Glucose-6-phosphate dehydrogenase deficiency

Abstract Glucose 6-phosphate dehydrogenase (G6PD) deficiency is 1 of the commonest human enzymopathies, caused by inherited mutations of the X-linked gene G6PD. G6PD deficiency makes red cells highly vulnerable to oxidative damage, and therefore susceptible to hemolysis. Over 200 G6PD mutations are known: approximately one-half are polymorphic and therefore common in various populations. Some 500 million persons with any of these mutations are mostly asymptomatic throughout their lifetime; however, any of them may develop acute and sometimes very severe hemolytic anemia when triggered by ingestion of fava beans, by any of a number of drugs (for example, primaquine, rasburicase), or, more rarely, by infection. Approximately one-half of the G6PD mutations are instead sporadic: rare patients with these mutations present with chronic nonspherocytic hemolytic anemia. Almost all G6PD mutations are missense mutations, causing amino acid replacements that entail deficiency of G6PD enzyme activity: they compromise the stability of the protein, the catalytic activity is decreased, or a combination of both mechanisms occurs. Thus, genotype-phenotype correlations have been reasonably well clarified in many cases. G6PD deficiency correlates remarkably, in its geographic distribution, with past/present malaria endemicity: indeed, it is a unique example of an X-linked human polymorphism balanced through protection of heterozygotes from malaria mortality. Acute hemolytic anemia can be managed effectively provided it is promptly diagnosed. Reliable diagnostic procedures are available, with point-of-care tests becoming increasingly important where primaquine and its recently introduced analog tafenoquine are required for the elimination of malaria.

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G6PD Variants and Haemolytic Sensitivity to Primaquine and Other Drugs

Frontiers in Pharmacology ◽

10.3389/fphar.2021.638885 ◽

2021 ◽

Vol 12 ◽

Author(s):

Germana Bancone ◽

Cindy S. Chu

Keyword(s):

G6pd Deficiency ◽

Point Of Care ◽

Fifth Century ◽

Laboratory Research ◽

Detailed Knowledge ◽

Drug Induced ◽

Phenotypic Characterisation ◽

Glucose 6 Phosphate Dehydrogenase ◽

Point Of Care Tests

Restrictions on the cultivation and ingestion of fava beans were first reported as early as the fifth century BC. Not until the late 19th century were clinical descriptions of fava-induced disease reported and soon after characterised as “favism” in the early 20th century. It is now well known that favism as well as drug-induced haemolysis is caused by a deficiency of the glucose-6-phosphate dehydrogenase (G6PD) enzyme, one of the most common enzyme deficiency in humans. Interest about the interaction between G6PD deficiency and therapeutics has increased recently because mass treatment with oxidative 8-aminoquinolines is necessary for malaria elimination. Historically, assessments of haemolytic risk have focused on the clinical outcomes (e.g., haemolysis) associated with either a simplified phenotypic G6PD characterisation (deficient or normal) or an ill-fitting classification of G6PD genetic variants. It is increasingly apparent that detailed knowledge of both aspects is required for a complete understanding of haemolytic risk. While more attention has been devoted recently to better phenotypic characterisation of G6PD activity (including the development of new point-of care tests), the classification of G6PD variants should be revised to be clinically useful in malaria eliminating countries and in populations with prevalent G6PD deficiency. The scope of this work is to summarize available literature on drug-induced haemolysis among individuals with different G6PD variants and to highlight knowledge gaps that could be filled with further clinical and laboratory research.

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

Blood ◽

10.1182/blood-2012-03-416032 ◽

2012 ◽

Vol 120 (20) ◽

pp. 4123-4133 ◽

Cited By ~ 60

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.

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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 ◽

10.1182/blood.v59.2.428.428 ◽

1982 ◽

Vol 59 (2) ◽

pp. 428-434 ◽

Cited By ~ 41

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.

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

Scientific Reports ◽

10.1038/s41598-020-74200-y ◽

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.

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

Human Genetics ◽

10.1007/bf00293894 ◽

1989 ◽

Vol 81 (2) ◽

pp. 161-164 ◽

Cited By ~ 8

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

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00600-16 ◽

2016 ◽

Vol 60 (10) ◽

pp. 5906-5913 ◽

Cited By ~ 5

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.

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

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-22.6.471 ◽

2017 ◽

Vol 22 (6) ◽

pp. 471-471 ◽

Cited By ~ 1

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.

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

Bangladesh Journal of Physiology and Pharmacology ◽

10.3329/bjpp.v22i1.3563 ◽

1970 ◽

pp. 12-17 ◽

Cited By ~ 1

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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Rapid quantitative assays for glucose-6-phosphate dehydrogenase (G6PD) and hemoglobin combined on a capillary-driven microfluidic chip

Lab on a Chip ◽

10.1039/d1lc00354b ◽

2021 ◽

Author(s):

Marco Rocca ◽

Yuksel Temiz ◽

Marie Laetitia Salva ◽

Samuel Castonguay ◽

Thomas Gervais ◽

...

Keyword(s):

Hemolytic Anemia ◽

Microfluidic Chip ◽

G6pd Deficiency ◽

Metabolic Disorder ◽

Rapid Tests ◽

Glucose 6 Phosphate Dehydrogenase

Rapid tests for glucose-6-phosphate dehydrogenase (G6PD) are extremely important for determining G6PD deficiency, a widespread metabolic disorder which triggers hemolytic anemia in response to primaquine and tafenoquine medication, the most...

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Investigation of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Prevalence in a Plasmodium vivax Endemic Area in the Republic of Korea (ROK)

10.21203/rs.3.rs-32936/v1 ◽

2020 ◽

Author(s):

Wonsig Lee ◽

Sang-Eun Lee ◽

Kyung Tae Noh

Keyword(s):

Hemolytic Anemia ◽

G6pd Deficiency ◽

Republic Of Korea ◽

Nucleotide Position ◽

Malaria Chemoprophylaxis ◽

The Republic ◽

Blood Specimens ◽

Glucose 6 Phosphate Dehydrogenase ◽

Distribution Testing ◽

Number Of Individuals

Abstract Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most prevalent inborn disorder. This X-chromosome-linked recessive disease affects more than 400 million people globally, and is associated with hemolytic anemia after medication with the anti-latent malaria drug, primaquine. To prevent malaria, the Republic of Korea (ROK) Army administers malaria chemoprophylaxis. Due to the previously low G6PD deficiency prevalence in the ROK, prior to primaquine distribution, testing for G6PD deficiency was not mandatory. Here, we investigate G6PD deficiency prevalence to evaluate the risk from malaria chemoprophylaxis.Methods: Blood specimens from 1,632 soldiers entering training camp for the 3rd Infantry of the ROK Army were collected. CareStart™ Biosensor for G6PD and Hemoglobin was used to detect G6PD levels. G6PD variants using the DiaPlexC G6PD Genotyping kit (Asian type) and full-length sequencing were examined.Results: Of 1,632 blood specimens tested, none were observed to be G6Pd deficient. The median value of all tested samples was 7.582 U/g Hb. An investigation of 170 G6PD DNA variants were analyzed and categorized as partially low (n=134, 30%–80% (2.27–6.05 U/g Hb) of the median value), high (n=3, >150% (>11.373 U/g Hb) of the median value), or normal (n=36, 4.6–13.5 U/g Hb), and none were amplified by the DiaPlexC kit. Five silent mutations (C→T) in 38 partially abnormal specimens were found at the 1311th nucleotide position by sequence analysis. Another 8 silent mutations (T93C) were also detected in 134 partially abnormal specimens. Thus, we inferred that these silent mutations could be related to G6PD deficiency.Conclusions: This G6PD deficiency prevalence study, conducted among participants from the 3rd Infantry of the ROK Army, provided crucial evidence for the safety of malaria chemoprophylaxis. Here, we found that the prevalence of G6PD deficiency among 1,632 young soldiers was nearly 0. Although G6PD phenotypic mutations were not detected, many silent mutations (C1311T and T93C) were observed. Thus, we inferred that malaria chemoprophylaxis is relatively safe against G6PD deficiency-mediated hemolytic anemia. However, given the number of individuals whose G6PD were at the low end of the normal range and the frequent detection of G6PD deficiency-related mutations, consistent monitoring of G6PD deficiency is needed.

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