Screening of glucose-6-phosphate dehydrogenase (G6PD) deficiency in two high endemic malaria populations, West Papua province and North Moluccas

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. This study aimed to characterize the G6PD gene variant distribution in Shenzhen of Guangdong province. Methods: A total of 33,562 individuals were selected at the hospital for retrospective analysis, of which 1,213 cases with enzymatic activity-confirmed G6PD deficiency were screened for G6PD gene variants. Amplification refractory mutation system PCR was first used to screen the 6 dominant mutants in the Chinese population (c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.392G>T, and c.871G>A). If the 6 hotspot variants were not found, next-generation sequencing was then performed. Finally, Sanger sequencing was used to verify all the mutations. Results: The incidence of G6PD deficiency in this study was 3.54%. A total of 26 kinds of mutants were found in the coding region, except for c.-8-624T>C, which was in the noncoding region. c.1376G>T and c.1388G>A, both located in exon 12, were the top 2 mutants, accounting for 68.43% of all individuals. The 6 hotspot mutations had a cumulative proportion of 94.02%. Conclusions: This study provided detailed characteristics of G6PD gene variants in Shenzhen, and the results would be valuable to enrich the knowledge of G6PD deficiency.

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Molecular Epidemiology of G6PD Genotypes in Different Ethnic Groups Residing in Saharan and Sahelian Zones of Mauritania

Pathogens ◽

10.3390/pathogens10080931 ◽

2021 ◽

Vol 10 (8) ◽

pp. 931

Author(s):

Oum Kelthoum Mamadou Djigo ◽

Mohamed Salem Ould Ahmedou Salem ◽

Sileye Mamadou Diallo ◽

Mohamed Abdallahi Bollahi ◽

Boushab Mohamed Boushab ◽

...

Keyword(s):

G6pd Deficiency ◽

African Ancestry ◽

Population Based ◽

Black African ◽

Plasmodium Vivax Malaria ◽

The Mediterranean ◽

Linguistic Groups ◽

Study Sites ◽

Glucose 6 Phosphate Dehydrogenase ◽

Genotype Screening

Plasmodium vivax malaria is endemic in Mauritania. Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may develop acute hemolytic anemia when exposed to 8-aminoquinoline antimalarial drugs, which are indispensable for a complete cure. The prevalence of G6PD allelic variants was assessed in different ethno-linguistic groups present in Mauritania. A total of 996 blood samples (447 males and 549 females; 499 white Moors and 497 individuals of black African ancestry) were collected from febrile patients in 6 different study sites: Aleg, Atar, Kiffa, Kobeni, Nouakchott, and Rosso. The presence of the African-type G6PD A- (G202A, A376G, A542T, G680T, and T968C mutations) and the Mediterranean-type G6PD B- (C563T) variants was assessed by PCR followed by restriction fragment length polymorphism and/or DNA sequencing. The prevalence of African-type G6PD A- genotype was 3.6% (36/996), with 6.3% (28/447) of hemizygote (A-) males and 1.5% (8/549) of homozygous (A-A-) females. Forty of 549 (7.3%) women were heterozygous (AA-). The following genotypes were observed among hemizygous men and/or homozygous women: A376G/G202A (22/996; 2.2%), A376G/T968C Betica-Selma (12/996; 1.2%), and A376G/A542T Santamaria (2/996; 0.2%). The Mediterranean-type G6PD B- genotype was not observed. The prevalence rates of G6PD A- genotype in male (10/243; 4.1%) and heterozygous female (6/256; 2.3%) white Moors were lower (p < 0.05) than those of males (18/204; 8.8%) and heterozygous females (34/293; 11.6%) of black African ancestry. There were only a few homozygous women among both white Moors (3/256; 1.2%) and those of black African ancestry (5/293; 1.7%). The prevalence of G6PD deficiency in Mauritania was comparable to that of neighboring countries in the Maghreb. Because of the purportedly close ethnic ties between the Mauritanian white Moors and the peoples in the Maghreb, further investigations on the possible existence of the Mediterranean-type allele are required. Moreover, a surveillance system of G6PD phenotype and/or genotype screening is warranted to establish and monitor a population-based prevalence of G6PD deficiency.

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Molecular basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency in three Taiwan aboriginal tribes

Human Genetics ◽

10.1007/bf00209477 ◽

1995 ◽

Vol 95 (6) ◽

Cited By ~ 7

Author(s):

TangK. Tang ◽

Wen-Yi Huang ◽

Chieh-Ju Chang Tang ◽

Mutsu Hsu ◽

Tai-Ann Cheng ◽

...

Keyword(s):

G6pd Deficiency ◽

Molecular Basis ◽

Glucose 6 Phosphate Dehydrogenase

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Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency and senile cataract in a Sardinian male population, Italy

Ophthalmic Epidemiology ◽

10.3109/09286580903312293 ◽

2009 ◽

Vol 16 (6) ◽

pp. 395-399 ◽

Cited By ~ 2

Author(s):

Antonio Pinna ◽

Adele Pes ◽

Angelo Zinellu ◽

Arturo Carta ◽

Giuliana Solinas

Keyword(s):

G6pd Deficiency ◽

Senile Cataract ◽

Male Population ◽

Glucose 6 Phosphate Dehydrogenase

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Glucose 6 phosphate dehydrogenase deficiency and hemoglobinopathy in South Western Region Nepal: a boon or burden

BMC Research Notes ◽

10.1186/s13104-019-4762-6 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Narayan Gautam ◽

Bhagwati Gaire ◽

Trishna Manandhar ◽

Bishnu P. Marasini ◽

Niranjan Parajuli ◽

...

Keyword(s):

Sickle Cell ◽

G6pd Deficiency ◽

Sickle Cell Trait ◽

Amplification Refractory Mutation System ◽

Cellulose Acetate Electrophoresis ◽

Positive Trait ◽

Arms Pcr ◽

Phenotypic Method ◽

Mutation System ◽

Glucose 6 Phosphate Dehydrogenase

Abstract Objectives The study was carried out to optimize the phenotypic method to characterize the sickle cell trait (SCT), sickle cell anemia (SCA), and β-thalassemia (β-TT) suspected sample from tharu community of South Western province-5, Nepal. SCT and SCA were further evaluated by genotypic method employing amplification refractory mutation system (ARMS PCR). Moreover, Glucose 6 phosphate dehydrogenase (G6PD) was estimated in those hemoglobinopathy to observe its prevalence. The accurate and reliable method can play an important role in reduction of morbidity and mortality rate. Results The 100 suspected cases were subjected to phenotypic method adopting cellulose acetate electrophoresis and genotypic method using ARMS PCR which portraits (5%) SCA positive test showing HBS/HBS, (38%) SCT positive trait HBA/HBS and (36%) cases normal HBA/HBA. β-TT (21%) cases were confirmed by electropherogram. G6PD deficiency was observed in (40%) of SCA, (18.4%) of SCT, (4.8%) of β-TT and (2.8%) in normal cases. Increased G6PD were developed only in SCT (5.3%) and β-TT (4.8%). The study highlighted sickle cell disorder (SCD) and β-TT as the most common hemoglobinopathy coexisting with G6PD deficiency. Though hemoglobinopathy sometime could be protective in malaria but G6PD deficiency can cause massive hemolysis which may exacerbate the condition.

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From Prejudice to Evidence: The Case of Rhizoma Coptidis in Singapore

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/871720 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Chin Ee Ho ◽

You Li Goh ◽

Chang Zhang

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

G6pd Deficiency ◽

Neonatal Jaundice ◽

Therapeutic Effects ◽

Evidence Based ◽

Rhizoma Coptidis ◽

History Of ◽

Hepatoprotective Effects ◽

Glucose 6 Phosphate Dehydrogenase

Rhizoma Coptidis (RC), commonly known ashuanglian, is a herb frequently used in Traditional Chinese Medicine (TCM) prescriptions. Known to have “clearing damp-heat, quenching fire and counteracting poison” properties, it was widely used in the Chinese community in Singapore. Berberine, an alkaloid isolated from RC, is known to have a wide array of therapeutic effects including antimicrobial, antineoplastic, and hepatoprotective effects. In 1978, RC was implicated in causing neonatal jaundice (NNJ) and kernicterus in neonates suffering from glucose-6-phosphate dehydrogenase (G6PD) deficiency, leading to the banning of RC and berberine in Singapore. More than three decades later, accumulating evidence-based studies pointing to the safety of RC for general public and better understanding of G6PD deficiency, the Health Sciences Authority (HSA) in Singapore reviewed and lifted the prohibition on RC and berberine, turning a brand new chapter in the history of TCM in Singapore. This paper aims to review the safety of RC and berberine, using the prohibition of use and subsequent lifting of ban on RC and berberine in Singapore as an illustration to highlight the importance of evidence-based studies in Traditional Chinese Medicine (TCM).

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A Rare Case of Coexistence of Homozygous β-Thalassaemia and Glucose 6 Phosphate Dehydrogenase Deficiency

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2020/44968.14085 ◽

2020 ◽

Author(s):

Jitendar Mohan Khunger ◽

Monika Gupta ◽

Ankur Jain ◽

Monica Khunger Malhotra

Keyword(s):

Oxidative Stress ◽

Blood Cells ◽

G6pd Deficiency ◽

Rare Case ◽

Dehydrogenase Deficiency ◽

Globin Gene ◽

Genetic Abnormality ◽

Wide Range ◽

Symptomatic Anaemia ◽

Glucose 6 Phosphate Dehydrogenase

β-thalassaemia is one of the most prevalent autosomal disorders worldwide. Mutations/deletions in globin gene underlie deficiencies in Haemoglobin (Hb) production, which can interfere with oxygen delivery by Hb, resulting in thalassaemias causing anaemias with a wide range of disease severity. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is a genetic abnormality resulting in inadequate amount of G6PD in the Red Blood Cells (RBCs). In patients with G6PD deficiency, the reduced or absent activity of the enzyme in RBCs causes premature haemolysis and symptomatic anaemia. The marked oxidative stress caused by homozygous β-thalassaemia is apparently incompatible with G6PD deficiency. Here, a rare case of six-month-old male child is described who presented with severe pallor hepato-splenomegaly and these two conditions co-existed in this patient.

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The impact of using primaquine without prior G6PD testing: a case series describing the obstacles to the medical management of haemolysis

Wellcome Open Research ◽

10.12688/wellcomeopenres.15100.2 ◽

2019 ◽

Vol 4 ◽

pp. 25 ◽

Cited By ~ 2

Author(s):

Cindy S. Chu ◽

Germana Bancone ◽

Nay Lin Soe ◽

Verena I. Carrara ◽

Gornpan Gornsawun ◽

...

Keyword(s):

Health Care Providers ◽

G6pd Deficiency ◽

Case Series ◽

Radical Cure ◽

Care Providers ◽

Medical Treatments ◽

Normal Individuals ◽

High Index Of Suspicion ◽

Glucose 6 Phosphate Dehydrogenase ◽

The Impact

Radical cure of Plasmodium vivax malaria in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals employs weekly primaquine dosing. This is the only recommended regimen for this patient sub-group. If national malaria programs mandate daily primaquine dosing (the recommended regimen for G6PD normal individuals), then G6PD testing before prescription is necessary to avoid iatrogenic haemolysis in G6PD deficient individuals. In this case series, two P. vivax infected patients with unknown G6PD status from two different countries were prescribed primaquine as per national malaria program guidelines. During treatment both patients presented to the clinic with symptoms of anaemia after taking primaquine incorrectly. The clinical management of the iatrogenic severe haemolysis that occurred in these patients demonstrates the various adverse effects primaquine can cause, that other common medical treatments also have haemolytic potential, and how the diagnosis of G6PD deficiency can be elusive during acute haemolysis. Health care providers should provide careful instructions about primaquine dosing, be watchful for haemolysis, and have a high index of suspicion for G6PD deficiency in the presence of haemolysis if the G6PD status is previously unknown.

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Protective effect of Mediterranean-type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria

eLife ◽

10.7554/elife.62448 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ghulam R Awab ◽

Fahima Aaram ◽

Natsuda Jamornthanyawat ◽

Kanokon Suwannasin ◽

Watcharee Pagornrat ◽

...

Keyword(s):

Protective Effect ◽

Plasmodium Vivax ◽

G6pd Deficiency ◽

Vivax Malaria ◽

Malaria Incidence ◽

Large Population ◽

Credible Interval ◽

Radical Cure ◽

Plasmodium Vivax Malaria ◽

Glucose 6 Phosphate Dehydrogenase

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with reductions in symptomatic P. vivax malaria incidence of 76% (95% credible interval [CI], 58–88) in hemizygous males and homozygous females combined and 55% (95% CI, 38–68) in heterozygous females. Unless there is very large population stratification within the Pashtun (confounding these results), the G6PD Med genotype confers a very large and gene-dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by studies measuring G6PD deficiency prevalence in healthy subjects.

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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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