads may affect the widely used ferritin levels.

  17. Glucose-6-phosphate dehydrogenase deficiency: the added value of cytology.

    PubMed

    Roelens, Marie; Dossier, Claire; Fenneteau, Odile; Couque, Nathalie; Da Costa, Lydie

    2016-06-01

    We report the case of a 2 year-old boy hospitalized into the emergency room for influenza pneumonia infection. The evolution was marked by a respiratory distress syndrome, a severe hemolytic anemia, associated with thrombocytopenia and kidney failure. First, a diagnosis of hemolytic uremic syndrome (HUS) has been judiciously suggested due to the classical triad: kidney failure, hemolytic anemia and thrombocytopenia. But, strikingly, blood smears do not exhibit schizocytes, but instead ghosts and hemighosts, some characteristic features of a glucose-6-phosphate dehydrogenase deficiency. Our hypothesis has been confirmed by enzymatic dosage and molecular biology. The unusual initial aplastic feature of this anemia could be the result of a transient erythroblastopenia due to the viral agent, at the origin of the G6PD crisis on a background of a major erythrocyte anti-oxydant enzyme defect. This case of G6PD defect points out the continuously importance of the cytology, which was able to redirect the diagnosis by the hemighost and ghost detection.

  18. Calcium-deficiency assessment and biomarker identification by an integrated urinary metabonomics analysis

    PubMed Central

    2013-01-01

    Background Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. Methods The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. Results Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson

  19. Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis

    PubMed Central

    Huang, Yang-Yang; Huang, Ching-Shui; Yang, Sien-Sing; Lin, Min-Shung; Huang, May-Jen; Huang, Ching-Shan

    2005-01-01

    AIM: To test the hypothesis that the variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis. METHODS: A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency. RESULTS: Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A(TA)6 TAA/A(TA)7TAA (6/7), heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene (P = 0.012, χ2 test), but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia (2.7% vs 2.4% and 5.1% vs 5.1%, respectively). The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog (18.0 ± 6.5 and 12.7 ± 2.9 μmol/L, respectively; P<0.001, Student’s t test). CONCLUSION: Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese. PMID:16237771

  20. Hereditary sideroblastic anemia and glucose-6-phosphate dehydrogenase deficiency in a Negro family.

    PubMed

    Prasad, A S; Tranchida, L; Konno, E T; Berman, L; Albert, S; Sing, C F; Brewer, G J

    1968-06-01

    Detailed clinical and genetic studies have been performed in a Negro family, which segregated for sex-linked sideroblastic anemia and glucose-6-phosphate dehydrogenase (G-6-DP) deficiency. This is the first such pedigree reported. Males affected with sideroblastic anemia had growth retardation, hypochromic microcytic anemia, elevated serum iron, decreased unsaturated iron-binding capacity, increased (59)Fe clearance, low (59)Fe incorporation into erythrocytes, normal erythrocyte survival ((51)Cr), normal hemoglobin electrophoretic pattern, erythroblastic hyperplasia of marrow with increased iron, and marked increase in marrow sideroblasts, particularly ringed sideroblasts. Perinuclear deposition of ferric aggregates was demonstrated to be intramitochondrial by electron microscopy. Female carriers of the sideroblastic gene were normal but exhibited a dimorphic population of erythrocytes including normocytic and microcytic cells. The bone marrow studies in the female (mother) showed ringed marrow sideroblasts. Studies of G-6-PD involved the methemoglobin elution test for G-6-PD activity of individual erythrocytes, quantitative G-6-PD assay, and electrophoresis. In the pedigree, linkage information was obtained from a doubly heterozygous woman, four of her sons, and five of her daughters. Three sons were doubly affected, and one was normal. One daughter appeared to be a recombinant. The genes appeared to be linked in the coupling phase in the mother. The maximum likelihood estimate of the recombination value was 0.14. By means of Price-Jones curves, the microcytic red cells in peripheral blood were quantitated in female carriers. The sideroblast count in the bone marrow in the mother corresponded closely to the percentage of microcytic cells in peripheral blood. This is the second example in which the cellular expression of a sex-linked trait has been documented in the human red cells, the first one being G-6-PD deficiency. The coexistence of the two genes in doubly

  1. Utilization of nutrition-focused physical assessment in identifying micronutrient deficiencies.

    PubMed

    Esper, Dema Halasa

    2015-04-01

    Heightened interest in and utilization of parts of the nutrition-focused physical assessment (NFPA) have increased with recent guidelines in defining malnutrition and the call to awareness among healthcare practitioners to recognize, document, and intervene in malnourished patients. Furthermore, an increased prevalence of nutrient deficiencies has been reported in surgical weight loss patients, those with various acute and chronic diseases, and the elderly requiring physical assessment and examination skills to identify these deficiencies. The registered dietitian nutritionist (RDN) can use the NFPA to note physical findings to use along with the other domains in the nutrition assessment to determine the nutrition-related diagnosis, while other nutrition professionals can use the NFPA findings to determine a differential diagnosis. This article outlines the NFPA and how to determine physical findings related to micronutrient deficiencies, which can have a profound impact on overall nutrition status.

  2. Quantile hydrologic model selection and model structure deficiency assessment: 2. Applications

    NASA Astrophysics Data System (ADS)

    Pande, Saket

    2013-09-01

    Quantile hydrologic model selection and structure deficiency assessment is applied in three case studies. The performance of quantile model selection problem is rigorously evaluated using a model structure on the French Broad river basin data set. The case study shows that quantile model selection encompasses model selection strategies based on summary statistics and that it is equivalent to maximum likelihood estimation under certain likelihood functions. It also shows that quantile model predictions are fairly robust. The second case study is of a parsimonious hydrological model for dry land areas in Western India. The case study shows that an intuitive improvement in the model structure leads to reductions in asymmetric loss function values for all considered quantiles. The asymmetric loss function is a quantile specific metric that is minimized to obtain a quantile specific prediction model. The case study provides evidence that a quantile-wise reduction in the asymmetric loss function is a robust indicator of model structure improvement. Finally a case study of modeling daily streamflow for the Guadalupe River basin is presented. A model structure that is least deficient for the study area is identified from nine different model structures based on quantile structural deficiency assessment. The nine model structures differ in interception, routing, overland flow and base flow conceptualizations. The three case studies suggest that quantile model selection and deficiency assessment provides a robust mechanism to compare deficiencies of different model structures and helps to identify better model structures. In addition to its novelty, quantile hydrologic model selection is a frequentist approach that seeks to complement existing Bayesian approaches to hydrological model uncertainty.

  3. Utility of geriatric assessment tools to identify 85-years old subjects with vitamin D deficiency.

    PubMed

    Formiga, F; Ferrer, A; Almeda, J; San Jose, A; Gil, A; Pujol, R

    2011-02-01

    To calculate the prevalence of hypovitaminosis D in subjects aged 85 years old and to study the relationship between some common geriatric evaluation scales and vitamin D status. Prospective cohort study. A community-based study. 312 subjects aged 85 years old. Geriatric assessment was based on comorbidity, functional status according to the Barthel Index (BI) and Lawton Index (LI), cognitive status measured by the Spanish version of the Mini-Mental State Examination (MEC), nutritional risk according to the Mini Nutritional Assessment (MNA), and gait using the Tinetti Gait Scale. Serum 25(OH)D concentrations were used to assess vitamin D status. Hypovitaminosis D was considered as < 25 ng/ml and deficiency < 11 ng/ml. Mean serum 25(OH)D level was 28 ± 30 ng/ml. The prevalence of hypovitaminosis D was 52.5% (38.1% insufficiency and 14.4% deficiency). Men had higher levels than women (32.2 ± 44 vs. 25.2 ± 25 ng/ml; p=0.04). The bivariate analyses identified an association between MNA scores and hypovitaminosis D, and showed that females ande participants with poor BI, Tinetti and MNA scores were associated with deficiency. Logistic regression analysis confirmed a significant association between poor MNA scores and both hypovitaminosis D (p < 0.04, OR 1.066, 95% CI 1.002-1.135) and vitamin D deficiency (p < 0.0001, OR 1.192, 95% CI 1.099-1.293). More than half the population aged 85 years has a vitamin D deficit and 14.4% show a deficiency. A lower score on the MNA scale is associated with a greater likelihood of having lower vitamin D serum values.

  4. Diagnostic methods for assessing maxillary skeletal and dental transverse deficiencies: A systematic review

    PubMed Central

    Sawchuk, Dena; Currie, Kris; Vich, Manuel Lagravere; Palomo, Juan Martin

    2016-01-01

    Objective To evaluate the accuracy and reliability of the diagnostic tools available for assessing maxillary transverse deficiencies. Methods An electronic search of three databases was performed from their date of establishment to April 2015, with manual searching of reference lists of relevant articles. Articles were considered for inclusion if they reported the accuracy or reliability of a diagnostic method or evaluation technique for maxillary transverse dimensions in mixed or permanent dentitions. Risk of bias was assessed in the included articles, using the Quality Assessment of Diagnostic Accuracy Studies tool-2. Results Nine articles were selected. The studies were heterogeneous, with moderate to low methodological quality, and all had a high risk of bias. Four suggested that the use of arch width prediction indices with dental cast measurements is unreliable for use in diagnosis. Frontal cephalograms derived from cone-beam computed tomography (CBCT) images were reportedly more reliable for assessing intermaxillary transverse discrepancies than posteroanterior cephalograms. Two studies proposed new three-dimensional transverse analyses with CBCT images that were reportedly reliable, but have not been validated for clinical sensitivity or specificity. No studies reported sensitivity, specificity, positive or negative predictive values or likelihood ratios, or ROC curves of the methods for the diagnosis of transverse deficiencies. Conclusions Current evidence does not enable solid conclusions to be drawn, owing to a lack of reliable high quality diagnostic studies evaluating maxillary transverse deficiencies. CBCT images are reportedly more reliable for diagnosis, but further validation is required to confirm CBCT's accuracy and diagnostic superiority. PMID:27668196

  5. Splenic artery pseudoaneurysm due to seatbelt injury in a glucose-6-phosphate dehydrogenase-deficient adult.

    PubMed

    Lau, Yu Zhen; Lau, Yuk Fai; Lai, Kang Yiu; Lau, Chu Pak

    2013-11-01

    A 23-year-old man presented with abdominal pain after suffering blunt trauma caused by a seatbelt injury. His low platelet count of 137 × 10(9)/L was initially attributed to trauma and his underlying hypersplenism due to glucose-6-phosphate dehydrogenase (G6PD) deficiency. Despite conservative management, his platelet count remained persistently reduced even after his haemoglobin and clotting abnormalities were stabilised. After a week, follow-up imaging revealed an incidental finding of a pseudoaneurysm (measuring 9 mm × 8 mm × 10 mm) adjacent to a splenic laceration. The pseudoaneurysm was successfully closed via transcatheter glue embolisation; 20% of the spleen was also embolised. A week later, the platelet count normalised, and the patient was subsequently discharged. This case highlights the pitfalls in the detection of a delayed occurrence of splenic artery pseudoaneurysm after blunt injury via routine delayed phase computed tomography. While splenomegaly in G6PD may be a predisposing factor for injury, a low platelet count should arouse suspicion of internal haemorrhage rather than hypersplenism.

  6. Glucose-6-phosphate dehydrogenase deficiency in Tunisia: molecular data and phenotype-genotype association.

    PubMed

    Laouini, N; Bibi, A; Ammar, H; Kazdaghli, K; Ouali, F; Othmani, R; Amdouni, S; Haloui, S; Sahli, C A; Jouini, L; Hadj Fredj, S; Siala, H; Ben Romdhane, N; Toumi, N E; Fattoum, S; Messsaoud, T

    2013-02-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. In this study, we aimed to perform a molecular investigation of G6PD deficiency in Tunisia and to associate clinical manifestations and the degree of deficiency with the genotype. A total of 161 Tunisian subjects of both sexes were screened by spectrophotometric assay for enzyme activity. Out of these, 54 unrelated subjects were selected for screening of the most frequent mutations in Tunisia by PCR/RFLP, followed by size-based separation of double-stranded fragments under non-denaturing conditions on a denaturing high performance liquid chromatography system. Of the 56 altered chromosomes examined, 75 % had the GdA(-) mutation, 14.28 % showed the GdB(-) mutation and no mutations were identified in 10.72 % of cases. Hemizygous males with GdA(-) mutation were mostly of class III, while those with GdB(-) mutation were mainly of class II. The principal clinical manifestation encountered was favism. Acute hemolytic crises induced by drugs or infections and neonatal jaundice were also noted. Less severe clinical features such as low back pain were present in heterozygous females and in one homozygous female. Asymptomatic individuals were in majority heterozygote females and strangely one hemizygous male. The spectrum of mutations seems to be homogeneous and similar to that of Mediterranean countries; nevertheless 10.72 % of cases remain with undetermined mutation thus suggesting a potential heterogeneity of the deficiency at the molecular level. On the other hand, we note a better association of the molecular defects with the severity of the deficiency than with clinical manifestations.

  7. Acquired hemoglobin variants and exposure to glucose-6-phosphate dehydrogenase deficient red blood cell units during exchange transfusion for sickle cell disease in a patient requiring antigen-matched blood.

    PubMed

    Raciti, Patricia M; Francis, Richard O; Spitalnik, Patrice F; Schwartz, Joseph; Jhang, Jeffrey S

    2013-08-01

    Red blood cell exchange (RBCEx) is frequently used in the management of patients with sickle cell disease (SCD) and acute chest syndrome or stroke, or to maintain target hemoglobin S (HbS) levels. In these settings, RBCEx is a category I or II recommendation according to guidelines on the use of therapeutic apheresis published by the American Society for Apheresis. Matching donor red blood cells (RBCs) to recipient phenotypes (e.g., C, E, K-antigen negative) can decrease the risk of alloimmunization in patients with multi-transfused SCD. However, this may select for donors with a higher prevalence of RBC disorders for which screening is not performed. This report describes a patient with SCD treated with RBCEx using five units negative for C, E, K, Fya, Fyb (prospectively matched), four of which were from donors with hemoglobin variants and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency. Pre-RBCEx HbS quantification by high performance liquid chromatography (HPLC) demonstrated 49.3% HbS and 2.8% hemoglobin C, presumably from transfusion of a hemoglobin C-containing RBC unit during a previous RBCEx. Post-RBCEx HPLC showed the appearance of hemoglobin G-Philadelphia. Two units were G6PD-deficient. The patient did well, but the consequences of transfusing RBC units that are G6PD-deficient and contain hemoglobin variants are unknown. Additional studies are needed to investigate effects on storage, in-vivo RBC recovery and survival, and physiological effects following transfusion of these units. Post-RBCEx HPLC can monitor RBCEx efficiency and detect the presence of abnormal transfused units.

  8. Assessment of Actin FS and Actin FSL sensitivity to specific clotting factor deficiencies.

    PubMed

    Lawrie, A S; Kitchen, S; Purdy, G; Mackie, I J; Preston, F E; Machin, S J

    1998-06-01

    We present a two centre study designed to assess the sensitivity of Actin FS and Actin FSL to deficiencies of factor VIII, IX, XI or XII. The study was undertaken at two centres to avoid bias due to the investigations being undertaken on one analyser. Samples from patients with a factor VIII (n = 36, F VIII = < 1.0-50 iu/dl), factor IX (n = 22, F IX = 2-48 iu/dl), factor XI (n = 23, F XI = 5-50 u/dl) or a factor XII (n = 18, F XII = 1-50 u/dl) deficient state were studied. Activated partial thromboplastin times (APTT) were determined using two batches of Actin FS and of Actin FSL; comparison of APTT results between centres was facilitated by the conversion of clotting times to ratios (test divided by geometric mean normal clotting time). APTT ratios were considered to be elevated if greater than two standard deviations above the mean normal. The factor deficient status of each sample was verified by assaying all samples for factors VIII, IX, XI and XII. Clotting factor assays were performed on a Sysmex CA-1000 fitted with research software, which permitted the auto-dilution and testing of three serial dilution of both a reference preparation and each patient's sample. Assay results were calculated using parallel-line Bioassay principles. This procedure allowed for variation in clotting times due to the effect of temporal drift of any of the reagents within the assay system. Actin FS and Actin FSL demonstrate acceptable sensitivity to factor VIII deficiency, however, both reagents failed to detect a large proportion of factor XI (17.4% and 30.4% of samples, respectively) and factor XII (66.7% and 72.2%, respectively) deficiencies. The detection rate with Actin FSL for factor IX deficiency was also poor (36.4% not detected). As factor IX and XI deficiencies are both associated with haemorrhagic disorders, the inability of these reagents to detect such abnormalities gave cause for concern.

  9. Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors.

    PubMed

    Kiss, Joseph E; Steele, Whitney R; Wright, David J; Mast, Alan E; Carey, Patricia M; Murphy, Edward L; Gottschall, Jerry L; Simon, Toby L; Cable, Ritchard G

    2013-11-01

    Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 μg/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 μg/L was a good surrogate for assessing IDE. RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency. © 2013 American Association of Blood Banks.

  10. Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors

    PubMed Central

    Kiss, Joseph E.; Steele, Whitney R.; Wright, David J.; Mast, Alan E.; Carey, Patricia M.; Murphy, Edward L.; Gottschall, Jerry L.; Simon, Toby L.; Cable, Ritchard G.

    2014-01-01

    BACKGROUND Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. STUDY DESIGN AND METHODS A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/ RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 µ.g/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. RESULTS HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 u.g/L was a good surrogate for assessing IDE. CONCLUSION RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency. PMID:23617531

  11. A statistical assessment of population trends for data deficient Mexican amphibians

    PubMed Central

    Thessen, Anne E.; Arias-Caballero, Paulina; Ayala-Orozco, Bárbara

    2014-01-01

    Background. Mexico has the world’s fifth largest population of amphibians and the second country with the highest quantity of threatened amphibian species. About 10% of Mexican amphibians lack enough data to be assigned to a risk category by the IUCN, so in this paper we want to test a statistical tool that, in the absence of specific demographic data, can assess a species’ risk of extinction, population trend, and to better understand which variables increase their vulnerability. Recent studies have demonstrated that the risk of species decline depends on extrinsic and intrinsic traits, thus including both of them for assessing extinction might render more accurate assessment of threats. Methods. We harvested data from the Encyclopedia of Life (EOL) and the published literature for Mexican amphibians, and used these data to assess the population trend of some of the Mexican species that have been assigned to the Data Deficient category of the IUCN using Random Forests, a Machine Learning method that gives a prediction of complex processes and identifies the most important variables that account for the predictions. Results. Our results show that most of the data deficient Mexican amphibians that we used have decreasing population trends. We found that Random Forests is a solid way to identify species with decreasing population trends when no demographic data is available. Moreover, we point to the most important variables that make species more vulnerable for extinction. This exercise is a very valuable first step in assigning conservation priorities for poorly known species. PMID:25548736

  12. Nutritional assessment methods for zinc supplementation in prepubertal non-zinc-deficient children

    PubMed Central

    Lopes, Márcia Marília Gomes Dantas; de Brito, Naira Josele Neves; de Medeiros Rocha, Érika Dantas; França, Mardone Cavalcante; de Almeida, Maria das Graças; Brandão-Neto, José

    2015-01-01

    Background Zinc is an essential nutrient that is required for numerous metabolic functions, and zinc deficiency results in growth retardation, cell-mediated immune dysfunction, and cognitive impairment. Objective This study evaluated nutritional assessment methods for zinc supplementation in prepubertal non-zinc-deficient children. Design We performed a randomised, controlled, triple-blind study. The children were divided into a control group (10% sorbitol, n=31) and an experimental group (10 mg Zn/day, n=31) for 3 months. Anthropometric and dietary assessments as well as bioelectrical measurements were performed in all children. Results Our study showed (1) an increased body mass index for age and an increased phase angle in the experimental group; (2) a positive correlation between nutritional assessment parameters in both groups; (3) increased soft tissue, and mainly fat-free mass, in the body composition of the experimental group, as determined using bioelectrical impedance vector analysis; (4) increased consumption of all nutrients, including zinc, in the experimental group; and (5) an increased serum zinc concentration in both groups (p<0.0001). Conclusions Given that a reference for body composition analysis does not exist for intervention studies, longitudinal studies are needed to investigate vector migration during zinc supplementation. These results reinforce the importance of employing multiple techniques to assess the nutritional status of populations. PMID:26507491

  13. A statistical assessment of population trends for data deficient Mexican amphibians.

    PubMed

    Quintero, Esther; Thessen, Anne E; Arias-Caballero, Paulina; Ayala-Orozco, Bárbara

    2014-01-01

    Background. Mexico has the world's fifth largest population of amphibians and the second country with the highest quantity of threatened amphibian species. About 10% of Mexican amphibians lack enough data to be assigned to a risk category by the IUCN, so in this paper we want to test a statistical tool that, in the absence of specific demographic data, can assess a species' risk of extinction, population trend, and to better understand which variables increase their vulnerability. Recent studies have demonstrated that the risk of species decline depends on extrinsic and intrinsic traits, thus including both of them for assessing extinction might render more accurate assessment of threats. Methods. We harvested data from the Encyclopedia of Life (EOL) and the published literature for Mexican amphibians, and used these data to assess the population trend of some of the Mexican species that have been assigned to the Data Deficient category of the IUCN using Random Forests, a Machine Learning method that gives a prediction of complex processes and identifies the most important variables that account for the predictions. Results. Our results show that most of the data deficient Mexican amphibians that we used have decreasing population trends. We found that Random Forests is a solid way to identify species with decreasing population trends when no demographic data is available. Moreover, we point to the most important variables that make species more vulnerable for extinction. This exercise is a very valuable first step in assigning conservation priorities for poorly known species.

  14. Therapeutic Assessment of Chloroquine-Primaquine Combined Regimen in Adult Cohort of Plasmodium vivax Malaria from Primary Care Centres in Southwestern India

    PubMed Central

    Saravu, Kavitha; Kumar, Rishikesh; Ashok, Herikudru; Kundapura, Premananda; Kamath, Veena; Kamath, Asha; Mukhopadhyay, Chiranjay

    2016-01-01

    Background Several reports of chloroquine treatment failure and resistance in Plasmodium vivax malaria from Southeast Asian countries have been published. Present study was undertaken to assess the efficacy of chloroquine-primaquine (CQ-PQ) combined regimen for the treatment of P. vivax malaria patients who were catered by the selected primary health centres (PHCs) of Udupi taluk, Udupi district, Karnataka, India. Method Five PHCs were selected within Udupi taluk based on probability proportional to size. In-vivo therapeutic efficacy assessment of CQ (1500 mg over three days) plus PQ (210 mg over 14 days) regimen was carried out in accordance with the World Health Organization’s protocol of 28 days follow-up among microscopically diagnosed monoinfection P. vivax cohort. Results In total, 161 participants were recruited in the study of which, 155 (96.3%) participants completed till day 28 follow-up, fully complied with the treatment regimen and showed adequate clinical and parasitological response. Loss to follow up was noted with 5 (3.1%) participants and non-compliance with treatment regimen occurred with one participant (0.6%). Glucose-6-phosphate dehydrogenase deficiency (G6PDd, <30% of normal mean activity) was noted among 5 (3.1%) participants and one of them did develop PQ induced dark-brown urination which subsided after PQ discontinuation. G6PDd patients were treated with PQ 45 mg/week for eight weeks while PQ was discontinued in one case with G6PD 1.4 U/g Hb due to complaint of reddish-brown coloured urine by 48 hours of PQ initiation. Nested polymerase chain reaction test revealed 45 (28%) cases as mixed (vivax and falciparum) malaria. Conclusions The CQ-PQ combined regimen remains outstandingly effective to treat uncomplicated P. vivax malaria in Udupi taluk and thus it should continue as first line regimen. For all P. vivax cases, G6PD screening before PQ administration must be mandatory and made available in all PHCs. PMID:27315280

  15. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature.

    PubMed

    Pawlak, R; Lester, S E; Babatunde, T

    2014-05-01

    Individuals following vegetarian diets are at risk for developing vitamin B12 deficiency owing to suboptimal intake. As vitamin B12 is essential for the synthesis of nucleic acids, erythrocytes and in the maintenance of myelin, deficiency may result in a variety of symptoms. Some of these symptoms may be severe while others may be irreversible. The objective of this review was to assess vitamin B12 deficiency, based on reported serum vitamin B12, among individuals adhering to different types of vegetarian diets. A systematic literature search was carried out using multiple search engines including PubMed, Medline, CINAHL plus, ERIC, Nursing and Allied Health Collection and Nursing/Academic Edition. The inclusion criteria consisted of original studies that assessed serum vitamin B12, studies written in English, non-case studies and studies that reported actual percentages of vitamin B12 deficiency. Forty research studies were included. The deficiency prevalence among infants reached 45%. The deficiency among the children and adolescents ranged from 0 to 33.3%. Deficiency among pregnant women ranged from 17 to 39%, dependent on the trimester. Adults and elderly individuals had a deficiency range of 0-86.5%. Higher deficiency prevalence was reported in vegans than in other vegetarians. Thus, with few exceptions, the reviewed studies documented relatively high deficiency prevalence among vegetarians. Vegans who do not ingest vitamin B12 supplements were found to be at especially high risk. Vegetarians, especially vegans, should give strong consideration to the use of vitamin B12 supplements to ensure adequate vitamin B12 intake. Vegetarians, regardless of the type of vegetarian diet they adhere to, should be screened for vitamin B12 deficiency.

  16. Assessment of ataxia phenotype in a new mouse model of galactose-1 phosphate uridylyltransferase (GALT) deficiency.

    PubMed

    Chen, Wyman; Caston, Rose; Balakrishnan, Bijina; Siddiqi, Anwer; Parmar, Kamalpreet; Tang, Manshu; Feng, Merry; Lai, Kent

    2017-01-01

    Despite adequate dietary management, patients with classic galactosemia continue to have increased risks of cognitive deficits, speech dyspraxia, primary ovarian insufficiency, and abnormal motor development. A recent evaluation of a new galactose-1 phosphate uridylyltransferase (GALT)-deficient mouse model revealed reduced fertility and growth restriction. These phenotypes resemble those seen in human patients. In this study, we further assess the fidelity of this new mouse model by examining the animals for the manifestation of a common neurological sequela in human patients: cerebellar ataxia. The balance, grip strength, and motor coordination of GALT-deficient and wild-type mice were tested using a modified rotarod. The results were compared to composite phenotype scoring tests, typically used to evaluate neurological and motor impairment. The data demonstrated abnormalities with varying severity in the GALT-deficient mice. Mice of different ages were used to reveal the progressive nature of motor impairment. The varying severity and age-dependent impairments seen in the animal model agree with reports on human patients. Finally, measurements of the cerebellar granular and molecular layers suggested that mutant mice experience cerebellar hypoplasia, which could have resulted from the down-regulation of the PI3K/Akt signaling pathway.

  17. Lack of international uniformity in assessing color vision deficiency in professional pilots.

    PubMed

    Watson, Dougal B

    2014-02-01

    Color is an important characteristic of the aviation environment. Pilots must rapidly and accurately differentiate and identify colors. The medical standards published by the International Civil Aviation Organization (ICAO) require that pilots have "the ability to perceive readily those colors the perception of which is necessary for the safe performance of duties." The general wording of that color vision (CV) standard, coupled with the associated flexibility provisions, allows for different approaches to the assessment of color vision deficient (CVD) pilots. Data was gathered and analyzed regarding medical assessment practices applied by different countries to CVD pilots. Data was obtained from 78 countries, representing 78% of the population and 92% of the aviation activity of the world. That data indicates wide variation in the medical assessment of CVD pilots. Countries use different tools and procedures for the testing of pilots, and also apply different result criteria to those tests. At one extreme an applicant making one error upon Ishihara 24-plate pseudoisochromatic plate (PIP) testing is declined a class 1 medical assessment, while at another extreme an applicant failing every color vision test required by the regulatory authority may be issued a medical assessment allowing commercial and airline copilot privileges. The medical assessment of CVD applicants is not performed consistently across the world. Factors that favor uniformity have been inadequate to encourage countries toward consistent medical assessment outcomes. This data is not consistent with the highest practicable degree of uniformity in medical assessment outcomes, and encourages aeromedical tourism.

  18. [Nutritional assessment of gluten-free diet. Is gluten-free diet deficient in some nutrient?].

    PubMed

    Salazar Quero, J C; Espín Jaime, B; Rodríguez Martínez, A; Argüelles Martín, F; García Jiménez, R; Rubio Murillo, M; Pizarro Martín, A

    2015-07-01

    The gluten-free diet has traditionally been accepted as a healthy diet, but there are articles advocating that it may have some nutritional deficiencies. The current study assesses whether there was any change in the contributions of calories, essential elements, proportion of fatty acids, vitamins, minerals and fiber in children who were diagnosed with celiac diseases, comparing the diet with gluten prior one year after diagnosis with the diet without gluten to the year of diagnosis. The level of clinical or analytical impact that nutritional deficits could have was also assessed. A prospective,descriptive, observational study in which information was collected from a dietary survey, anthropometric and analytical data at pre-diagnosis of celiac disease and following a gluten diet and one year after celiac disease diagnosis, under gluten-free diet. A total of 37 patients meet the study criteria. A decrease in the intake of saturated fatty acids was found, with an increase of monounsaturated fatty acids and an increase in the intake of phosphorus in the diet without gluten. A deficient intake of vitamin D was found in both diets. Clinically, at year of gluten-free diet there was an improvement in weight and size. Analytically, there was an improvement in hemoglobin, ferritin, vitamin D, and parathyroid hormone in plasma. The gluten-free diet has minimal deficiencies, similar to those present in the diet with gluten, with an improvement in the lipid profile by increasing the proportion of monounsaturated fatty acids to the detriment of saturated fatty acids. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  19. Choosing a Drug to Prevent Malaria

    MedlinePlus

    ... used in patients with glucose-6-phosphatase dehydrogenase (G6PD) deficiency Cannot be used in patients who have not been tested for G6PD deficiency There are costs and delays associated with getting ...

  20. Pegloticase Injection

    MedlinePlus

    ... doctor if you have glucose-6-phosphate dehydrogenase (G6PD) deficiency (an inherited blood disease). Your doctor may test you for G6PD deficiency before you start to receive pegloticase injection. If ...

  1. Apert syndrome with glucose-6-phosphate dehydrogenase deficiency: a case report.

    PubMed

    Tosun, G; Sener, Y

    2006-05-01

    Apert syndrome is characterized by midface hypoplasia, syndactyly of the hands and feet, proptosis of eyes, steep and flat frontal bones, and premature union of cranial sutures. Maxillary hypoplasia, deep palatal vault, anterior open bite, crowding of the dental arch, severely delayed tooth eruption, and dental malocclusion are the main oral manifestations of this syndrome. In this report, a case of Apert syndrome with glucose-6-phosphate dehydrogenase (G(6)PD) deficiency is presented. The patient, a 4-year-old male and the fourth child of healthy parents, was admitted to our department because of delayed tooth eruption. He had all the cardinal symptoms of the Apert syndrome. Clinical examination revealed that primary centrals, canines and first molars erupted; however, primary second molars and laterals had not erupted. The patient had no dental caries. Preventive treatments were applied, and subsequently, the patient was taken to long-term follow up.

  2. Defining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency.

    PubMed

    Wong, Sunnie Yan-Wai; Beamer, Lesa J; Gadomski, Therese; Honzik, Tomas; Mohamed, Miski; Wortmann, Saskia B; Brocke Holmefjord, Katja S; Mork, Marit; Bowling, Francis; Sykut-Cegielska, Jolanta; Koch, Dieter; Ackermann, Amanda; Stanley, Charles A; Rymen, Daisy; Zeharia, Avraham; Al-Sayed, Moeen; Marquardt, Thomas; Jaeken, Jaak; Lefeber, Dirk; Conrad, Donald F; Kozicz, Tamas; Morava, Eva

    2016-08-01

    To define phenotypic groups and identify predictors of disease severity in patients with phosphoglucomutase-1 deficiency (PGM1-CDG). We evaluated 27 patients with PGM1-CDG who were divided into 3 phenotypic groups, and group assignment was validated by a scoring system, the Tulane PGM1-CDG Rating Scale (TPCRS). This scale evaluates measurable clinical features of PGM1-CDG. We examined the relationship between genotype, enzyme activity, and TPCRS score by using regression analysis. Associations between the most common clinical features and disease severity were evaluated by principal component analysis. We found a statistically significant stratification of the TPCRS scores among the phenotypic groups (P < .001). Regression analysis showed that there is no significant correlation between genotype, enzyme activity, and TPCRS score. Principal component analysis identified 5 variables that contributed to 54% variance in the cohort and are predictive of disease severity: congenital malformation, cardiac involvement, endocrine deficiency, myopathy, and growth. We established a scoring algorithm to reliably evaluate disease severity in patients with PGM1-CDG on the basis of their clinical history and presentation. We also identified 5 clinical features that are predictors of disease severity; 2 of these features can be evaluated by physical examination, without the need for specific diagnostic testing and thus allow for rapid assessment and initiation of therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Assessment of iodine deficiency in school age children in Nainital District, Uttarakhand State.

    PubMed

    Kapil, Umesh; Pandey, Ravindra Mohan; Prakash, Shyam; Kabra, Madhulika; Sareen, Neha; Bhadoria, Ajeet Singh

    2014-01-01

    Iodine deficiency disorder (IDD) is a major public health problem in Uttarakhand. The present study was conducted in district Nainital, Uttarakhand state with an objective to assess the prevalence of IDD in school age children. A total of 2269 children in the age group of 6-12 years were included. Clinical examination of thyroid of all children was undertaken. "On the spot" urine samples were collected from 611 children. Salt samples were collected from the family kitchen for 642 children. The Total Goitre Rate (TGR) was 15.9%. The proportion of children with urinary iodine excretion levels <20, 20-49, 50-99, 100-199 and 200 μg/L and above, was nil, 11.8, 24.9, 38.3 and 25.0 percent, respectively. The median Urinary Iodine Excretion level was 125μg/L. About 57.7% of the children were consuming salt with iodine content of 15 ppm and more. Findings of the present study indicates that the population is possibly in transition phase from iodine deficient as revealed by Total Goitre Rate of 15.9% to iodine sufficient as revealed by median urinary iodine excretion level of 125 μg/L. There is a need to further strengthen the existing monitoring system for the quality of iodized salt in the district in order to achieve the elimination of IDD.

  4. Assessment of the 21-hydroxylase deficiency and the adrenal functions in young females with Turner syndrome.

    PubMed

    Onder, Asan; Aycan, Zehra; Cetinkaya, Semra; Kendirci, Havva Nur Peltek; Bas, Veysel Nijat; Agladioglu, Sebahat Yilmaz

    2012-01-01

    There are few reports of an association between Turner syndrome (TS) and 21-hydroxylase deficiency. However, this association is more frequent in some populations. The aim of this study was to evaluate the incidence of 21-hydroxylase deficiency in patients with TS in our population. 21-hydroxylase deficiency was evaluated in 44 TS cases with 45X (n=20) and 24 mosaic cases. A standard dose adrenocorticotropic (ACTH) stimulation test (Synacthen, Novartis, Basel, Switzerland) was performed, and 17 hydroxyprogesterone (17OHP), dehydroepiandrosterone sulfate (DHEAS) and cortisol responses were evaluated. Patients with increased 17OHP responses in the stimulation test also underwent 21-hydroxylase gene analysis. The mean age was 14.6 +/- 4 (2.6-22.4); 37 patients were on growth hormone (GH) treatment. Nine patients were at prepubertal stage, whereas 35 were pubertal (24 on gonadal steroids and 11 spontaneously). Six patients were obese. Only one of our patients had a level of 7.5 ng/mL of 17OHP, and there was no mutation found in congenital adrenal hyperplasia (CAH) genetic analysis. In other cases, peak 17OHP levels were < or = 6 ng/mL. The mean peak 17OHP was 2.62 +/- 1.48 (1.19-7.5) ng/mL, the cortisol level was 37.6 +/- 8.43 (23.9-56.2) microg/dL and the DHEAS was 135.2+/- 87.3 (15-413) microg/dL. The increased mean basal and peak cortisol levels (20.5 +/- 10.2 and 37.6 +/- 8.4 microg/dL) were remarkable findings. Whereas basal cortisol was above 20 microg/dL in 38.7% of patients, exaggerated results up to 56.2 microg/dL were obtained in peak cortisol levels. The basal and peak 17OHP cortisol levels were not correlated with the presence of puberty, chromosome structure, gonadal steroid use, obesity or growth hormone use. This trial suggested that 21-hydroxylase deficiency was not common among patients with TS in our population. Adrenal function should be assessed, at least in the presence of clitoral enlargement in patients with TS, particularly if their karyotype

  5. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali.

    PubMed

    Maiga, Bakary; Dolo, Amagana; Campino, Susana; Sepulveda, Nuno; Corran, Patrick; Rockett, Kirk A; Troye-Blomberg, Marita; Doumbo, Ogobara K; Clark, Taane G

    2014-07-11

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (<1% versus Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in

  6. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali

    PubMed Central

    2014-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. Methods A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. Results It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (< 1% versus Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was

  7. Single Cell Cytochemistry Illustrated by the Demonstration of Glucose-6-Phosphate Dehydrogenase Deficiency in Erythrocytes.

    PubMed

    Peters, Anna L; van Noorden, Cornelis J F

    2017-01-01

    Cytochemistry is the discipline that is applied to visualize specific molecules in individual cells and has become an essential tool in life sciences. Immunocytochemistry was developed in the sixties of last century and is the most frequently used cytochemical application. However, metabolic mapping is the oldest cytochemical approach to localize activity of specific enzymes, but in the last decades of the previous century and the first decade of the present century it almost became obsolete. The popularity of this approach revived in the past few years. Metabolism gained interest as player in chronic and complex diseases such as cancer, diabetes, neurodegenerative diseases, and vascular diseases and both enzyme cytochemistry and metabolic mapping have become important tools in life sciences.In this chapter, we present glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most prevalent enzyme deficiency worldwide, to illustrate recent developments in enzyme cytochemistry or metabolic mapping. The first assays which were developed quantified enzyme activity but were unreliable for single cell evaluation. The field has expanded with the development of cytochemical single cell assays and DNA testing. Still, all assays-from the earliest developed tests up to the most recently developed tests-have their place in investigations on G6PD activity. Recently, nanoscopy has become available for light and fluorescence microscopy at the nanoscale. For nanoscopy, cytochemistry is an essential tool to visualize intracellular molecular processes. The ultimate goal in the coming years will be nanoscopy of living cells so that the molecular dynamics can be studied. Cytochemistry will undoubtedly play a critical role in these developments.

  8. Critical Deficiency Ratings in Milestone Assessment: A Review and Case Study.

    PubMed

    Kinnear, Benjamin; Bensman, Rachel; Held, Justin; O'Toole, Jennifer; Schauer, Daniel; Warm, Eric

    2017-06-01

    The Accreditation Council for Graduate Medical Education (ACGME) requires programs to report learner progress using specialty-specific milestones. It is unclear how milestones can best identify critical deficiencies (CDs) in trainee performance. Specialties developed milestones independently of one another; not every specialty included CDs within milestones ratings. This study examined the proportion of ACGME milestone sets that include CD ratings, and describes one residency program's experiences using CD ratings in assessment. The authors reviewed ACGME milestones for all 99 specialties in November 2015, determining which rating scales contained CDs. The authors also reviewed three years of data (July 2012-June 2015) from the University of Cincinnati Medical Center (UCMC) internal medicine residency assessment system based on observable practice activities mapped to ACGME milestones. Data were analyzed by postgraduate year, assessor type, rotation, academic year, and core competency. The Mantel-Haenszel chi-square test was used to test for changes over time. Specialties demonstrated heterogeneity in accounting for CDs in ACGME milestones, with 22% (22/99) of specialties having no language describing CDs in milestones assessment. Thirty-three percent (63/189) of UCMC internal medicine residents received at least one CD rating, with CDs accounting for 0.18% (668/364,728) of all assessment ratings. The authors identified CDs across multiple core competencies and rotations. Despite some specialties not accounting for CDs in milestone assessment, UCMC's experience demonstrates that a significant proportion of residents may be rated as having a CD during training. Identification of CDs may allow programs to develop remediation and improvement plans.

  9. Assessment of anterolateral rotatory instability in the anterior cruciate ligament-deficient knee using an open magnetic resonance imaging system.

    PubMed

    Okazaki, Ken; Miura, Hiromasa; Matsuda, Shuich; Yasunaga, Takefumi; Nakashima, Hideaki; Konishi, Kozo; Iwamoto, Yukihide; Hashizume, Makoto

    2007-07-01

    In the clinical evaluation of the anterior cruciate ligament-deficient knee, anterolateral rotatory instability is assessed by manual tests such as the pivot-shift test, which is subjective and not quantitative. The anterolateral rotatory instability in an anterior cruciate ligament-deficient knee can be quantified by our newly developed method using open magnetic resonance imaging. Controlled laboratory study. Eighteen subjects with anterior cruciate ligament-deficient knees and 18 with normal knees were recruited. We administered the Slocum anterolateral rotatory instability test in the open magnetic resonance imaging scanner and scanned the sagittal view of the knee. The anterior displacements of the tibia at the medial and lateral compartments were measured. Furthermore, we examined 14 anterior cruciate ligament-deficient knees twice to assess intraobserver and interobserver reproducibility and evaluated the difference and interclass correlation coefficient of 2 measures. In the anterior cruciate ligament-deficient knee, displacement was 14.4 +/- 5.5 mm at the lateral compartment and 1.6 +/- 2.3 mm at the medial compartment; in the normal knee, displacement was 0.7 +/- 1.9 mm and -1.1 +/- 1.2 mm, respectively. The difference and interclass correlation coefficient between 2 repeated measures at the lateral compartment were 1.0 +/- 0.7 mm and .98 for intraobserver reproducibility and 1.1 +/- 0.7 mm and .91 for interobserver reproducibility. This method is useful to assess the anterolateral rotatory instability of the anterior cruciate ligament-deficient knee. This method can be used in the clinical assessment of anterior cruciate ligament stability, such as comparing studies of graft positions or 2-bundle anatomic reconstruction and the conventional 1-bundle technique.

  10. Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD

    SciTech Connect

    Gregor, P.; Nash, S.R.; Caron, M.G.

    1995-01-01

    The creatine-phosphocreatine shuttle has important functions in the temporal and spatial maintenance of the energy supply to skeletal and cardiac muscle. Muscle cells do not synthesize creatine, but take it up via a specific sodium-dependent transporter - the creatine transporter. Thus, the creatine transporter has an important role in muscular physiology. Furthermore, inhibition of creatine transport in experimental animals causes muscle weakness. Recently, creatine transporter cDNAs have been isolated and characterized from rabbit and human. In this communication we report mapping of the creatine transporter gene to human chromosome Xq28. 12 refs., 1 fig.

  11. 26 CFR 1.1311(b)-3 - Existence of relationship in case of adjustment by way of deficiency assessment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Existence of relationship in case of adjustment by way of deficiency assessment. 1.1311(b)-3 Section 1.1311(b)-3 Internal Revenue INTERNAL REVENUE...) Readjustment of Tax Between Years and Special Limitations § 1.1311(b)-3 Existence of relationship in case of...

  12. 26 CFR 1.1311(b)-3 - Existence of relationship in case of adjustment by way of deficiency assessment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Existence of relationship in case of adjustment by way of deficiency assessment. 1.1311(b)-3 Section 1.1311(b)-3 Internal Revenue INTERNAL REVENUE... Between Years and Special Limitations § 1.1311(b)-3 Existence of relationship in case of adjustment by way...

  13. 26 CFR 1.1311(b)-3 - Existence of relationship in case of adjustment by way of deficiency assessment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 11 2012-04-01 2012-04-01 false Existence of relationship in case of adjustment by way of deficiency assessment. 1.1311(b)-3 Section 1.1311(b)-3 Internal Revenue INTERNAL REVENUE...) Readjustment of Tax Between Years and Special Limitations § 1.1311(b)-3 Existence of relationship in case of...

  14. 26 CFR 1.1311(b)-3 - Existence of relationship in case of adjustment by way of deficiency assessment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 11 2013-04-01 2013-04-01 false Existence of relationship in case of adjustment by way of deficiency assessment. 1.1311(b)-3 Section 1.1311(b)-3 Internal Revenue INTERNAL REVENUE...) Readjustment of Tax Between Years and Special Limitations § 1.1311(b)-3 Existence of relationship in case of...

  15. Acute viral hepatitis, intravascular haemolysis, severe hyperbilirubinaemia and renal failure in glucose-6-phosphate dehydrogenase deficient patients.

    PubMed Central

    Agarwal, R. K.; Moudgil, A.; Kishore, K.; Srivastava, R. N.; Tandon, R. K.

    1985-01-01

    Five patients with acute viral hepatitis developed severe intrasvascular haemolysis and unusually high levels of serum bilirubin (427 to 1368 mumol/l). All 5 had high fever, marked anaemia, reticulocytosis and neutrophilic leucocytosis. Three of them developed acute renal failure, which was of non-oliguric type in 2. The clinical course was protracted, but complete recovery occurred in 4 patients between 4 to 10 weeks. One patient with hepatic coma and oliguric renal failure died. Deficiency of the enzyme G-6-PD was confirmed in 4 cases. Massive haemolysis in the patients was probably induced by the administration of chloroquine and other drugs. Intravascular haemolysis should be suspected in patients with acute viral hepatitis, if they show unexplained anaemia and very high serum bilirubin levels, and measures to prevent renal failure should be instituted in such cases. PMID:4070114

  16. Co-occurrence of biphenotypic acute leukaemia, glucose 6-phosphate dehydrogenase deficiency and haemoglobin E trait in a single child.

    PubMed

    Mallick, Debkrishna; Thapa, Rajoo; Biswas, Biswajit

    2016-02-01

    Acute leukaemias occur as the result of clonal expansion subsequent to transformation and arrest at a normal differentiation stage of haematopoietic precursors, which commit to a single lineage, such as myeloid or B-lymphoid or T-lymphoid cells. Biphenotypic acute leukaemia (BAL) constitutes a biologically different group of leukaemia arising from a precursor stem cell and co-expressing more than one lineage specific marker. The present report describes a child with unusual co-occurrence of biphenotypic (B-precursor cell and Myeloid) acute leukaemia, haemoglobin E trait and glucose 6-phosphate dehydrogenase (G6-PD) deficiency. To the best of our knowledge, this constellation of haematological conditions in a single child has never been described before.

  17. Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

    PubMed Central

    Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

    2012-01-01

    Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

  18. Genetics Home Reference: glucose-6-phosphate dehydrogenase deficiency

    MedlinePlus

    ... as some antibiotics and medications used to treat malaria). Hemolytic anemia can also occur after eating fava ... a G6PD mutation may be partially protected against malaria, an infectious disease carried by a certain type ...

  19. Use of combined measures from capillary blood to assess iron deficiency in rural Kenyan children.

    PubMed

    Shell-Duncan, Bettina; McDade, Thomas

    2004-02-01

    Community-based surveys of iron deficiency (ID) require simple, accurate methods that can be used in remote areas. The objective of this study was to assess iron status in rural Kenya using "field-friendly" methods for capillary blood, including an improved dried blood spot assay for transferrin receptor (TfR). A single finger stick was used to obtain capillary blood from 275 school-age children. Whole blood was applied directly to filter paper, dried, and later analyzed for TfR, as well as C-reactive protein (CRP), an acute-phase protein that serves as a general marker of inflammation. Capillary blood was also used to measure hemoglobin (Hb) concentration and the ratio of zinc protoporphyrin to heme (ZPP:H). The Hb concentration alone provides the lowest estimate of the prevalence of ID (8.0%). Because ZPP:H is reported to be elevated in the presence of inflammation, we constructed a preliminary diagnostic model based on elevated ZPP:H and normal CRP level, estimating the prevalence of ID at 25.9%. When TfR is added to a multiple criteria model (elevated ZPP:H in the absence of elevated CRP and/or elevated TfR level) the prevalence of ID is estimated to be 31.2%. This study demonstrates the diagnostic utility of combining TfR with other indexes of iron status, enabling the detection of ID in both the presence and absence of infection. Furthermore, this study is the first field application of TfR blood-spot methods, and it demonstrates their feasibility in remote field settings.

  20. [A FOOD FREQUENCY QUESTIONNAIRE TO ASSESS DIET QUALITY IN THE PREVENTION OF IRON DEFICIENCY].

    PubMed

    Toxqui Abascal, Laura; Díaz Álvarez, Alejandra; Vaquero, María Pilar

    2015-09-01

    Despite the extensive knowledge on iron bioavailability, a Food Frequency Questionnaire (FFQ) for application in population groups predisposed to iron deficiency anaemia has not been implemented. To design a FFQ based on enhancers and inhibitors of iron absorption and to assess its applicability in a group of women at childbearing age. the FFQ included 28 items and the time of consumption for 10 of them, breakfast (B) and lunch/dinner(LD). One hundred and seventy nine healthy young women were selected and distributed into three groups according to their iron status measured by serum ferritin:< 15, 15-30 or > 30 ng/mL. the reproducibility of this FFQ was very high(Spearman coefficient > 0.500, p < 0.001 for all variables). Red meat and alcoholic beverages consumption was positively associated with ferritin, while citric fruits-LD and nuts-LD were negatively associated (p < 0.05). Citric fruits-LD was negatively associated with red meat (p < 0.05) and positively with legumes, fish, salad, vegetables,foods fortified with fiber, other fruits (p < 0.001)and brown bread (p < 0.05). The consumption of fruit juices with breakfast was lower in women with ferritin <15 ng/ml compared to ferritin 15-30 ng/ml. this questionnaire is simple and reproducible.Red meat is the main dietary factor related with higher iron status in young women, thus its influence on iron absorption compared to other enhancers and inhibitors is highlighted. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  1. Risk assessment of obstructive sleep apnea syndrome in pediatric patients with vitamin D deficiency

    PubMed Central

    Ozgurhan, Gamze; Vehapoglu, Aysel; Vermezoglu, Oznur; Temiz, Rabia Nur; Guney, Asuman; Hacihamdioglu, Bulent

    2016-01-01

    Abstract The aim of the following study is to evaluate the risk of obstructive sleep apnea syndrome (OSAS) in subjects with vitamin D deficiency. Prospective and comparative study. We enrolled 240 subjects into the study. The participants were divided into 2 groups based on 25-hydroxyvitamin D (25[OH]D) levels: low level of 25(OH)D (<20 ng/mL) group (n = 120) and control (>20 ng/mL) group (n = 120). Subjects were classified as being at a high or low risk of developing OSAS by using the Berlin Questionnaire. Risk of developing OSAS, gender, age, and body mass index (BMI) z-score were assessed by comparing the low level of 25(OH)D group and control group. No statistically significant difference was observed between the low level of 25(OH)D group and control group in terms of gender, age, and BMI z-score distributions; P = 0.323, P = 0.387, and P = 0.093, respectively. There were 24 subjects with high risk of developing OSAS in 2 groups (17 subjects in the low level of 25[OH]D group and 7 subjects in the control group). In the low level of 25(OH)D group, the risk of developing OSAS was found to be significantly higher than the control group (P = 0.030). BMI z-score was found significantly higher in high-risk groups than low-risk groups (P = 0.034 for low-level 25[OH]D group and P = 0.023 for control group). The findings revealed that low level of 25(OH)D increases the risk of developing OSAS. PMID:27684795

  2. Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency.

    PubMed

    Ardabili, Hania R; Gargari, Bahram P; Farzadi, Laya

    2012-03-01

    Insulin resistance is one of the most common features of polycystic ovary syndrome (PCOS). Some studies suggest that vitamin D deficiency may have a role in insulin resistance; thus, the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency. We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency. The current study was a randomized, placebo-controlled, double-blinded trial with 50 women with PCOS and a vitamin D deficiency, 20 to 40 years old, assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D₃ or a placebo (1 every 20 days) for 2 months (vitamin D, n = 24; placebo, n = 26). The fasting blood glucose, insulin, 25-hydroxyvitamin D, and parathyroid hormone levels, as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment. In the vitamin D group, the serum level of 25-hydroxyvitamin D increased (6.9 ± 2.8 to 23.4 ± 6.1 ng/mL, P < .0001), and the parathyroid hormone level decreased (70.02 ± 43.04 to 50.33 ± 21.99 μ IU/mL, P = .02). There were no significant changes in the placebo group. There was a significant increase in insulin secretion in the vitamin D group (P = .01), but this was not significant compared with the placebo group. The fasting serum insulin and glucose levels and the insulin sensitivity and homeostasis model assessment of insulin resistance did not change significantly by the end of the study. We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency.

  3. Assessment of selenium bioavailability from naturally produced high-selenium soy foods in selenium-deficient rats

    USDA-ARS?s Scientific Manuscript database

    We assessed the bioavailability of selenium (Se) from protein isolate and tofu (bean curd) prepared from naturally produced high-Se soybeans in a Se-deficient rat model. The Se content of soybean seeds, protein isolate and tofu was 5.17 ± 0.22, 11.44 ± 0.09 and 7.37 ± 0.12 mg/kg, respectively. Male ...

  4. Assessment of brain cognitive functions in patients with vitamin B12 deficiency using resting state functional MRI: A longitudinal study.

    PubMed

    Gupta, Lalit; Gupta, Rakesh Kumar; Gupta, Pradeep K; Malhotra, Hardeep Singh; Saha, Indrajit; Garg, Ravindra K

    2016-02-01

    The resting state functional MRI (rsfMRI) approach is useful to explore the brain's functional organization in health and disease conditions. In this study, using rsfMRI the alteration in brain due to vitamin B12 deficiency and reversibility of these alterations following therapy was studied. Thirteen patients with clinical and biochemical evidence of vitamin B12 deficiency were recruited in this study. Fifteen age and sex matched healthy controls were also included. Patients and controls were clinically evaluated using neuropsychological test (NPT). The analysis was carried out using regional homogeneity (ReHo) and low frequency oscillations (LFO) of BOLD signals in resting state. Six patients were also evaluated with rsfMRI and NPT after 6 weeks replacement therapy. ReHo values in patients with vitamin B12 deficiency were significantly lower than controls in the entire cerebrum and the brain networks associated with cognition control, i.e., default mode, cingulo-opercular and fronto-parietal network. There was no significant difference using LFO and it did not show significant correlations with NPT scores. ReHo showed significant correlation with NPT scores. All the 6 patients showed increase in ReHo after replacement therapy. We conclude that brain networks associated with cognition control are altered in patients with vitamin B12 deficiency, which partially recover following six weeks of replacement therapy. This is the first study to evaluate the rsfMRI in the light of clinical neuropsychological evaluation in patients. rsfMRI may be used as functional biomarker to assess therapeutic response in vitamin B12 deficiency patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Physicians' Assessment of Deficiencies and Desire for Training in Adolescent Care.

    ERIC Educational Resources Information Center

    Blum, Robert

    1987-01-01

    In a survey, 351 internists, family practitioners, and pediatricians rated their own competency in 19 areas of adolescent health care. Most felt deficient in all areas, with some variation by physician specialty, but most did not find this an undesirable age group to work with and few wanted to improve their skills. (MSE)

  6. Reticulocyte hemoglobin equivalent (Ret He) and assessment of iron-deficient states

    PubMed Central

    BRUGNARA, C; SCHILLER, B; MORAN, J

    2006-01-01

    Direct measurement of the reticulocyte hemoglobin content provides useful information for the diagnosis and treatment of iron-deficient states. We have examined direct measurements of reticulocyte and red cell hemoglobin content on the Sysmex XE 2100 (Ret He and RBC He respectively) and the Bayer ADVIA 2120 (CHr and CH respectively) analyzers. Good agreement was found between Ret He and CHr (Y = 1.04X − 1.06; r2 = 0.88) and between the RBC He and CH parameters (Y = 0.93X + 1; r2 = 0.84 n = 200) in pediatric patients and in normal adults (Ret He and CHr; Y = 1.06X − 0.43; r2 = 0.83; n = 126; RBC He and CH; Y = 0.94X + 1; r2 = 0.87; n = 126). In 1500 blood samples from patients on chronic dialysis, Ret He was compared with traditional parameters for iron deficiency (serum iron <40 μg/dl, Tsat <20%, ferritin <100 ng/ml, hemoglobin <11 g/dl) for identifying iron-deficient states. Receiver operator characteristic (ROC) curve analysis revealed values of the area under the curve for Ret He of 0.913 (P < 0.0001). With a Ret He cutoff level of 27.2 pg, iron deficiency could be diagnosed with a sensitivity of 93.3%, and a specificity of 83.2%. Ret He is a reliable marker of cellular hemoglobin content and can be used to identify the presence of iron-deficient states. PMID:16999719

  7. Molecular analysis of glucose-6-phosphate dehydrogenase variants in the Solomon Islands

    SciTech Connect

    Hirono, A.; Ishii, A.; Hirono, K.; Miwa, S.; Kere, N.; Fujii, H.

    1995-05-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most prevalent genetic disorders, and >100 million people are considered to have mutant genes. G6PD deficiency is frequent in the area where plasmodium falciparum infection is endemic, probably because the G6PD-deficient subjects are resistant to the parasite. Falciparum and vivax malarias have been highly endemic in the Solomon Islands, and a high frequency of G6PD deficiency has also been expected. A recent investigation showed that the frequency of G6PD deficiency in the Solomon Islands was 8.4%-14.4%. Although >80 G6PD variants from various populations have been molecularly analyzed, little is known about those in Melanesians. G6PD Maewo, which was originally found in Vanuatu, has so far been the only Melanesian variant whose structural abnormality was determined. 14 refs., 1 fig.

  8. Excellent agreement between genetic and hydrogen breath tests for lactase deficiency and the role of extended symptom assessment.

    PubMed

    Pohl, D; Savarino, E; Hersberger, M; Behlis, Z; Stutz, B; Goetze, O; Eckardstein, A V; Fried, M; Tutuian, R

    2010-09-01

    Clinical manifestations of lactase (LCT) deficiency include intestinal and extra-intestinal symptoms. Lactose hydrogen breath test (H2-BT) is considered the gold standard to evaluate LCT deficiency (LD). Recently, the single-nucleotide polymorphism C/T(-13910) has been associated with LD. The objectives of the present study were to evaluate the agreement between genetic testing of LCT C/T(-13910) and lactose H2-BT, and the diagnostic value of extended symptom assessment. Of the 201 patients included in the study, 194 (139 females; mean age 38, range 17-79 years, and 55 males, mean age 38, range 18-68 years) patients with clinical suspicion of LD underwent a 3-4 h H2-BT and genetic testing for LCT C/T(-13910). Patients rated five intestinal and four extra-intestinal symptoms during the H2-BT and then at home for the following 48 h. Declaring H2-BT as the gold standard, the CC(-13910) genotype had a sensitivity of 97% and a specificity of 95% with a κ of 0.9 in diagnosing LCT deficiency. Patients with LD had more intense intestinal symptoms 4 h following the lactose challenge included in the H2-BT. We found no difference in the intensity of extra-intestinal symptoms between patients with and without LD. Symptom assessment yielded differences for intestinal symptoms abdominal pain, bloating, borborygmi and diarrhoea between 120 min and 4 h after oral lactose challenge. Extra-intestinal symptoms (dizziness, headache and myalgia) and extension of symptom assessment up to 48 h did not consistently show different results. In conclusion, genetic testing has an excellent agreement with the standard lactose H2-BT, and it may replace breath testing for the diagnosis of LD. Extended symptom scores and assessment of extra-intestinal symptoms have limited diagnostic value in the evaluation of LD.

  9. Regulation of endocrine-disrupting chemicals: critical overview and deficiencies in toxicology and risk assessment for human health.

    PubMed

    Harvey, Philip W; Everett, David J

    2006-03-01

    Regulation of endocrine-disrupting chemicals is reviewed in terms of hazard assessment (regulatory toxicology) and risk assessment. The current range of regulatory general toxicology protocols can detect endocrine toxicity, but specific endocrine toxicology tests are required to confirm mechanisms (e.g. oestrogenic, anti-androgenic). Strategies for validating new endocrine toxicology protocols and approaches to data assessment are discussed, and deficiencies in regulatory toxicology testing (e.g. lack of adrenocortical function assessment) identified. Recent evidence of a role of prolactin in human breast cancer also highlights deficiencies in regulatory evaluation. Actual human exposure to chemicals and the high-exposure example of chemicals in body-care cosmetics is reviewed with reference to evidence that common ingredients (e.g. parabens, cyclosiloxanes) are oestrogenic. The hypothesis and epidemiology concerning chemical exposure from body-care cosmetics (moisturizers, lotions, sun screens, deodorants) and breast cancer in women is reviewed, applying Bradford-Hill criteria for association and causality, and research requirements are identified.

  10. The impact of thrombin generation and rotation thromboelastometry on assessment of severity of factor XI deficiency.

    PubMed

    Livnat, Tami; Shenkman, Boris; Martinowitz, Uri; Zivelin, Ariella; Dardik, Rima; Tamarin, Ilia; Mansharov, Rachel; Budnik, Ivan; Salomon, Ophira

    2015-08-01

    The phenotype of bleeding in patients with severe FXI deficiency is unpredictable and unlike other bleeding disorders, it is not directly correlated with levels of FXI. In this study we analyzed whether the global coagulation assays can serve as a clinical tool in predicting bleeding tendency in patients with severe FXI deficiency undergoing surgery, taking into account the large inter-individual variability of FXI levels and genotypes. Thrombin generation (TG) was measured in 39 platelet-poor plasma with or without tissue factor (TF) and in the presence or absence of corn trypsin inhibitor (CTI). Rotation thromboelastometry (ROTEM) was performed with fresh whole blood of 26 patients applying NATEM and INTEM tests. TG induced by recalcification can distinguish between bleeding and non-bleeding patients with severe FXI deficiency particularly among those with FXI activity of 2-20IU/dl. The addition of TF or TF and CTI to the TG assay masked the ability to differentiate between XI activity, genotype as well as bleeding and non-bleeding patients. ROTEM assays failed to distinguish bleeding from non-bleeding patients but could do so between different FXI activity levels and genotypes. In conclusion, in the current study we found a sensitive tool to distinguish between bleeding and non-bleeding patients. In order to recommend TG as a predictive tool for treatment tailoring, a larger patient group is required.

  11. Assessing the impact of growth hormone deficiency and treatment in adults: development of a new disease-specific measure.

    PubMed

    Brod, Meryl; Højbjerre, Lise; Adalsteinsson, Johan Erpur; Rasmussen, Michael Højby

    2014-04-01

    Approximately 50 000 adults in the United States are diagnosed with GH deficiency, which has negative impacts on cognitive functioning, psychological well-being, and quality of life. This paper presents development and validation of a patient-reported outcome measure (PRO), the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD). The TRIM-AGHD was developed to measure the impact of GH deficiency and its treatment. The development and validation of the TRIM-AGHD was conducted according to the Food and Drug Administration guidance on the development of PROs. Concept elicitation, conducted in three countries included interviews with patients, clinical experts, and literature review. Qualitative data were analyzed based on grounded theory principles, and draft items were cognitively debriefed. The measure underwent psychometric validation in a US clinic-based population. An a priori statistical analysis plan included assessment of the measurement model, reliability, and validity. Item functioning was reviewed using item response theory analyses. Forty-eight patients and six clinical experts participated in concept elicitation and 169 patients completed the validation study. TRIM-AGHD was measured. Factor analysis resulted in four domains: energy level, physical health, emotional health, and cognitive ability. The item response theory confirmed adequate item fit and placement within their domain. Internal consistency ranged from 0.82 to 0.95 and test-retest ranged from 0.80 to 0.92. All prespecified hypotheses for convergent validity and all but two for discriminant validity were met. The final 26-item TRIM-AGHD can be considered a reliable and valid PRO of the impact of disease and treatment for adult GH deficiency.

  12. A selenium-deficient Caco-2 cell model for assessing differential incorporation of chemical or food selenium into glutathione peroxidase.

    PubMed

    Zeng, Huawei; Botnen, James H; Johnson, Luann K

    2008-01-01

    Assessing the ability of a selenium (Se) sample to induce cellular glutathione peroxidase (GPx) activity in Se-deficient animals is the most commonly used method to determine Se bioavailability. Our goal is to establish a Se-deficient cell culture model with differential incorporation of Se chemical forms into GPx, which may complement the in vivo studies. In the present study, we developed a Se-deficient Caco-2 cell model with a serum gradual reduction method. It is well recognized that selenomethionine (SeMet) is the major nutritional source of Se; therefore, SeMet, selenite, or methylselenocysteine (SeMSC) was added to cell culture media with different concentrations and treatment time points. We found that selenite and SeMSC induced GPx more rapidly than SeMet. However, SeMet was better retained as it is incorporated into proteins in place of methionine; compared with 8-, 24-, or 48-h treatment, 72-h Se treatment was a more sensitive time point to measure the potential of GPx induction in all tested concentrations. Based on induction of GPx activity, the cellular bioavailability of Se from an extract of selenobroccoli after a simulated gastrointestinal digestion was comparable with that of SeMSC and SeMet. These in vitro data are, for the first time, consistent with previous published data regarding selenite and SeMet bioavailability in animal models and Se chemical speciation studies with broccoli. Thus, Se-deficient Caco-2 cell model with differential incorporation of chemical or food forms of Se into GPx provides a new tool to study the cellular mechanisms of Se bioavailability.

  13. Assessment of functional and structural damage in brain parenchyma in patients with vitamin B12 deficiency: A longitudinal perfusion and diffusion tensor imaging study.

    PubMed

    Roy, Bhaswati; Trivedi, Richa; Garg, Ravindra K; Gupta, Pradeep K; Tyagi, Ritu; Gupta, Rakesh K

    2015-06-01

    Vitamin B12 deficiency may cause neural tissue damage. Even in advanced stages, conventional imaging of brain usually appears normal in vitamin B12 deficient patients. The aim of this study was to assess the structural and functional changes in brain of patients with vitamin B12 deficiency before and after six weeks of vitamin B12 supplementation using diffusion tensor imaging and pseudo-continuous arterial spin labelling (PCASL). MR imaging including DTI and PCASL and neuropsychological tests (NPT) were performed in 16 patients with vitamin B12 deficiency and 16 controls before and after 6weeks of therapy. Cerebral blood flow (CBF) derived from PCASL and DTI indices was calculated in brain of patients with vitamin B12 deficiency and controls. Patient with vitamin B12 deficiency showed altered neuropsychological scores and altered CBF as well as fractional anisotropy (FA) values in various brain regions as compared with controls. Both CBF values and neuropsychological scores showed complete reversibility at 6weeks post therapy. Though FA values showed significant recovery, it failed to show complete recovery. Our results suggest that micro-structural recovery lags behind functional recovery in patients with vitamin B12 deficiency following therapy and CBF change may be used as an early predictor of complete recovery in patients with B12 deficiency. Copyright © 2015. Published by Elsevier Inc.

  14. Comprehensive biometric, biochemical and histopathological assessment of nutrient deficiencies in gilthead sea bream fed semi-purified diets.

    PubMed

    Ballester-Lozano, Gabriel F; Benedito-Palos, Laura; Estensoro, Itziar; Sitjà-Bobadilla, Ariadna; Kaushik, Sadasivam; Pérez-Sánchez, Jaume

    2015-09-14

    Seven isoproteic and isolipidic semi-purified diets were formulated to assess specific nutrient deficiencies in sulphur amino acids (SAA), n-3 long-chain PUFA (n-3 LC-PUFA), phospholipids (PL), P, minerals (Min) and vitamins (Vit). The control diet (CTRL) contained these essential nutrients in adequate amounts. Each diet was allocated to triplicate groups of juvenile gilthead sea bream fed to satiety over an 11-week feeding trial period. Weight gain of n-3 LC-PUFA, P-Vit and PL-Min-SAA groups was 50, 60-75 and 80-85 % of the CTRL group, respectively. Fat retention was decreased by all nutrient deficiencies except by the Min diet. Strong effects on N retention were found in n-3 LC-PUFA and P fish. Combined anaemia and increased blood respiratory burst were observed in n-3 LC-PUFA fish. Hypoproteinaemia was found in SAA, n-3 LC-PUFA, PL and Vit fish. Derangements of lipid metabolism were also a common disorder, but the lipodystrophic phenotype of P fish was different from that of other groups. Changes in plasma levels of electrolytes (Ca, phosphate), metabolites (creatinine, choline) and enzyme activities (alkaline phosphatase) were related to specific nutrient deficiencies in PL, P, Min or Vit fish, whereas changes in circulating levels of growth hormone and insulin-like growth factor I primarily reflected the intensity of the nutritional stressor. Histopathological scoring of the liver and intestine segments showed specific nutrient-mediated changes in lipid cell vacuolisation, inflammation of intestinal submucosa, as well as the distribution and number of intestinal goblet and rodlet cells. These results contribute to define the normal range of variation for selected biometric, biochemical, haematological and histochemical markers.

  15. Assessing the status of iodine deficiency disorder (IDD) and associated factors in Wolaita and Dawro Zones School Adolescents, southern Ethiopia.

    PubMed

    Workie, Shimelash Bitew; Abebe, Yemane Gebremariam; Gelaye, Amha Admasie; Mekonen, Tefera Chane

    2017-04-18

    Iodine deficiency is the major preventable cause of irreversible mental retardation in the world. Ethiopia is a country with high prevalence of iodine deficiency disorders which continue to affect a large number of the country's population. The aim of the study was to assess the prevalence of iodine deficiency disorder in Wolaita and Dawuro zones. A descriptive, cross-sectional study was conducted in high school and preparatory students in Wolaita and Dawuro zones between April and May 2012. Data were collected from 718 school adolescents using pre-tested questionnaire through systematic random sampling technique. Data were entered and cleaned using Epi-info version 3.5.3 and then transported to SPSS version 20 for analysis. Bivariate and Multivariable logistic regression were done and the cut off value set was P < 0.05 as this is considered as statistically significant. The overall prevalence (total goiter rate) of goiter in study area was 351 (48.9%). Students with Grade-1 goiter were 265 (36.9%) while with Grade-2 goiter was 86 (11.9%). Females were by a long way vulnerable for goiter and accounts 60.9% with Pearson correlation coefficient 0.300, P value 0.0001. Generally, the occurrence of goiter in the study area was found to have statistical significant association with sex of respondents (being female) [AOR = 3.526; 95% CI (2.55-4.87)], climatic condition of resident (temperate climate) [AOR = 0.617; 95% CI (0.404-0.943)], frequency of iodized salt use [AOR = 0.484; 95% CI (0.317-0.739)] and consumption of cassava [AOR = 4.184; 95% CI (2.6-6.707)]. In general, the study revealed that iodine deficiency disorder was a serious public health concern. Nearly half of adolescent students in Wolaita and Dawuro zones were affected by goiter. Therefore, emphasis on a sustainable iodine intervention program targeted at population level, particularly at females is mandatory. Nutrition education along with adequate Universal Salt Iodization program is urgently

  16. Assessment of selenium and vitamin E deficiencies in dairy herds and clinical disease in calves.

    PubMed

    Zust, J; Hrovatin, B; Simundić, B

    1996-10-19

    Because of the very low concentrations of selenium in the dry matter of grass, grass silage, hay and maize silage Slovenian dairy herds need to be supplemented with selenium. Selenium in the form of mineral and feed mixtures maintained adequate mean (sd) blood serum selenium concentrations of 43.9 (27.6) to 65.3 (18.5) micrograms/litre in lactating cows, but in late lactation and in the dry period when only mineral mixtures were used, about 60 per cent of the cows had marginal serum selenium concentrations, mainly because of the low intake of the mineral supplement. In 18 herds which were either unsupplemented or irregularly supplemented with selenium, the mean (sd) concentrations in blood serum were 13.7 (5.5) micrograms/litre and 17.4 (9.2) micrograms/litre, respectively, for selenium and 2.98 (2.72) mg/litre and 1.62 (1.73) mg/litre for vitamin E, indicating that under extensive farming conditions in Slovenia the lack of both micronutrients may be responsible for nutritional muscular dystrophy in calves. Among 37 clinical cases, cardiorespiratory signs predominated in 25 of the calves and skeletal myopathy was dominant in 12. A very low mean serum selenium concentration [9.7 (7.2) micrograms/litre] and typically high activities of aspartate aminotransferase (AST) [1125 (373) U/litre] and creatine kinase (CK) [9169 (3681) U/litre) were observed for the myocardial form of the disease, and 2797 (550) U/litre and 22,650 (13,500) U/litre were observed for the skeletal form of the disease. A highly significant (P < 0.0001) difference in the selenium concentration of liver dry matter between the regularly supplemented [402 (207) micrograms/kg] and irregularly supplemented [173 (69) micrograms/kg] herds was observed. If a minimum value of 300 micrograms/kg of liver dry matter is accepted as the criterion for the determination of adequate selenium status, 93 per cent of the samples from the irregularly supplemented herds were selenium deficient. A similar proportion was

  17. Assessment of vitamin K deficiency in CF--how much sophistication is useful?

    PubMed

    Mosler, Katharina; von Kries, Rüdiger; Vermeer, Cees; Saupe, Jörg; Schmitz, Thomas; Schuster, Antje

    2003-06-01

    Due to maldigestion of dietary lipids, fat soluble vitamins are prone to malabsorption in cystic fibrosis (CF) patients with pancreatic insufficiency (PICF). Routine supplementation of vitamin K(1) in PICF is presently subject of discussion. Serum vitamin K, prothrombin time, PIVKA-II ('liver marker', by two different ELISAs), hydroxyapatite binding capacity (HBC, 'bone marker') and ApoE genotypes were measured in 32 PICF patients (age: 7 months to 25 years) with (PICFK) or without (PICFN) oral vitamin K(1) supplementation, all receiving lipase supplementation, and in 18 healthy controls (C). PIVKA-II was positive only in 4/7 PICFN. HBC medians of all groups were 57-60%. HBC values of PIVKA-II positive patients were below HBC median of their group. There was no correlation between HBC and PIVKA-II. There was no correlation between prothrombin time and other measurements. HBC medians with regard to ApoE were ApoE2/3 (62.9%)>ApoE3/3 (57.6%)>ApoE3/4+ApoE4/4=(56.65%). Vitamin K deficiency of liver or bone may occur independently. Prothrombin time is an insensitive marker. Individuals with ApoE4 allels might be more susceptible to osteopenia. As high expenditures are necessary to detect patients at risk, routine vitamin K supplementation for all PICF patients appears appropriate.

  18. Overview of hereditary angioedema caused by C1-inhibitor deficiency: assessment and clinical management.

    PubMed

    Bork, K; Davis-Lorton, M

    2013-02-01

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare, autosomal-dominant disease. HAE-C1-INH is characterized by recurrent attacks of marked, diffuse, nonpitting and nonpruritic skin swellings, painful abdominal attacks, and laryngeal edema. The extremities and the gastrointestinal tract are most commonly affected. Swelling of the upper respiratory mucosa poses the greatest risk because death from asphyxiation can result from laryngealedema. HAE-C1-INH attacks are variable, unpredictable, and may be induced by a variety of stimuli, including stress or physical trauma. Because the clinical presentation of HAE-C1-INH is similar to other types of angioedema, the condition may be a challenge to diagnose. Accurate identification of HAE-C1-INH is critical in order to avoid asphyxiation by laryngeal edema and to improve the burden of disease. Based on an understanding of the underlying pathophysiology of IHAE-C1-INH, drugs targeted specifically to the disease, such as C1-inhibitor therapy, bradykinin B2-receptor antagonists, and kallikrein-inhibitors, have become available for both treatment and prevention of angioedema attacks. This article reviews the clinical features, differential diagnosis, and current approaches to management of HAE-C1-INH.

  19. Metabolomics integrated with transcriptomics: assessing systems response to sulfur-deficiency stress.

    PubMed

    Hoefgen, Rainer; Nikiforova, Victoria J

    2008-02-01

    Sulfur-containing amino acids, cysteine and methionine synthesized in plants are essential for human and animal nutrition. That is why understanding of how inorganic sulfur is taken up by plants and built into the organic molecules in the process of sulfur assimilation is important. As complex biological systems, plants subsist as integrated molecular, organelle, cell, tissue and organ entities, being in permanent synergistic coordination. The process of sulfur uptake and assimilation is an integral part of this dense network of influences, its reconstruction may help in manipulating the bioproduction of organic sulfur-containing compounds. New high-throughput technologies allow the systems' view on the coordination of complex processes in living organisms. Among them, transcriptomics and metabolomics studies were applied to Arabidopsis plants subjected to sulfur-deficiency stress. From the integrated analysis of the obtained data, the mosaic picture of distinct sulfur stress response events and processes are starting to be assembled into the whole systems' network of sulfur assimilation. At the time trajectory of sulfur stress response, two system states can be distinguished. The first state of short-term responses is characterized by the development of enhanced lateral roots exploring the space in search for the lacking nutrient. When this physiological reaction cannot be accomplished by bringing the system back to the initial state of sulfur sufficiency, a new program is toggled aiming at saving the organismal resources for vital seed production. Here, we describe the biological reasoning in these two system states and the process of state transition between them.

  20. Acute and subacute toxicity assessment of lutein in lutein-deficient mice.

    PubMed

    Nidhi, Bhatiwada; Baskaran, Vallikannan

    2013-10-01

    Dietary lutein consumption is lower than the actual recommended allowances to prevent macular degeneration; thus dietary lutein supplements have been recommended. This study aimed to investigate potential adverse effect of lutein from Tagetes erecta in lutein-deficient (LD) male mice. Preliminary acute toxicity study revealed that the LD50 exceeded the highest dose of 10000 mg/kg BW. In a subacute study, male mice were gavaged with 0, 100, 1000 mg/kg BW/day for a period of 4 wk. Plasma lutein levels increased dose dependently (P < 0.01) after acute and subacute feeding of lutein in LD mice. Compared to the control (peanut oil without lutein) group, no treatment-related toxicologically significant effects of lutein were prominent in clinical observation, ophthalmic examinations, body, and organ weights. Further, no toxicologically significant findings were eminent in hematological, histopathological, and other clinical chemistry parameters. In the oral subacute toxicity study, the no-observed-adverse-effect level (NOAEL) for lutein in LD mice was determined as 1000 mg/kg/day, the highest dose tested. © 2013 Institute of Food Technologists®

  1. WTP Pretreatment Facility Potential Design Deficiencies--Sliding Bed and Sliding Bed Erosion Assessment

    SciTech Connect

    Hansen, E. K.

    2015-05-06

    This assessment is based on readily available literature and discusses both Newtonian and non-Newtonian slurries with respect to sliding beds and erosion due to sliding beds. This report does not quantify the size of the sliding beds or erosion rates due to sliding beds, but only assesses if they could be present. This assessment addresses process pipelines in the Pretreatment (PT) facility and the high level waste (HLW) transfer lines leaving the PT facility to the HLW vitrification facility concentrate receipt vessel.

  2. Quantitative Computerized Assessment of the Degree of Acetabular Bone Deficiency: Total radial Acetabular Bone Loss (TrABL)

    PubMed Central

    Gelaude, Frederik; Clijmans, Tim; Delport, Hendrik

    2011-01-01

    A novel quantitative, computerized, and, therefore, highly objective method is presented to assess the degree of total radical acetabular bone loss. The method, which is abbreviated to “TrABL”, makes use of advanced 3D CT-based image processing and effective 3D anatomical reconstruction methodology. The output data consist of a ratio and a graph, which can both be used for direct comparison between specimens. A first dataset of twelve highly deficient hemipelves, mainly Paprosky types IIIB, is used as illustration. Although generalization of the findings will require further investigation on a larger population, it can be assumed that the presented method has the potential to facilitate the preoperative use of existing classifications and related decision schemes for treatment selection in complex revision cases. PMID:22013539

  3. Gabrb3 gene deficient mice exhibit increased risk assessment behavior, hypotonia and expansion of the plexus of Locus coeruleus dendrites

    PubMed Central

    Hashemi, Ezzat; Sahbaie, Peyman; Davies, M. Frances; Clark, J. David; DeLorey, Timothy M.

    2007-01-01

    Gabrb3 gene deficient (gabrb3-/-) mice, control littermates (gabrb3+/+) and their progenitor strains, C57Bl/6J and 129/SvJ were assessed for changes in the morphology of the main noradrenergic nuclei, the locus coeruleus (LC) and LC-associated behaviors including anxiety and muscle tone. While the area defined by the cell bodies of the LC was found not to differ between gabrb3-/- mice and controls, the pericoerulear dendritic zone of the LC was found to be significantly enlarged in gabrb3-/- mice. Relative to controls, gabrb3-/- mice were also found to be hypotonic, as was indicated by poor performance on the wire hanging task. Gabrb3-/- mice also exhibited a significant increase in stretch-attend posturing, a form of risk assessment behavior associated with anxiety. However, in the plus maze, a commonly used behavioral test for assessing anxiety, no significant difference was observed between gabrb3-/- and control mice. Lastly, relative to controls, gabrb3-/- mice exhibited significantly less marble burying behavior, a method commonly used to assess obsessive-compulsive behavior. However, the poor marble burying performance of the gabrb3-/- mice could be associated with the hypotonic condition exhibited by these mice. In conclusion, the results of this study indicate that the gabrb3 gene contributes to LC noradrenergic dendrite development with the disruption of this gene in mice resulting in an enlarged plexus of LC dendrites with a concurrent reduction in muscle tone and marble burying behavior, an increase in risk assessment behavior but no change in the plus maze parameters that are commonly used for assessing anxiety. Section: Disease-related Neuroscience PMID:17156762

  4. Linkage Disequilibrium for Two X-Linked Genes in Sardinia and Its Bearing on the Statistical Mapping of the Human X Chromosome

    PubMed Central

    Filippi, G.; Rinaldi, A.; Palmarino, R.; Seravalli, E.; Siniscalco, M.

    1977-01-01

    The distribution of four X-linked mutants (G6PD, Deutan, Protan and Xg) among lowland and once highly malarial populations of Sardinia discloses a clear-cut example of linkage disequilibrium between two of them (G6PD and Protan). In the same populations the distribution of G6PD-deficiency versus colorblindness of the Deutan type and the Xg blood-group is not significantly different from that expected at equilibrium. These data suggest indirectly that the loci for G6PD and Protan may be nearer to one another than those for G6PD and Deutan. PMID:301840

  5. The Impact of Diagnosing Skill Deficiencies and Assessment-Based Communication Training on Managerial Performance.

    ERIC Educational Resources Information Center

    Papa, Michael J.; Graham, Elizabeth E.

    1991-01-01

    Evaluates an organizational diagnosis program that assesses managerial communication skills and provides the frame for follow-up training programs. Finds that managers participating in follow-up communication skills training performed significantly higher on interpersonal skills, problem-solving ability, and productivity over three long-term…

  6. Can selected functional movement screen assessments be used to identify movement deficiencies that could affect multidirectional speed and jump performance?

    PubMed

    Lockie, Robert G; Schultz, Adrian B; Jordan, Corrin A; Callaghan, Samuel J; Jeffriess, Matthew D; Luczo, Tawni M

    2015-01-01

    The Functional Movement Screen (FMS) includes lower-body focused tests (deep squat [DS], hurdle step, in-line lunge) that could assist in identifying movement deficiencies affecting multidirectional sprinting and jumping, which are important qualities for team sports. However, the hypothesized relationship with athletic performance lacks supportive research. This study investigated relationships between the lower-body focused screens and overall FMS performance and multidirectional speed and jumping capabilities in team sport athletes. Twenty-two healthy men were assessed in the FMS, and multidirectional speed (0- to 5-m, 0- to 10-m, 0- to 20-m sprint intervals; 505 and between-leg turn differences, modified T-test and differences between initial movement to the left or right); and bilateral and unilateral multidirectional jumping (vertical [VJ], standing long [SLJ], and lateral jump) tests. Pearson's correlations (r) were used to calculate relationships between screening scores and performance tests (p ≤ 0.05). After the determination of any screens relating to athletic performance, subjects were stratified into groups (3 = high-performing group; 2 = intermediate-performing group; 1 = low-performing group) to investigate movement compensations. A 1-way analysis of variance (p ≤ 0.05) determined any between-group differences. There were few significant correlations. The DS did moderately correlate with between-leg 505 difference (r = -0.423), and bilateral VJ (r = -0.428) and SLJ (r = -0.457). When stratified into groups according to DS score, high performers had a 13% greater SLJ when compared with intermediate performers, which was the only significant result. The FMS seems to have minimal capabilities for identifying movement deficiencies that could affect multidirectional speed and jumping in male team sport athletes.

  7. An infant and mother with severe B12 deficiency: vitamin B12 status assessment should be determined in pregnant women with anaemia.

    PubMed

    Sobczyńska-Malefora, A; Ramachandran, R; Cregeen, D; Green, E; Bennett, P; Harrington, D J; Lemonde, H A

    2017-08-01

    The vitamin B12 status of infants depends on maternal B12 status during pregnancy, and during lactation if breastfed. We present a 9-month-old girl who was admitted to the metabolic unit for assessment of developmental delay. She was exclusively breastfed and the introduction of solids at 5 months was unsuccessful. Investigations revealed pancytopenia, undetectable B12 and highly elevated methylmalonic acid and homocysteine. Methylmalonic acid and homocysteine normalised following B12 injections. Marked catch-up of developmental milestones was noted after treatment with B12. Investigations of parents showed normal B12 in the father and combined B12 and iron deficiency in the mother. Maternal B12 deficiency, most likely masked by iron deficiency, led to severe B12 deficiency in the infant. Exclusive breastfeeding and a subsequent failure to wean exacerbated the infant's B12 deficiency leading to developmental delay. This case highlights the need for development of guidelines for better assessment of B12 status during pregnancy.

  8. Determination of urinary iodine excretion to assess iodine deficiency level and iodine intake in primary school children, Bahir Dar, northwest Ethiopia.

    PubMed

    Bezabih, Belay; Assefa, Yihun; Yismaw, Gizachew; Mulu, Andargachew

    2007-10-01

    Iodine deficiency is a major public health problem all over the world, particularly among preschool children and pregnant women in low-income countries like Ethiopia and it is known to be the most common cause of preventable brain damage. to determine urinary iodine concentration and to assess the level of iodine deficiency disorders. A cross-sectional study was conducted in 386 randomly selected primary school children to determine urinary iodine concentrations as to assess level of iodine deficiency and iodine in take in Bahir Dar town. Median urinary iodine excretion was 58.8 mg/L (12.89 mg/L to 564.5 mg/L) which indicated the presence of mild iodine deficiency. Eighty seven percent of the children had urinary iodine excretion of below 100 mg/L and the intake of iodine was below 150 mg/day. Mild iodine deficiency disorder was found in Bahir Dar primary school children, Iodine intake was also found insufficient. Therefore, use of salt ionization should be advocated and strengthened.

  9. The Efficacy of Instructor-Guided Supplemental Instruction as a Strategy for Helping Reading-Deficient College Students Improve Testing and Assessment Outcomes

    ERIC Educational Resources Information Center

    Bartley-Lukula, Audrey

    2013-01-01

    This research project examined whether the use of Instructor-guided Supplemental Instruction as a classroom scaffolding technique, might help improve testing and assessment reading outcomes for reading-deficient college students. The study was completed at Tennessee State University in Nashville, Tennessee over the 16-week Fall, 2012 semester…

  10. The Efficacy of Instructor-Guided Supplemental Instruction as a Strategy for Helping Reading-Deficient College Students Improve Testing and Assessment Outcomes

    ERIC Educational Resources Information Center

    Bartley-Lukula, Audrey

    2013-01-01

    This research project examined whether the use of Instructor-guided Supplemental Instruction as a classroom scaffolding technique, might help improve testing and assessment reading outcomes for reading-deficient college students. The study was completed at Tennessee State University in Nashville, Tennessee over the 16-week Fall, 2012 semester…

  11. Copper deficiency in sheep: an assessment of relationship between concentrations of copper in serum and plasma.

    PubMed

    Laven, Ra; Smith, Sl

    2008-12-01

    To assess the relationship between concentrations of copper in serum and plasma in sheep. Concentrations of Cu were measured in paired serum and heparinised plasma samples collected from 110 sheep in nine flocks. Linear regression was used to evaluate whether flock or gender had a significant effect on the association between concentrations of Cu in serum and plasma. The individual results for concentrations of Cu in serum were then compared with those from plasma, using correlation and limits of agreement plotting. Concentrations of Cu in serum ranged from 7.3 to 22 (mean 14.0) micromol/L, while concentrations in plasma ranged from 9 to 27 (mean 16.3) micromol/L. On average, concentrations of Cu in serum were 2.3 micromol/L lower than in plasma. Over the range of values seen in this study, concentrations of Cu in plasma and serum were significantly correlated (r=0.89), and mean concentrations in serum were 87% of those in plasma. There was no effect of flock or gender on the relationship between concentrations of Cu in serum and plasma. Despite the significant correlation, there was marked variability between individual samples in the proportion of Cu that was lost during clotting, with the 95% limits of agreement for serum Cu ranging from 70 to 104% of the plasma concentration. As in cattle, the individual variability in the loss of Cu during clotting in sheep is too great for concentration of Cu in serum to be used as a substitute for that in plasma. When assessing the blood Cu pool as part of the diagnosis of Cu-responsive disease in sheep, the concentration of Cu in plasma should be measured in preference to that of serum. We suggest that a range of 4.5 to 9 micromol/L in plasma be used to define marginal Cu status in sheep.

  12. Hair ethyl glucuronide and serum carbohydrate deficient transferrin for the assessment of relapse in alcohol-dependent patients.

    PubMed

    Crunelle, Cleo L; Verbeek, Jef; Dom, Geert; Covaci, Adrian; Yegles, Michel; Michielsen, Peter; De Doncker, Mireille; Nevens, Frederik; Cappelle, Delphine; van Nuijs, Alexander L N; Neels, Hugo

    2016-05-01

    Ethyl glucuronide in hair (hEtG) and serum carbohydrate deficient transferrin (%CDT) are valuable markers for alcohol abuse, but their diagnostic accuracy to monitor abstinence and relapse is unclear. Here, we investigate to what extent repeated measurements of hEtG and %CDT can be used to monitor relapse in alcohol-dependent patients during abstinence treatment. HEtG and %CDT were measured in individuals starting treatment for alcohol dependence both at treatment entry and 3months later. Alcohol consumption and relapse episodes were recorded using the Time Line Follow Back and by alcohol breath and urine tests, and correlated with hEtG and %CDT measurements. Fifteen patients completed the study, of which nine had one or more relapses. Hair EtG and serum %CDT identified whether a relapse occurred in 78% and 57% of cases, respectively. Only hEtG correlated with the amount of alcohol consumed before treatment entry (Pearson r=0.92; p<0.001). The specificity of %CDT to assess abstinence during treatment was 100%. HEtG had a specificity of only 17%; however, in all patients who remained abstinent, hEtG decreased with >85% from initial values. Mean hEtG, but not %CDT, differed significantly between patients who relapsed and patients who remained abstinent (p=0.034). HEtG was more sensitive than serum %CDT to assess relapse in alcohol-dependent patients and was positively correlated with the amounts of alcohol consumed. In contrast, serum %CDT was more specific for assessing abstinence. We highlight the benefit of repeated measurements of hEtG and serum %CDT for monitoring abstinence during treatment. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  13. Associations between Red Cell Polymorphisms and Plasmodium falciparum Infection in the Middle Belt of Ghana

    PubMed Central

    Amoako, Nicholas; Asante, Kwaku Poku; Adjei, George; Awandare, Gordon A.; Bimi, Langbong; Owusu-Agyei, Seth

    2014-01-01

    Background Red blood cell (RBC) polymorphisms are common in malaria endemic regions and are known to protect against severe forms of the disease. Therefore, it is important to screen for these polymorphisms in drugs or vaccines efficacy trials. This study was undertaken to evaluate associations between clinical malaria and RBC polymorphisms to assess biological interactions that may be necessary for consideration when designing clinical trials. Method In a cross-sectional study of 341 febrile children less than five years of age, associations between clinical malaria and common RBC polymorphisms including the sickle cell gene and G6PD deficiency was evaluated between November 2008 and June 2009 in the middle belt of Ghana, Kintampo. G6PD deficiency was determined by quantitative methods whiles haemoglobin variants were determined by haemoglobin titan gel electrophoresis. Blood smears were stained with Giemsa and parasite densities were determined microscopically. Results The prevalence of clinical malarial among the enrolled children was 31.9%. The frequency of G6PD deficiency was 19.0% and that for the haemoglobin variants were 74.7%, 14.7%, 9.1%, 0.9% respectively for HbAA, HbAC, HbAS and HbSS. In Multivariate regression analysis, children with the HbAS genotype had 79% lower risk of malaria infection compared to those with the HbAA genotypes (OR = 0.21, 95% CI: 0.06–0.73, p = 0.01). HbAC genotype was not significantly associated with malaria infection relative to the HbAA genotype (OR = 0.70, 95% CI: 0.35–1.42, p = 0.33). G6PD deficient subgroup had a marginally increased risk of malaria infection compared to the G6PD normal subgroup (OR = 1.76, 95% CI: 0.98–3.16, p = 0.06). Conclusion These results confirm previous findings showing a protective effect of sickle cell trait on clinical malaria infection. However, G6PD deficiency was associated with a marginal increase in susceptibility to clinical malaria compared to children without

  14. Mechanical assessment of elastin integrity in fibrillin-1-deficient carotid arteries: implications for Marfan syndrome

    PubMed Central

    Ferruzzi, Jacopo; Collins, Melissa J.; Yeh, Alvin T.; Humphrey, Jay D.

    2011-01-01

    Aims Elastin is the primary component of elastic fibres in arteries, which contribute significantly to the structural integrity of the wall. Fibrillin-1 is a microfibrillar glycoprotein that appears to stabilize elastic fibres mechanically and thereby to delay a fatigue-induced loss of function due to long-term repetitive loading. Whereas prior studies have addressed some aspects of ageing-related changes in the overall mechanical properties of arteries in mouse models of Marfan syndrome, we sought to assess for the first time the load-carrying capability of the elastic fibres early in maturity, prior to the development of ageing-related effects, dilatation, or dissection. Methods and results We used elastase to degrade elastin in common carotid arteries excised, at 7–9 weeks of age, from a mouse model (mgR/mgR) of Marfan syndrome that expresses fibrillin-1 at 15–25% of normal levels. In vitro biaxial mechanical tests performed before and after exposure to elastase suggested that the elastic fibres exhibited a nearly normal load-bearing capability. Observations from nonlinear optical microscopy suggested further that competent elastic fibres not only contribute to load-bearing, they also increase the undulation of collagen fibres, which endows the normal arterial wall with a more compliant response to pressurization. Conclusion These findings support the hypothesis that it is an accelerated fatigue-induced damage to or protease-related degradation of initially competent elastic fibres that render arteries in Marfan syndrome increasingly susceptible to dilatation, dissection, and rupture. PMID:21730037

  15. External quality assessment of platelet disorder investigations: results of international surveys on diagnostic tests for dense granule deficiency and platelet aggregometry interpretation.

    PubMed

    Hayward, Catherine P M; Moffat, Karen A; Plumhoff, Elizabeth; Timleck, Marnie; Hoffman, Suzanne; Spitzer, Ernie; Van Cott, Elizabeth M; Meijer, Piet

    2012-09-01

    The quality of platelet aggregation and dense granule deficiency testing is important for diagnosing platelet function disorders. After a successful pilot exercise on diagnosing platelet dense granule deficiency by electron microscopy (EM), the North American Specialized Coagulation Laboratory Association (NASCOLA) has launched regular external quality assurance (EQA) for dense granule EM, as well as for the interpretation of platelet aggregation findings. EQA records were analyzed to assess performance. For EM EQA, between 2009 and 2011, there was excellent performance in distinguishing normal from dense granule-deficient samples and good (>70%) agreement on classifying most electron dense structures in platelets. For aggregation EQA, some normal variants were misclassified and overall case interpretations were more acceptable for rare disorders than for common findings. NASCOLA experiences with these EQAs indicate that there is a need to improve the quality of platelet disorder evaluations. For aggregometry interpretations, deficits in performance could be addressed by translating guideline recommendations into practice.

  16. Sleep deficiency on school days in Icelandic youth, as assessed by wrist accelerometry.

    PubMed

    Rognvaldsdottir, Vaka; Gudmundsdottir, Sigridur L; Brychta, Robert J; Hrafnkelsdottir, Soffia M; Gestsdottir, Sunna; Arngrimsson, Sigurbjorn A; Chen, Kong Y; Johannsson, Erlingur

    2017-05-01

    The purpose of this study was to objectively measure, with wrist-worn actigraphy, free-living sleeping patterns in Icelandic adolescents, and to compare sleep duration, sleep quality and clock times between school days (SchD) and non-school days (NSchD) and the association between sleep and body mass index (BMI). A cross-sectional study on 15.9-year-old (±0.3) adolescents from six schools in Reykjavík, Iceland, took place in the spring of 2015. Free-living sleep was measured on 301 subjects (122 boys and 179 girls) over seven days using wrist-worn actigraphy accelerometers. Total rest time (TRT), total sleep time (TST), sleep quality markers, and clock times for sleep were quantified and compared between SchD and NSchD and between the sexes, using paired and group t-tests as appropriate. Linear regression was used to assess the association between sleep parameters and BMI. On SchD, TST was 6.2 ± 0.7 h, with sleep efficiency (SLE) of 87.9 ± 4.4% for the group. On NSchD, TST increased to 7.3 ± 1.1 h (p < 0.001), although SLE decreased to 87.4 ± 4.7% (p < 0.05). On SchD and NSchD, 67% and 93% had bed times after midnight, respectively, and on SchD 10.7% met sleep recommendations (8 h/night). There was no association between BMI and average sleep parameters. The majority of Icelandic adolescents did not get the recommended number of hours of sleep, especially on SchD. While TST increased on NSchD, many participants still did not achieve the recommendations. These findings provide information on the sleep patterns of adolescents and may serve as reference for development of policies and interventions to promote better sleep practices. Copyright © 2017. Published by Elsevier B.V.

  17. Influence of biomechanical parameters on cranial cruciate ligament-deficient or -intact canine stifle joints assessed by use of a computer simulation model.

    PubMed

    Brown, Nathan P; Bertocci, Gina E; Marcellin-Little, Denis J

    2015-11-01

    OBJECTIVE To investigate the influence of 4 biomechanical parameters on canine cranial cruciate ligament (CrCL)-intact and -deficient stifle joints. SAMPLE Data for computer simulations of a healthy 5-year-old 33-kg neutered male Golden Retriever in a previously developed 3-D rigid body pelvic limb computer model simulating the stance phase during walking. PROCEDURES Canine stifle joint biomechanics were assessed when biomechanical parameters (CrCL stiffness, CrCL prestrain, body weight, and stifle joint friction coefficient) were altered in the pelvic limb computer simulation model. Parameters were incrementally altered from baseline values to determine the influence on stifle joint outcome measures (ligament loads, relative tibial translation, and relative tibial rotation). Stifle joint outcome measures were compared between CrCL-intact and -deficient stifle joints for the range of parameters evaluated. RESULTS In the CrCL-intact stifle joint, ligament loads were most sensitive to CrCL prestrain. In the CrCL-deficient stifle joint, ligament loads were most sensitive to body weight. Relative tibial translation was most sensitive to body weight, whereas relative tibial rotation was most sensitive to CrCL prestrain. CONCLUSIONS AND CLINICAL RELEVANCE In this study, computer model sensitivity analyses predicted that CrCL prestrain and body weight influenced stifle joint biomechanics. Cranial cruciate ligament laxity may influence the likelihood of CrCL deficiency. Body weight could play an important role in management of dogs with a CrCL-deficient stifle joint.

  18. Hemoglobin E and Glucose-6-Phosphate Dehydrogenase Deficiency and Plasmodium falciparum Malaria in the Chittagong Hill Districts of Bangladesh

    PubMed Central

    Shannon, Kerry L.; Ahmed, Sabeena; Rahman, Hafizur; Prue, Chai S.; Khyang, Jacob; Ram, Malathi; Zahirul Haq, M.; Chowdhury, Ashish; Akter, Jasmin; Glass, Gregory E.; Shields, Timothy; Nyunt, Myaing M.; Khan, Wasif A.; Sack, David A.; Sullivan, David J.

    2015-01-01

    Hemoglobin E is largely confined to south and southeast Asia. The association between hemoglobin E (HbE) and malaria is less clear than that of hemoglobin S and C. As part of a malaria study in the Chittagong Hill Districts of Bangladesh, an initial random sample of 202 individuals showed that 39% and 49% of Marma and Khyang ethnic groups, respectively, were positive for either heterozygous or homozygous hemoglobin E. In this group, 6.4% were also found to be severely deficient and 35% mildly deficient for glucose-6-phosphate dehydrogenase (G6PD). In a separate Plasmodium falciparum malaria case–uninfected control study, the odds of having homozygous hemoglobin E (HbEE) compared with normal hemoglobin (HbAA) were higher among malaria cases detected by passive surveillance than age and location matched uninfected controls (odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.07–46.93). The odds of heterozygous hemoglobin E (HbAE) compared with HbAA were similar between malaria cases and uninfected controls (OR = 0.71, 95% CI = 0.42–1.19). No association by hemoglobin type was found in the initial parasite density or the proportion parasite negative after 2 days of artemether/lumefantrine treatment. HbEE, but not HbAE status was associated with increased passive case detection of malaria. PMID:26101273

  19. Hemoglobin E and Glucose-6-Phosphate Dehydrogenase Deficiency and Plasmodium falciparum Malaria in the Chittagong Hill Districts of Bangladesh.

    PubMed

    Shannon, Kerry L; Ahmed, Sabeena; Rahman, Hafizur; Prue, Chai S; Khyang, Jacob; Ram, Malathi; Haq, M Zahirul; Chowdhury, Ashish; Akter, Jasmin; Glass, Gregory E; Shields, Timothy; Nyunt, Myaing M; Khan, Wasif A; Sack, David A; Sullivan, David J

    2015-08-01

    Hemoglobin E is largely confined to south and southeast Asia. The association between hemoglobin E (HbE) and malaria is less clear than that of hemoglobin S and C. As part of a malaria study in the Chittagong Hill Districts of Bangladesh, an initial random sample of 202 individuals showed that 39% and 49% of Marma and Khyang ethnic groups, respectively, were positive for either heterozygous or homozygous hemoglobin E. In this group, 6.4% were also found to be severely deficient and 35% mildly deficient for glucose-6-phosphate dehydrogenase (G6PD). In a separate Plasmodium falciparum malaria case-uninfected control study, the odds of having homozygous hemoglobin E (HbEE) compared with normal hemoglobin (HbAA) were higher among malaria cases detected by passive surveillance than age and location matched uninfected controls (odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.07-46.93). The odds of heterozygous hemoglobin E (HbAE) compared with HbAA were similar between malaria cases and uninfected controls (OR = 0.71, 95% CI = 0.42-1.19). No association by hemoglobin type was found in the initial parasite density or the proportion parasite negative after 2 days of artemether/lumefantrine treatment. HbEE, but not HbAE status was associated with increased passive case detection of malaria.

  20. Genetic Epidemiology of Glucose-6-Dehydrogenase Deficiency in the Arab World.

    PubMed

    Doss, C George Priya; Alasmar, Dima R; Bux, Reem I; Sneha, P; Bakhsh, Fadheela Dad; Al-Azwani, Iman; Bekay, Rajaa El; Zayed, Hatem

    2016-11-17

    A systematic search was implemented using four literature databases (PubMed, Embase, Science Direct and Web of Science) to capture all the causative mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD) in the 22 Arab countries. Our search yielded 43 studies that captured 33 mutations (23 missense, one silent, two deletions, and seven intronic mutations), in 3,430 Arab patients with G6PDD. The 23 missense mutations were then subjected to phenotypic classification using in silico prediction tools, which were compared to the WHO pathogenicity scale as a reference. These in silico tools were tested for their predicting efficiency using rigorous statistical analyses. Of the 23 missense mutations, p.S188F, p.I48T, p.N126D, and p.V68M, were identified as the most common mutations among Arab populations, but were not unique to the Arab world, interestingly, our search strategy found four other mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) that are unique to Arabs. These mutations were exposed to structural analysis and molecular dynamics simulation analysis (MDSA), which predicting these mutant forms as potentially affect the enzyme function. The combination of the MDSA, structural analysis, and in silico predictions and statistical tools we used will provide a platform for future prediction accuracy for the pathogenicity of genetic mutations.

  1. Glucose-6-phosphate dehydrogenase deficiency A- variant in febrile patients in Haiti.

    PubMed

    Carter, Tamar E; Maloy, Halley; von Fricken, Michael; St Victor, Yves; Romain, Jean R; Okech, Bernard A; Mulligan, Connie J

    2014-08-01

    Haiti is one of two remaining malaria-endemic countries in the Caribbean. To decrease malaria transmission in Haiti, primaquine was recently added to the malaria treatment public health policy. One limitation of primaquine is that, at certain doses, primaquine can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd). In this study, we genotyped two mutations (A376G and G202A), which confer the most common G6PDd variant in West African populations, G6PDd A-. We estimated the frequency of G6PDd A- in a sample of febrile patients enrolled in an on-going malaria study who represent a potential target population for a primaquine mass drug administration. We found that 33 of 168 individuals carried the G6PDd A- allele (includes A- hemizygous males, A- homozygous or heterozygous females) and could experience toxicity if treated with primaquine. These data inform discussions on safe and effective primaquine dosing and future malaria elimination strategies for Haiti.

  2. [Effects of water deficiency on mitochondrial functions and polymorphism of respiratory enzymes in plants].

    PubMed

    Rakhmankulova, Z F; Shuĭskaia, E V; Rogozhnikova, E S

    2013-01-01

    In plants, adaptive-compensatory responses to stress always entail additional energy expenditure. A suggestion was brought forward that in plants growing under conditions of water stress there is a relationship between genetic variability of respiratory enzymes and their functional significance. With Kochia prostrate (L.) Schrad. as a case study, intraspecies genetic polymorphism under the conditions of drought has been analyzed using typical protein markers which, considering their functional importance, can be viewed as respiratory enzymes. Out of eight protein markers examined, four enzymes were singled out for which dominating combination of genotypes Dia B (a), G6pd (a), Gdh (c), and Mdh A (a) was incidental. In all populations from arid and semiarid zone, these genotypes frequency of occurrence was in the range of 0.53-1.0, i.e., it comprised more than 50% of the whole variety of combinations. Thus, it seems plausible that this combination of genotypes can be an "adaptive collection" for K. prostrata populations growing in arid habitats. A characteristic feature of the picked out enzymes is their belonging to NAD(P)(+)-depending oxidoreductases that play a key role in functioning and redox-regulation of respiratory metabolism in course of adapting to water deficiency. It is suggested that the presence of such well-balanced co-adaptive genotype combinations, that provide enzymes important in terms of energetics, determine the formation of energetic and redox-balances during the process of adaptation to water stress.

  3. Genetic Epidemiology of Glucose-6-Dehydrogenase Deficiency in the Arab World

    PubMed Central

    Doss, C. George Priya; Alasmar, Dima R.; Bux, Reem I.; Sneha, P.; Bakhsh, Fadheela Dad; Al-Azwani, Iman; Bekay, Rajaa El; Zayed, Hatem

    2016-01-01

    A systematic search was implemented using four literature databases (PubMed, Embase, Science Direct and Web of Science) to capture all the causative mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD) in the 22 Arab countries. Our search yielded 43 studies that captured 33 mutations (23 missense, one silent, two deletions, and seven intronic mutations), in 3,430 Arab patients with G6PDD. The 23 missense mutations were then subjected to phenotypic classification using in silico prediction tools, which were compared to the WHO pathogenicity scale as a reference. These in silico tools were tested for their predicting efficiency using rigorous statistical analyses. Of the 23 missense mutations, p.S188F, p.I48T, p.N126D, and p.V68M, were identified as the most common mutations among Arab populations, but were not unique to the Arab world, interestingly, our search strategy found four other mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) that are unique to Arabs. These mutations were exposed to structural analysis and molecular dynamics simulation analysis (MDSA), which predicting these mutant forms as potentially affect the enzyme function. The combination of the MDSA, structural analysis, and in silico predictions and statistical tools we used will provide a platform for future prediction accuracy for the pathogenicity of genetic mutations. PMID:27853304

  4. Inhibition of Glucose-6-Phosphate Dehydrogenase Could Enhance 1,4-Benzoquinone-Induced Oxidative Damage in K562 Cells

    PubMed Central

    Cao, Meng; Yang, Wenwen; Sun, Fengmei; Xu, Cheng

    2016-01-01

    Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose-6-phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4-benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure. PMID:27656260

  5. Assessment of the value of a competitive protein binding radioassay of folic acid in the detection of folic acid deficiency.

    PubMed Central

    Bain, B J; Wickramasinghe, S N; Broom, G N; Litwinczuk, R A; Sims, J

    1984-01-01

    The diagnostic value of the Becton Dickinson Radioassay Kit (125I) for the the assay of red cell folate has been investigated. The assay was acceptable with regards to precision but was non-linear with changing packed cell volume. Sensitivity of the assay was satisfactory, with 24 of 25 folate deficient patients giving red cell folate values which fell below the reference range. Specificity of the assay in the detection of folate deficiency was less satisfactory. As with microbiological assays, a considerable proportion of vitamin B12 deficient patients had low red cell folate values. In addition, low concentrations were found in 12% of patients who were unlikely to be deficient in either vitamin B12 or folic acid. PMID:6470170

  6. Combined cobalamin and iron deficiency anemia: a diagnostic approach using a model based on age and homocysteine assessment.

    PubMed

    Remacha, Angel F; Sardà, M P; Canals, C; Queraltò, J M; Zapico, E; Remacha, J; Carrascosa, C

    2013-04-01

    Macrocytosis, the hallmark of cobalamin/folate deficiency anemia, is frequently absent. Clinicians have to be aware of coexisting conditions that can mask the macrocytosis expression of megaloblastic anemia, especially iron deficiency. The objective of this work was to investigate the degree of overlap between iron deficiency anemia (IDA) and cobalamin deficiency and to develop a predictive model for differentiating IDA from combined deficiency. A prospective case and control study was carried out to investigate vitamin B12 and folate status in iron deficiency anemia. A total of 658 patients were recruited, 41 of whom (6.2 %) were excluded. The remaining 617 subjects consisted of 130 controls and 487 with IDA. Low vitamin B12 (LB12) was considered when serum vitamin B12 was ≤200 pmol/L. High serum homocysteine (Hcy) was defined by Hcy >17 μM/L. A multivariate analysis (including a logistic regression) was performed to develop a diagnostic model. Low vitamin B12 levels were found in 17.8 % of IDA subjects. Ten out of 11 subjects (91 %) with IDA and serum vitamin B12 (B12) ≤100 pmol/L showed vitamin B12 deficiency. Moreover, vitamin B12 deficiency was demonstrated in 48 % of cases with IDA and B12 between 101 and 150 pmol/L and in 40 % with IDA and B12 between 151 and 200 pmol/, respectively. As a result of multivariate logistic analysis, neutrophil counts and age predicted subjects with vitamin B12 ≤200 and Hcy >17 μmol/L, [Formula: see text]. Using the age of 60 as a cutoff, sensitivity was 91 % (39 out of the 43 patients with vitamin B12 deficiency and IDA were identified). In summary, low vitamin B12 was found in 18 % of patients with IDA. Vitamin B12 deficiency was demonstrated in many patients with LB12 and IDA. Age over 60 years was used to separate patients with combined deficiency (sensitivity 91 %). Therefore, for a diagnostic purpose, serum vitamin B12 should be evaluated in IDA patients over 60 years. This diagnostic model needs to

  7. [Validity of carbohydrate-deficient transferrine (CDT) in assessing chronic abuse of ethyl alcohol in urban public transport workers].

    PubMed

    Fustinoni, Silvia; De Vecchi, M; Bordini, L; Todaro, A; Riboldi, L; Bertazzi, P A

    2009-01-01

    The aim of this study was to verify the ability of some chemical-clinical parameters, with particular emphasis on carbohydrate-deficient transferrin (CDT), in assessing chronic abuse of ethanol in a group of urban public transport workers. In the 512 subjects, public transport tram drivers, all males, who entered the study, information on the intake of alcoholic beverages was collected during the periodical health surveillance controls performed according to Italian legislation (DM88/99). In the study subjects the following clinical-chemical parameters were measured: CDT gamma-glutamyltransferase (GGT), mean corpuscular volume of erythrocytes (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT). The subjects were divided into five groups according to different levels of alcohol intake: non-drinkers, occasional drinkers, moderate drinkers, habitual drinkers and heavy drinkers. The median values of CDT GGT and MCV were higher in drinkers than in non-drinkers, with an increasing trend in proportion to the amount of ethanol ingested. The validity of each parameter in determining chronic abuse of ethyl alcohol was calculated taking as true the statement on alcohol intake made spontaneously by the subject. CDT was confirmed as the parameter with the best sensitivity and specificity: 90% and 98%, respectively, the negative predictive value was 99%, while the positive predictive power was 45%. The combination of CDT with GGT or MCV led to small improvements in the positive predictive ability, which reached 50% for CDT and MCV and 60% for CDT and GGT. Our results confirmed that, also in the workplace, CDT is the most important parameter for the diagnosis of chronic abuse of alcohol intake, but also showed that the positivity of this marker cannot be taken as certainty of abuse. The adoption of further diagnostic tools is therefore proposed, such as a specific questionnaire to collect information on alcohol intake, and in case of positive CDT a second

  8. Measurement of carbohydrate-deficient transferrin (CDT) in a general medical clinic: is this test useful in assessing alcohol consumption.

    PubMed

    Aithal, G P; Thornes, H; Dwarakanath, A D; Tanner, A R

    1998-01-01

    The aim of this study was to measure serum carbohydrate-deficient transferrin (CDT) in consecutive patients attending a general medical clinic with a range of alcohol intakes to determine its value in assessing such intake. Eighty-one consecutive patients (42 male, 39 female) aged 20-85 years (median = 49.5 years) attending an out-patient clinic were selected for the study. Each patient completed an alcohol diary detailing the units of alcohol consumed in the previous week, a CAGE questionnaire and an alcohol history, and underwent conventional blood tests including mean corpuscular volume (MCV), liver function tests, and gamma-glutamyl transferase (GGT). CDT was estimated using an enzyme immunoassay (CDTect, Pharmacia). The group comprised of 17 teetotallers, 28 light (<100 g/week), 23 moderate (100-400 g/week), and 13 heavy (>400 g/week) drinkers. Median serum CDT for heavy drinkers (25.5 U/l) was significantly higher than for the rest (median = 17 U/l, Kruskal-Wallis test, P = 0.01). Serum CDT correlated significantly with the CAGE score (Mann-Whitney test, P = 0.01), but poorly with alcohol diary records (r = 0.1, P = 0.4). However the correlations between GGT and diary records (r = 0.43, P = 0.001) and MCV with diary records (r = 0.5, P < 0.001) were significant. Sensitivity, specificity, and positive predictive value for elevated serum CDT were 69, 81 and 41% respectively in detecting heavy drinking. The positive predictive values for the various parameters were 43% for elevated serum GGT, 41% for raised erythrocyte MCV, and 75% for a positive score on the CAGE questionnaire. When a combination of the markers CDT, GGT, and MCV was used, elevation in two of the three markers detected heavy drinking with sensitivity of 85%, specificity of 88%, and positive predictive value of 61%. We conclude that, in out-patients with a wide range of alcohol intakes conventional markers such as serum GGT and erythrocyte MCV were more suitable than serum CDT for assessing

  9. Assessment of diagnostic and therapeutic approaches of Helicobacter pylori-associated iron deficiency and anemia in children with dyspeptic symptoms.

    PubMed

    El-Aziz Awad, Mohiee El-Deen; Amin, Saleh Mohamed; Abdou, Saied Mohamed

    2014-12-01

    This study assessed the diagnostic approaches of Helicobacter pylori (IP)-associated iron deficiency (ID) and anemia (IDA) in children with dyspeptic symptoms and evaluated the effect of simultaneous anti-H. pylori (anti-HIP) therapy and oral iron in comparison with each of anti? HP therapy and oral iron therapy alone, on iron status as assessed by serum soluble transferrin receptor (sTfR) level. Two hundreds children with dyspeptic symptoms were subjected to clinical evaluation, stool examination, CBC, biochemical assays for serum iron parameters and measurements of serum IgG antibodies to HP and serum sTfR level by ELISA. Sixty children were found to have HP. associated ID or IDA and were randomly divided into 3 groups (20 children each). GA received 2-week anti-HP therapy plus 90-day oral iron, and GB received 2-week anti-HP therapy alone whereas group C received 90-day oral iron alone. Re-evaluation of the 3 groups was performed after 3 months of treatment initiation by repeat CBC and serum sTfR level. Children (45%) were HP-seropositive. The mean values of serum sTfR were significantly higher in HP-positive group and in HP-positive children with IDA than in HP-negative group and in HP-negative children with IDA although no significant differences were noted in hematologic variables and iron parameters between the corresponding groups and children. As regard treatment groups, there were significant improvements in the mean values of indices of IDA status (HIb, MCH, MCV, sTfR) and ID status (sTtRi) at 3 months of treatment initiation compared with their baseline values after. anti-HP triple therapy either with oral iron or without oral iron whereas the control children who were treated with oral iron alone showed insignificant changes despite oral iron administration. The improvements in these parameters were significantly greater in groups of children who received anti-HP therapy either combined with iron or alone, where compared with those who did not receive

  10. Identification of a TXREB pseudogene (TXREBP) located between the genes for p55 (MPP1) and G6PD on Xq28

    SciTech Connect

    Das, S.; Gitschier, J. )

    1994-05-01

    A fibroblast cDNA library was screened by hybridization to a yeast artificial chromosome containing genomic sequences from human Xq28. The majority of positive cDNA clones were found to correspond to the cDNA coding for TXREB, an HTLV-1 enhancer-binding protein. Sequence analysis of the Xq28 genomic DNA revealed a number of deleterious changes compared to the previously reported cDNA. In addition, both the genomic DNA and cDNA isolates were found to be lacking a 599-bp sequence, bracketed by GT and AG, in the 5[prime] untranslated region. These results suggest that the Xq28-linked gene is a processed pseudogene for TXREB and that the previously reported cDNA was only partially processed. Southern blot analysis on a hybrid mapping panel confirmed the presence of at least one autosomal gene for TXREB, and Northern blot hybridization with the 599-bp putative intron probe confirmed that the sequence is not part of the mature mRNA. Further analysis showed that the gene is expressed in a variety of human tissues and that the pseudogene is located between the genes for the proteins p55 and G5PD. 7 refs., 3 figs.

  11. Disaccharidase deficiency.

    PubMed

    Bayless, T M; Christopher, N L

    1969-02-01

    This review of the literature and current knowledge concerning a nutritional disorder of disaccharidase deficiency discusses the following topics: 1) a description of disorders of disaccharide digestion; 2) some historical perspective on the laboratory and bedside advances in the past 10 years that have helped define a group of these digestive disorders; 3) a classification of conditions causing disaccharide intolerance; and 4) a discussion of some of the specific clinical syndromes emphasizing nutritional consequences of these syndromes. The syndromes described include congenital lactase deficiency, acquired lactase deficiency in teenagers and adults, acquired generalized disaccharidase deficiency secondary to diffuse mucosal damage, acquired lactose intolerance secondary to alterations in the intestinal transit, sucrase-isomaltase deficiencies, and other disease associations connected with lactase deficiency such as colitis.

  12. Pituitary deficiencies.

    PubMed

    Greco, Deborah S

    2012-02-01

    Diabetes insipidus, arising from damage to or congenital abnormalities of the neurohypophysis, is the most common pituitary deficiency in animals. Hypopituitarism and isolated growth hormone or thyrotropin deficiency may result in growth abnormalities in puppies and kittens. In addition, treatment of associated hormone deficiencies, such as hypothyroidism and hypoadrenocorticism, in patients with panhypopituitarism is vital to restore adequate growth in dwarfed animals. Secondary hypoadrenocorticism is an uncommon clinical entity; however differentiation of primary versus secondary adrenal insufficiency is of utmost importance in determining optimal therapy. This article will focus on the pathogenesis, diagnosis and treatment of hormone deficiencies of the pituitary gland and neurohypophysis. Copyright © 2012. Published by Elsevier Inc.

  13. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity

    PubMed Central

    Leopold, Jane A.; Dam, Aamir; Maron, Bradley A.; Scribner, Anne W.; Liao, Ronglih; Handy, Diane E.; Stanton, Robert C.; Pitt, Bertram; Loscalzo, Joseph

    2013-01-01

    Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanism by which aldosterone promotes endothelial dysfunction remains unknown. Glucose-6-phosphate dehydrogenase (G6pd), the principal source of Nadph, modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). In these studies, we show that aldosterone (10−9-10−7 mol/l) decreases endothelial G6pd expression and activity in vitro resulting in increased oxidant stress and decreased cGMP levels similar to what is observed in G6pd-deficient cells. Aldosterone decreases G6pd expression by protein kinase A activation to increase expression of Crem, which interferes with Creb binding to the G6pd promoter. In vivo, infusion of aldosterone decreases vascular G6pd expression and impairs vascular reactivity. These effects are abrogated by spironolactone or vascular gene transfer of G6pd. These studies demonstrate that aldosterone induces a G6pd-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6pd activity. PMID:17273168

  14. The association between subjective assessment of menstrual bleeding and measures of iron deficiency anemia in premenopausal African-American women: a cross-sectional study.

    PubMed

    Bernardi, Lia A; Ghant, Marissa S; Andrade, Carolina; Recht, Hannah; Marsh, Erica E

    2016-08-15

    Both iron deficiency and iron deficiency anemia are common in the United States with a prevalence amongst women of 12 % and 4 % respectively. These numbers are even higher in African-American women (AAW) and are often a result of heavy menstrual bleeding (HMB). The primary objective of this study was to determine if perceived assessment of menstrual bleeding was associated with objective and subjective measures of anemia in AAW. Quantitative cross-sectional pilot study with surveys and venipuncture. 44 premenopausal AAW (mean age 37.9 years ± 9. 4) participated in the study. Iron deficiency was present in 68.2 % of the participants and 18.2 % were anemic. Almost half of the participants reported that their menses were heavy or very heavy, and there was a relationship between perceived heaviness of menstrual flow and anemia (P = 0.021). Of the individuals who reported that their menses were heavy or very heavy, 35.0 % were anemic. AAW who reported heavy or very heavy menses had significantly lower hemoglobin (P = 0.015), hematocrit (P = 0.003), and ferritin (P = 0.012) levels, as well as more general (P = 0.006) and menses-associated symptoms of anemia (P = 0.015) than those who reported normal or light menses. This pilot study of premenopausal AAW found that a significant percentage of women who report HMB are not only iron deficient, but also anemic. AAW should be educated on the consequences of HMB and counseled to seek care with a women's health provider when they perceive HMB. More importantly, providers should be aware that when AAW report HMB, evaluation for iron deficiency and anemia are essential.

  15. In Silico Model-driven Assessment of the Effects of Brain-derived Neurotrophic Factor Deficiency on Glutamate and Gamma-Aminobutyric Acid: Implications for Understanding Schizophrenia Pathophysiology

    PubMed Central

    Agrawal, Rimjhim; Kalmady, Sunil Vasu; Venkatasubramanian, Ganesan

    2017-01-01

    Objective Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Methods Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)-Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA. Steady state stability, perturbation time-course simulation and sensitivity analysis were performed in COPASI after assigning the kinetic functions, optimizing the unknown parameters using random search and genetic algorithm. Results Study observations suggest that increased glutamate in hippocampus, similar to that seen in schizophrenia, could potentially be contributed by indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to impaired transport via vesicular glutamate transporter, thereby further increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and CREB regulated transcription coactivator-1 played significant role in this network. Conclusion The study presents in silico quantitative model of biochemical network constituting the key signaling molecules implicated in schizophrenia pathogenesis. It provides mechanistic insights into putative contribution of deficient BNDF towards alterations in neurotransmitters and

  16. In SilicoModel-driven Assessment of the Effects of Brain-derived Neurotrophic Factor Deficiency on Glutamate and Gamma-Aminobutyric Acid: Implications for Understanding Schizophrenia Pathophysiology.

    PubMed

    Agrawal, Rimjhim; Kalmady, Sunil Vasu; Venkatasubramanian, Ganesan

    2017-05-31

    Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)- Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA. Steady state stability, perturbation time-course simulation and sensitivity analysis were performed in COPASI after assigning the kinetic functions, optimizing the unknown parameters using random search and genetic algorithm. Study observations suggest that increased glutamate in hippocampus, similar to that seen in schizophrenia, could potentially be contributed by indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to impaired transport via vesicular glutamate transporter, thereby further increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and CREB regulated transcription coactivator-1 played significant role in this network. The study presents in silicoquantitative model of biochemical network constituting the key signaling molecules implicated in schizophrenia pathogenesis. It provides mechanistic insights into putative contribution of deficient BNDF towards alterations in neurotransmitters and neuroplasticity that are consistent with current

  17. Biotinylation of histones by human serum biotinidase: assessment of biotinyl-transferase activity in sera from normal individuals and children with biotinidase deficiency.

    PubMed

    Hymes, J; Fleischhauer, K; Wolf, B

    1995-10-01

    Serum biotinidase has biotinyl-transferase activity in addition to biocytin hydrolase activity. A sensitive assay for biotinyl-transferase activity was developed based on the transfer of biotin from biocytin to histones. Biotinidase biotinyl-transferase occurs at physiological and alkaline pHs, whereas hydrolysis of biocytin occurs optimally at pH 4.5 to 6.0. Measurement of hydrolysis requires micromolar concentrations of biocytin, whereas biotinylation of histones can be detected readily at 1.5 nM biocytin. Because polylysine is readily biotinylated by biotinidase in the presence of biocytin, whereas polyarginine is not, the enzyme likely transfers biotin to the epsilon-amino group of lysyl residues. To determine if patients who are deficient in biocytin hydrolase activity are also deficient in biotinyl-transferase activity, serum from 103 children (25 identified by exhibiting clinical symptoms and 78 detected by newborn screening) with profound biotinidase deficiency (less than 10% of mean normal biotinyl-p-aminobenzoate hydrolyzing activity) were assessed for biotinyl-transferase activity and for the presence of cross-reacting material (CRM) to antibodies prepared against purified serum biotinidase. Sera from all symptomatic patients, both CRM-negative and CRM-positive, had no biotinyl-transferase activity. Sera that was CRM-negative from children ascertained by newborn screening also had no biotinyl-transferase activity, whereas sera from 67% of the CRM-positive children identified by newborn screening had varying degrees of biotinyl-transferase activity. These results indicate that there is a large group of enzyme-deficient children detected by newborn screening who are different biochemically from those who are symptomatic. The clinical relevance of having some degree of biotinyl-transferase activity for individuals with biotinidase deficiency remains to be determined. In addition, it is important to determine if biotinyl-transferase activity, especially

  18. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 2, 0.02 Substructure

    SciTech Connect

    Not Available

    1993-05-01

    System information is given for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; system work breakdown structure; and general system/material data. System assembly/component deficiencies and inspection methods are given for slabs-on-grade, columns, and column fireproofing.

  19. Condition Assessment survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 9, 0.09 Electrical, Book 1

    SciTech Connect

    Not Available

    1993-05-01

    General information is presented for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; and system work breakdown structure. Deficiency standards are presented for service & distribution; lighting; and special systems.

  20. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 7, 0.07 Conveying

    SciTech Connect

    Not Available

    1993-05-01

    System information is given for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; and system work breakdown structure. Deficiency standards and inspection methods are presented for elevators and special conveyors.

  1. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 8, 0.08 Mechanical, Book 1

    SciTech Connect

    Not Available

    1993-05-01

    System information is presented for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet too & material listing; testing methods; inspection frequency; standard system design life tables; and system work breakdown structure. Deficiency standards are given for plumbing, fire protection, heating, cooling, and special (drinking water cooling systems).

  2. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 3, 0.03 Superstructure

    SciTech Connect

    Not Available

    1993-05-01

    General information is presented on asset determinant factor/CAS profile codes/CAS cost process; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; system work breakdown structure; and general system/material data. Deficiency standards and inspection methods are presented for beams; pre-engineered building systems; floors; roof structure; stairs; and fireproofing.

  3. Comparison of the Richmond HRR 4th edition and Farnsworth-Munsell 100 Hue Test for quantitative assessment of tritan color deficiencies.

    PubMed

    Foote, Katharina G; Neitz, Maureen; Neitz, Jay

    2014-04-01

    Drugs and environmental factors can induce tritan deficiencies. The Farnsworth-Munsell (FM) 100 Hue Test has become the gold standard in measuring these acquired defects. However, the test is time consuming, and color discrimination is confounded by concentration and patience. Here, we describe a test that compares six tritan plates from the HRR Pseudoisochromatic Plates 4th edition to 16 FM 100 Hue tritan caps. CIE Standard Illuminant C was reduced over five light intensities to simulate the effects of acquired losses in the S-cone pathway. Both tests showed quantitative differences in error rates with all light levels; thus they could serve equally well for assessing acquired deficiencies. However, compared to the FM 100, the HRR took subjects about 20-40 s per trial, making it more practical.

  4. Tafenoquine for preventing relapse in people with Plasmodium vivax malaria.

    PubMed

    Rajapakse, Senaka; Rodrigo, Chaturaka; Fernando, Sumadhya Deepika

    2015-04-29

    Plasmodium vivax malaria is widespread, and the persistent liver stage causes relapse of the disease which contributes to continued P. vivax transmission. Primaquine is currently the only drug that cures the parasite liver stage, but requires 14 days to be effective and can cause haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In addition, there is some evidence of parasite resistance to the drug. Tafenoquine is a new alternative with a longer half-life. To assess the effects of tafenoquine in people with P. vivax infection. We searched the following databases up to 13 April 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; CINAHL; SCOPUS; and LILACS. We also searched the World Health Organization (WHO) International Clinical Trial Registry Platform and the metaRegister of Controlled Trials (mRCT) for ongoing trials using "tafenoquine" and "malaria" as search terms up to 13 April 2015. Randomized controlled trials (RCTs) in people with P. vivax malaria. Adverse effects of tafenoquine are assessed in populations where people with G6PD deficiency have been excluded, and in populations without screening for G6PD deficiency. All review authors independently extracted data and assessed trial quality. Meta-analysis was carried out where appropriate, and estimates given as relative risk with 95% confidence intervals. We assessed the quality of the evidence using the GRADE approach. Three RCTs met our inclusion criteria, with the asexual infection in both the tafenoquine and comparator arm treated with chloroquine, and in all trials G6PD deficiency patients were excluded. Tafenoquine dose comparisonsThree of the included trials compared eight different dosing regimens. Tafenoquine doses of 300 mg and above resulted in fewer relapses than no hypnozoite treatment over six months follow-up in adults (300 mg single

  5. Assessment of the relative success of sporozoite inoculations in individuals exposed to moderate seasonal transmission

    PubMed Central

    Tall, Adama; Sokhna, Cheikh; Perraut, Ronald; Fontenille, Didier; Marrama, Laurence; Ly, Alioune B; Sarr, Fatoumata D; Toure, Aïssatou; Trape, Jean-François; Spiegel, André; Rogier, Christophe; Druilhe, Pierre

    2009-01-01

    Background The time necessary for malaria parasite to re-appear in the blood following treatment (re-infection time) is an indirect method for evaluating the immune defences operating against pre-erythrocytic and early erythrocytic malaria stages. Few longitudinal data are available in populations in whom malaria transmission level had also been measured. Methods One hundred and ten individuals from the village of Ndiop (Senegal), aged between one and 72 years, were cured of malaria by quinine (25 mg/day oral Quinimax™ in three equal daily doses, for seven days). Thereafter, thick blood films were examined to detect the reappearance of Plasmodium falciparum every week, for 11 weeks after treatment. Malaria transmission was simultaneously measured weekly by night collection of biting mosquitoes. Results Malaria transmission was on average 15.3 infective bites per person during the 77 days follow up. The median reappearance time for the whole study population was 46.8 days, whereas individuals would have received an average one infective bite every 5 days. At the end of the follow-up, after 77 days, 103 of the 110 individuals (93.6%; CI 95% [89.0–98.2]) had been re-infected with P. falciparum. The median reappearance time ('re-positivation') was longer in subjects with patent parasitaemia at enrolment than in parasitologically-negative individuals (58 days vs. 45.9; p = 0.03) and in adults > 30 years than in younger subjects (58.6 days vs. 42.7; p = 0.0002). In a multivariate Cox PH model controlling for the sickle cell trait, G6PD deficiency and the type of habitat, the presence of parasitaemia at enrolment and age ≥ 30 years were independently predictive of a reduced risk of re-infection (PH = 0.5 [95% CI: 0.3–0.9] and 0.4; [95% CI: 0.2–0.6] respectively). Conclusion Results indicate the existence of a substantial resistance to sporozoites inoculations, but which was ultimately overcome in almost every individual after 2 1/2 months of natural challenges

  6. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

    PubMed

    Mwaiswelo, Richard; Ngasala, Billy E; Jovel, Irina; Gosling, Roland; Premji, Zul; Poirot, Eugenie; Mmbando, Bruno P; Björkman, Anders; Mårtensson, Andreas

    2016-06-10

    This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Men and non-pregnant, non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. G6PD status was assessed using rapid test (CareStart™) and molecular genotyping. The primary endpoint was mean percentage relative reduction in haemoglobin (Hb) concentration (g/dL) between days 0 and 7 by genotypic G6PD status and treatment arm. Overall, 220 patients, 110 per treatment arm, were enrolled, of whom 33/217 (15.2 %) were phenotypically G6PD deficient, whereas 15/110 (13.6 %) were genotypically hemizygous males, 5/110 (4.5 %) homozygous females and 22/110 (20 %) heterozygous females. Compared to genotypically G6PD wild-type/normal [6.8, 95 % confidence interval (CI) 4.67-8.96], only heterozygous patients in AL arm had significant reduction in day-7 mean relative Hb concentration (14.3, 95 % CI 7.02-21.55, p=0.045), however, none fulfilled the pre-defined haemolytic threshold value of ≥25 % Hb reduction. After adjustment for baseline parasitaemia, Hb, age and sex the mean relative Hb reduction was not statistically significant in both heterozygous and hemizygous/homozygous patients in both arms. A majority of the adverse events (AEs) were mild and unrelated to the study drugs. However, six (4.4 %) episodes, three per treatment arm, of acute haemolytic anaemia occurred between days 0 and 7. Three occurred in phenotypically G6PD deficient

  7. Zinc deficiency.

    PubMed

    Tuerk, Melanie J; Fazel, Nasim

    2009-03-01

    Zinc plays an essential role in numerous biochemical pathways. Zinc deficiency affects many organ systems, including the integumentary, gastrointestinal, central nervous system, immune, skeletal, and reproductive systems. This article aims to discuss zinc metabolism and highlights a few of the diseases associated with zinc deficiency. Zinc deficiency results in dysfunction of both humoral and cell-mediated immunity and increases the susceptibility to infection. Supplementation of zinc has been shown to reduce the incidence of infection as well as cellular damage from increased oxidative stress. Zinc deficiency is also associated with acute and chronic liver disease. Zinc supplementation protects against toxin-induced liver damage and is used as a therapy for hepatic encephalopathy in patients refractory to standard treatment. Zinc deficiency has also been implicated in diarrheal disease, and supplementation has been effective in both prophylaxis and treatment of acute diarrhea. This article is not meant to review all of the disease states associated with zinc deficiency. Rather, it is an introduction to the influence of the many roles of zinc in the body, with an extensive discussion of the influence of zinc deficiency in selected diseases. Zinc supplementation may be beneficial as an adjunct to treatment of many disease states.

  8. A method for genotype validation and primer assessment in heterozygote-deficient species, as demonstrated in the prosobranch mollusc Hydrobia ulvae

    PubMed Central

    Brownlow, Robert J; Dawson, Deborah A; Horsburgh, Gavin J; Bell, James J; Fish, John D

    2008-01-01

    Background In studies where microsatellite markers are employed, it is essential that the primers designed will reliably and consistently amplify target loci. In populations conforming to Hardy-Weinberg equilibrium (HWE), screening for unreliable markers often relies on the identification of heterozygote deficiencies and subsequent departures from HWE. However, since many populations naturally deviate from HWE, such as many marine invertebrates, it can be difficult to distinguish heterozygote deficiencies resulting from unreliable markers from natural processes. Thus, studies of populations that are suspected to deviate from HWE naturally would benefit from a method to validate genotype data-sets and test the reliability of the designed primers. Levels of heterozygosity are reported for the prosobranch mollusc Hydrobia ulvae (Pennant) together with a method of genotype validation and primer assessment that utilises two primer sets for each locus. Microsatellite loci presented are the first described for the species Hydrobia ulvae; the five loci presented will be of value in further study of populations of H. ulvae. Results We have developed a novel method of testing primer reliability in naturally heterozygote deficient populations. After the design of an initial primer set, genotyping in 48 Hydrobia ulvae specimens using a single primer set (Primer set_A) revealed heterozygote deficiency in six of the seven loci examined. Redesign of six of the primer pairs (Primer set_B), re-genotyping of the successful individuals from Primer set_A using Primer set_B, and comparison of genotypes between the two primer sets, enabled the identification of two loci (Hulv-06 & Hulv-07) that showed a high degree of discrepancy between primer sets A and B (0% & only 25% alleles matching, respectively), suggesting unreliability in these primers. The discrepancies included changes from heterozygotes to homozygotes or vice versa, and some individuals who also displayed new alleles of

  9. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 12, 0.12 Sitework

    SciTech Connect

    Not Available

    1993-05-01

    General information is presented for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; system work breakdown structure; and general system/material data. Deficiency standards and inspection methods are given for utility distribution systems, central heating, central cooling, electrical, utility support structures, paving roadways/walkways, and tunnels.

  10. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 6, 0.06 Interior construction

    SciTech Connect

    Not Available

    1993-05-01

    General information is presented for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; system work breakdown structure; and general system/material data. Deficiency standards and inspection methods are presented for conventional and specialty partitions, toilet partitions & accessories, interior doors, paint finishes/coatings/ wall covering systems; floor finishing systems; and ceiling systems.

  11. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 5, 0.05 Roofing

    SciTech Connect

    Not Available

    1993-05-01

    General information is presented for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; and system work breakdown structure. Deficiency standards and inspection methods are presented for built-up membrane; single- ply membrane; metal roofing systems; coated foam membrane; shingles; tiles; parapets; roof drainage system; roof specialties; and skylights.

  12. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 11, 0.11 Specialty systems

    SciTech Connect

    Not Available

    1993-05-01

    General information is presented for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; system work breakdown structure; and general system/material data. Deficiency standards and inspection methods are presented for canopies; loading dock systems; tanks; domes (bulk storage, metal framing); louvers & vents; access floors; integrated ceilings; and mezzanine structures.

  13. Condition Assessment Survey (CAS) Program. Deficiency standards and inspections methods manual: Volume 1, 0.01 Foundations and footings

    SciTech Connect

    Not Available

    1993-05-01

    General information is presented for asset determinant factor/CAS repair codes/CAS cost factors; guide sheet tool & material listing; testing methods; inspection frequency; standard system design life tables; system work breakdown structure; and general system/material data. Deficiency standards and inspection methods are given for footings - spread/strip/grade beams; foundation walls; foundation dampproofing/waterproofing; excavation/backfill/ and piles & caissons.

  14. Flow cytometry analysis of adenosine deaminase (ADA) expression: a simple and reliable tool for the assessment of ADA-deficient patients before and after gene therapy.

    PubMed

    Otsu, Makoto; Hershfield, Michael S; Tuschong, Laura M; Muul, Linda M; Onodera, Masafumi; Ariga, Tadashi; Sakiyama, Yukio; Candotti, Fabio

    2002-02-10

    Clinical gene therapy trials for adenosine deaminase (ADA) deficiency have shown limited success of corrective gene transfer into autologous T lymphocytes and CD34(+) cells. In these trials, the levels of gene transduction and expression in hematopoietic cells have been assessed by DNA- or RNA-based assays and measurement of ADA enzyme activity. Although informative, these methods are rarely applied to clonal analysis. The results of these assays therefore provide best estimates of transduction efficiency and gene expression in bulk populations based on the assumption that gene transfer and expression are uniformly distributed among transduced cells. As a useful additional tool for evaluation of ADA gene expression, we have developed a flow cytometry (fluorescence-activated cell sorting, FACS) assay capable of estimating the levels of intracellular ADA on a single-cell basis. We validated this technique with T cell lines and peripheral blood mononuclear cells (PBMCs) from ADA-deficient patients that showed severely reduced levels of ADA expression (ADA-dull) by FACS and Western blot analyses. After retrovirus-mediated ADA gene transfer, these cells showed clearly distinguishable populations exhibiting ADA expression (ADA-bright), thus allowing estimation of transduction efficiency. By mixing ADA-deficient and normal cells and using enzymatic amplification, we determined that our staining procedure could detect as little as 5% ADA-bright cells. This technique, therefore, will be useful to quickly assess the expression of ADA in hematopoietic cells of severe combined immunodeficient patients and represents an important tool for the follow-up of patients treated in clinical gene transfer protocols.

  15. Iron deficiency: definition and diagnosis.

    PubMed

    Cook, J D; Skikne, B S

    1989-11-01

    There has been a continuous refinement over the past several decades of methods to detect iron deficiency and assess its magnitude. The optimal combination of measurements differs for clinical and epidemiological assessment. Clinically, the major problem is to distinguish true iron deficiency from other causes of iron-deficient erythropoiesis, such as the anaemia of chronic disease. Epidemiologically, techniques that provide quantified estimates of body iron are preferable. For both purposes, the serum ferritin is the focal point of the laboratory detection of iron deficiency. Serum ferritin measurements provide a reliable index of body iron stores in healthy individuals, a cost-effective method of screening for iron deficiency, and a useful alternative to bone marrow examinations in the evaluation of anaemic patients. Preliminary studies indicate that measurement of the serum transferrin receptor may be the most reliable way to assess deficits in tissue iron supply.

  16. An assessment of bone mineral density in patients with Addison's disease and isolated ACTH deficiency treated with glucocorticoid.

    PubMed

    Chikada, Naoko; Imaki, Toshihiro; Hotta, Mari; Sato, Kanji; Takano, Kazue

    2004-06-01

    Glucocorticoid replacement therapy needs to be tailored to individual patient's requirements in order to avoid risk of over or under medication. We measured bone mineral density (BMD) of lumbar spine using dual X-ray absorptiometory in 10 patients with Addison's disease and 5 patients with isolated ACTH deficiency receiving glucocorticoid replacement therapy. We also examined the effect of glucocorticoid replacement on BMD. Decreased %BMD (less than 80% of age-matched controls) was found in 2 female patients who had received hydrocortisone at a dose of 14.8 and 15.4 mg/m(2)/day. In contrast, no patient receiving a hydrocortisone dose of less than 12.4 mg/m (2)/day had decreased %BMD. There was no correlation between %BMD and hydrocortisone dose (mg/m(2)), duration of therapy, or cumulative hydrocortisone dose when treated with appropriate dose of hydrocortisone (<13.6 mg/m(2)). There was also no statistically significant difference in %BMD with age. We concluded that long-term glucocorticoid replacement therapy does not induce bone loss in patients with glucocorticoid deficiency unless an excessive dose of hydrocortisone is given.

  17. Food Versus Pharmacy: Assessment of Nutritional and Pharmacological Strategies to Improve Bone Health in Energy-Deficient Exercising Women.

    PubMed

    Southmayd, Emily A; Hellmers, Adelaide C; De Souza, Mary Jane

    2017-08-22

    The review aims to summarize our current knowledge surrounding treatment strategies aimed at recovery of bone mass in energy-deficient women suffering from the Female Athlete Triad. The independent and interactive contributions of energy status versus estrogen status on bone density, geometry, and strength have recently been reported, highlighting the importance of addressing both energy and estrogen in treatment strategies for bone health. This is supported by reports that have identified energy-related features (low body weight and BMI) and estrogen-related features (late age of menarche, oligo/amenorrhea) to be significant risk factors for low bone mineral density and bone stress injury in female athletes and exercising women. Nutritional therapy is the recommended first line of treatment to recover bone mass in energy-deficient female athletes and exercising women. If nutritional therapy fails after 12 months or if fractures or significant worsening in BMD occurs, pharmacological therapy may be considered in the form of transdermal estradiol with cyclic oral progestin (not COC).

  18. Cobalamin deficiency.

    PubMed

    Herrmann, Wolfgang; Obeid, Rima

    2012-01-01

    Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor

  19. Tafenoquine for preventing relapse in people with Plasmodium vivax malaria

    PubMed Central

    Rajapakse, Senaka; Rodrigo, Chaturaka; Fernando, Sumadhya Deepika

    2015-01-01

    Background Plasmodium vivax malaria is widespread, and the persistent liver stage causes relapse of the disease which contributes to continued P. vivax transmission. Primaquine is currently the only drug that cures the parasite liver stage, but requires 14 days to be effective and can cause haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficienc