scholarly journals Severe-glucose-6-phosphate dehydrogenase (G6PD) deficiency associated with chronic hemolytic anemia, granulocyte dysfunction, and increased susceptibility to infections: description of a new molecular variant (G6PD Barcelona)

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 428-434
Author(s):  
JL Vives Corrons ◽  
E Feliu ◽  
MA Pujades ◽  
F Cardellach ◽  
C Rozman ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
G6pd Deficiency ◽  
Specific Activity ◽  
Heat Stability ◽  
Molecular Characteristics ◽  
Functional Studies ◽  
Leukocyte Alkaline Phosphatase ◽  
Severe Deficiency ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Increased Susceptibility

Molecular, kinetic, and functional studies were carried out on erythrocytes and leukocytes in a Spanish male with G6PD deficiency, congenital nonspherocytic hemolytic anemia (CNSHA), and increased susceptibility to infections. G6PD activity was absent in patient's red cells and was about 2% of normal in leukocytes. Molecular studies using standard methods (WHO, 1967) showed G6PD in the patient to have a slightly fast electrophoretic mobility at pH 8.0 with otherwise normal properties (heat stability at 46 degrees C, apparent affinity for substrates, optimum pH, and utilization of substrate analogues). Other tests showed the patient's granulocytes to engulf latex particles normally, but to have impaired reduction of nitroblue tetrazolium and ferricytochrome-c as well as reduced iodination. Chemotaxis and random migration of the patient's granulocytes were normal as were myeloperoxidase, leukocyte alkaline phosphatase (LAP), and ultrastructural features. The molecular characteristics of G6PD in the patient differed from those of all previously reported variants associated with CNSHA, so the present variant was provisionally called G6PD Barcelona to distinguish it from other G6PD variants previously described. Possible mechanisms for the severe deficiency of G6PD in erythrocytes and granulocytes was investigated by studies on the immunologic specific activity of the mutant enzyme.

Severe-glucose-6-phosphate dehydrogenase (G6PD) deficiency associated with chronic hemolytic anemia, granulocyte dysfunction, and increased susceptibility to infections: description of a new molecular variant (G6PD Barcelona)

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 428-434 ◽  
Author(s):  
JL Vives Corrons ◽  
E Feliu ◽  
MA Pujades ◽  
F Cardellach ◽  
C Rozman ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
G6pd Deficiency ◽  
Specific Activity ◽  
Heat Stability ◽  
Molecular Characteristics ◽  
Functional Studies ◽  
Leukocyte Alkaline Phosphatase ◽  
Severe Deficiency ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Increased Susceptibility

Abstract Molecular, kinetic, and functional studies were carried out on erythrocytes and leukocytes in a Spanish male with G6PD deficiency, congenital nonspherocytic hemolytic anemia (CNSHA), and increased susceptibility to infections. G6PD activity was absent in patient's red cells and was about 2% of normal in leukocytes. Molecular studies using standard methods (WHO, 1967) showed G6PD in the patient to have a slightly fast electrophoretic mobility at pH 8.0 with otherwise normal properties (heat stability at 46 degrees C, apparent affinity for substrates, optimum pH, and utilization of substrate analogues). Other tests showed the patient's granulocytes to engulf latex particles normally, but to have impaired reduction of nitroblue tetrazolium and ferricytochrome-c as well as reduced iodination. Chemotaxis and random migration of the patient's granulocytes were normal as were myeloperoxidase, leukocyte alkaline phosphatase (LAP), and ultrastructural features. The molecular characteristics of G6PD in the patient differed from those of all previously reported variants associated with CNSHA, so the present variant was provisionally called G6PD Barcelona to distinguish it from other G6PD variants previously described. Possible mechanisms for the severe deficiency of G6PD in erythrocytes and granulocytes was investigated by studies on the immunologic specific activity of the mutant enzyme.

scholarly journals Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase–deficient children receiving dapsone

Blood ◽  
2012 ◽  
Vol 120 (20) ◽  
pp. 4123-4133 ◽  
Author(s):  
Allan Pamba ◽  
Naomi D. Richardson ◽  
Nick Carter ◽  
Stephan Duparc ◽  
Zul Premji ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Hemolytic Anemia ◽  
G6pd Deficiency ◽  
Case Reports ◽  
Drug Induced ◽  
Once Daily ◽  
Maximum Decrease ◽  
Life Threatening ◽  
The Mean ◽  
Glucose 6 Phosphate Dehydrogenase

AbstractDrug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging −2.64 g/dL (range −6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference −1.46 g/dL; 95% confidence interval −1.76, −1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was −1.83 g/dL (range +0.90 to −5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A− variant, ie, mutations V68M and N126D. Drug-induced acute hemolytic anemia in G6PD A− subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A− type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735.

scholarly journals Glucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype–phenotype association throughout an activity distribution

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ying He ◽  
Yinhui Zhang ◽  
Xionghao Chen ◽  
Qiong Wang ◽  
Lifen Ling ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
G6pd Deficiency ◽  
National Level ◽  
Gene Mutations ◽  
Single Mutation ◽  
Missense Mutations ◽  
Severe Deficiency ◽  
Compound Mutation ◽  
Normal Males ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common hereditary disorder in China. The existing prevalence and molecular epidemiology of G6PD deficiency in China were geographically limited. In this study, the spectrum of G6PD gene mutations was well characterized in a large and diverse population all over the country; and the correlation of genotype and enzyme activity phenotype was explored for the first time. The results showed that the overall prevalence of G6PD deficiency in China was 2.10% at the national level. The top six common mutations were c.1388 G>A, c.1376 G>T, c.95 A>G, c.392 G>T, c.871 G>A and c.1024 C>T, accounting for more than 90% of G6PD deficient alleles. Compound mutation patterns were frequently observed in females with severe deficiency. The distribution of G6PD activities depended on the type of mutation patterns and genders. Hemizygote, homozygote, and compound heterozygote were predominantly associated with severe G6PD deficiency, whereas heterozygotes with single mutation mainly presented moderate enzyme deficiency. A significant gap between G6PD activities in hemizygous and normal males was observed, and yet, the overall distribution of that in females carrying missense mutations was a continuum from G6PD severely deficient to normal. This is the first report of discussing the association between G6PD genetic variants in the Chinese and enzyme activity phenotypes.

Chronic nonspherocytic hemolytic anemia (CNSHA) and glucose 6 phosphate dehydrogenase (G6PD) deficiency in a patient with familial amyloidotic polyneuropathy (FAP)

1989 ◽  
Vol 81 (2) ◽  
pp. 161-164 ◽  
Author(s):  
Joan Lluis Vives-Corrons ◽  
M. Assumpci� Pujades ◽  
Josep Petit ◽  
Dolors Colomer ◽  
Montserrat Corbella ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
G6pd Deficiency ◽  
Familial Amyloidotic Polyneuropathy ◽  
Glucose 6 Phosphate Dehydrogenase

scholarly journals A New Variant of Glucose-6-Phosphate Dehydrogenase Deficiency Hereditary Hemolytic Anemia, G6PD Cornell: Erythrocyte, Leukocyte, and Platelet Studies

Blood ◽  
1974 ◽  
Vol 44 (3) ◽  
pp. 323-331 ◽  
Author(s):  
Denis R. Miller ◽  
Michael R. Wollman
Keyword(s):  
Hemolytic Anemia ◽  
Dehydrogenase Deficiency ◽  
Normal Values ◽  
White Male ◽  
Heat Stability ◽  
Ph Optimum ◽  
Substrate Analogues ◽  
New Variant ◽  
Normal Enzyme ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract A variant of glucose-6-phosphate-dehydrogenase deficiency associated with chronic hereditary hemolytic anemia was discovered in a 9-yr-old white male. The erythrocytes contained 5% of normal enzyme activity, the Km NADP was two to three times normal, the pH optimum was decreased, and the heat stability was markedly decreased. The Km G6PD, electrophoretic mobility (B), and utilization of substrate analogues 2-deoxy-G6P and deamino-NADP were normal. The activity of G6PD in the leukocytes and platelets was 15% and 28% of normal values, respectively, but bactericidal activity and platelet function were unaffected by the deficiency of G6PD.

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

2016 ◽  
Vol 60 (10) ◽  
pp. 5906-5913 ◽  
Author(s):  
Kristina S. Wickham ◽  
Paul C. Baresel ◽  
Sean R. Marcsisin ◽  
Jason Sousa ◽  
Chau T. Vuong ◽  
...  
Keyword(s):  
Single Dose ◽  
Malaria Transmission ◽  
Hemolytic Anemia ◽  
G6pd Deficiency ◽  
Safety Data ◽  
Vehicle Control ◽  
Control Group ◽  
Vehicle Control Group ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Dose Dependent

ABSTRACTIndividuals 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.

scholarly journals Rasburicase-induced Hemolytic Anemia in an Adolescent With Unknown Glucose-6-Phosphate Dehydrogenase Deficiency

2017 ◽  
Vol 22 (6) ◽  
pp. 471-471 ◽  
Author(s):  
Manzilat Akande ◽  
Anthony N. Audino ◽  
Joseph D. Tobias
Keyword(s):  
Hemolytic Anemia ◽  
G6pd Deficiency ◽  
Dehydrogenase Deficiency ◽  
Tumor Lysis Syndrome ◽  
Turnaround Time ◽  
Lymphoblastic Lymphoma ◽  
Test Results ◽  
Tumor Lysis ◽  
Prevention And Treatment ◽  
Glucose 6 Phosphate Dehydrogenase

Rasburicase, used in the prevention and treatment of tumor lysis syndrome (TLS), may cause hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Although routine screening for G6PD deficiency has been recommended, given the turnaround time for test results and the urgency to treat TLS, such screening may not be feasible. We report a case of rasburicase-induced hemolytic anemia without methemoglobinemia in an adolescent with T-cell lymphoblastic lymphoma, TLS, and previously unrecognized G6PD deficiency. Previous reports of hemolytic anemia with rasburicase are reviewed, mechanisms discussed, and preventative strategies presented.

scholarly journals Hereditary nonspherocytic hemolytic anemia due to a new hexokinase variant with reduced stability

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 690-697 ◽  
Author(s):  
M Magnani ◽  
V Stocchi ◽  
L Cucchiarini ◽  
G Novelli ◽  
S Lodi ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Specific Activity ◽  
Blood Platelets ◽  
Phenotypic Variability ◽  
Ph Dependence ◽  
Glucose Consumption ◽  
Heat Stability ◽  
Normal Activity ◽  
Red Cell ◽  
Hexokinase Activity

A 27-year-old woman with severe chronic hemolytic anemia was found to have reduced red cell hexokinase activity when the degree of reticulocytosis was considered. This enzyme had normal pH-dependent activity, normal Km for glucose, fructose, and mannose, normal Km for Mg adenosine triphosphate (ATP)2- and Ki for glucose-1,6-diphosphate. Furthermore, the pH-dependence and orthophosphate dependence of Ki for glucose-1,6-diphosphate were normal. However, this hexokinase was inactivated rapidly at 44 degrees C. No abnormalities were found in the red cell hexokinase isozymic pattern when it was compared with the profile obtained from cells of similar age. The hexokinase specific activity was reduced in all the red blood cell fractions obtained by density gradient ultracentrifugation; a marked difference in the distribution of cells through the gradient was evident. Among the glycolytic intermediates, a significant decrease of 2,3- diphosphoglycerate was evident. ATP and glucose 6-phosphate were also reduced when compared with cells of similar. Glucose consumption of the hexokinase-deficient cells decreased, but the rate of glucose metabolized through the hexose monophosphate shunt was unchanged. Although the total hexokinase activity in lymphocytes was only reduced by 37%, a marked hexokinase deficiency was detected in blood platelets (20% to 25% of normal activity). The parents and one of two siblings of the patient were heterozygous for the defect, with 66% to 74% of normal erythrocyte hexokinase activity and reduced heat stability of the enzyme. These results, when compared with those obtained in previously reported cases of hexokinase deficiency, provide further evidence of the broad phenotypic variability that characterizes this disorder. Furthermore, it is suggested that failure of energy generation is probably the primary cause of hemolytic anemia in hexokinase deficiency.

scholarly journals A Philippino Glucose-6-Phosphate Dehydrogenase Variant (G6PD Union) With Enzyme Deficiency and Altered Substrate Specificity

Blood ◽  
1970 ◽  
Vol 35 (4) ◽  
pp. 506-513 ◽  
Author(s):  
AKIRA YOSHIDA ◽  
ERNST W. BAUR ◽  
ARNO G. MOUTLSKY
Keyword(s):  
Substrate Specificity ◽  
Specific Activity ◽  
Cell Enzyme ◽  
Severe Deficiency ◽  
Genetic Pattern ◽  
Normal Enzyme ◽  
Place Of Origin ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Variant Enzyme ◽  
G6pd Variant

Abstract A variant of glucose-6-phosphate dehydrogenase (G6PD) associated with altered substrate specificity and severe deficiency of red cell enzyme activity was found in a Philippino male and in his relatives. The genetic pattern was consistent with X-linked inheritance. α-Thalassemia was found in the propositus and in several family members, but there was no interaction between G6PD deficiency and α-thalassemia. This G6PD variant has two pH optima, at pH 5.5 and pH 9.0, while the normal enzyme is inactive at pH 5.5. The substrate specificity of the variant enzyme is different from any known G6PD variant: 2-deoxyglucose-6-phosphate and galactose-6-phosphate are good substrates and deamino-NADP is a better coenzyme than NADP. Although G6PD activity in the variant red cells was only three per cent of normal, quantitative immunologic neutralization suggested that the specific activity of the variant enzyme might be at least ten per cent of that of the normal enzyme. This variant is named after the place of origin, Gd Union.

scholarly journals Effects of vitamin E supplementation on some aspects of hematological variables in patients of hemolytic anemia with glucose 6 phosphate dehydrogenase (G6PD) deficiency

1970 ◽  
pp. 12-17 ◽  
Author(s):  
Nayma Sultana ◽  
Noorzahan Begum ◽  
Shelina Begum ◽  
Sultana Ferdousi ◽  
Taskina Ali
Keyword(s):  
Vitamin E ◽  
Hemolytic Anemia ◽  
G6pd Deficiency ◽  
Serum Bilirubin ◽  
Reticulocyte Count ◽  
Healthy Control ◽  
Hb Concentration ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Vitamin E Supplementation

Vitamin E works within the cell membrane as a biological antioxidant and may prevent premature destruction of RBC in Glucose 6-phosphate dehydrogenase (G6PD) deficient hemolytic anemia. Changes in some of the hematological variables like hemoglobin (Hb) concentration, total count (TC) of RBC, packed cell volume (PCV) and reticulocyte counts may occur due to hemolysis of RBC in G6PD deficiency In the present study the role of vitamin E supplementation on these changes were observed in reducing chronic hemolysis in anemic patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency For this, a total number of 102 subjects with age ranged from 5 to 40 years of both sexes were included in the study Among them 68 were G6PD enzyme deficient patients, of whom 34 were in supplemented group (experimental group) and 34 were nonsupplemented group (control group). The supplemented group received vitamin E supplementation for 60 consecutive days at a dose of 800 IU/day for adult and 400 IU/day for children 5. 12 years (in a divided dose i,e. 4 times daily). Age and sex matched 34 apparently healthy subjects with normal blood G6PD level were taken to observe the baseline data (healthy control) and also for comparison. All the G6PD deficient patients were selected from Out Patient Department (OPD) of hematology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh during the period of July 2005 to June 2006 and all the healthy subjects were selected from personal contact. Blood G6PD level, Hb%, TC of RBC, PCV, reticulocyte count and serum bilirubin level of all subjects were measured by standard laboratory techniques. All the parameters were measured on day 1(one) of their 1st visit forall the groups and also were on day 60 in deficient group. Data were compared among the different groups, also in supplemented group just before and after supplementation. Analysis of data was done by appropriate statistical method. Mean blood Hb%, TC of RBC and PCV were significantly lower but reticulocyte count and serum bilirubin levels were significantly higher in patients suffering from hemolytic anemia due to G6PD deficiency in comparison to those of the healthy control. After supplementation with vitamin E (i.e. on day-60) Hb concentration, total count of RBC, PCV were significantly increased whereas, reticulocyte count and serum bilirubin levels were significantly decreased towards those of healthy control in supplemented group of patients in comparison to those of their pre-supplemented (day-1) and non-supplemented groups both on day-1 and day-60. Therefore, from this study it may be concluded that, deterioration of some of the hematological parameters occur in G6PD deficient hemolytic anemic patients, improvement of which occur following vitamin E supplementation, which clearly indicates the role of this antioxidant vitamin in reducing the rate of hemolysis in this group of patients. So, vitamin E supplementation can be considered along with other drugs to treat this group of patients. DOI: 10.3329/bjpp.v22i1.3563 Bangladesh J Physiol Pharmacol 2006; 22(1/2) : 12-17

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