Practical approach for characterization of glucose 6‐phosphate dehydrogenase (G6PD) deficiency in countries with population ethnically heterogeneous: Description of seven new G6PD mutants

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

doi:10.1002/ajh.22218

Cited by 7 publications

(7 citation statements)

References 10 publications

(1 reference statement)

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“…In the present study, a 41.0% prevalence of G6PD deficiency was recorded among the study population which is higher than the suggested Ghana’s 15–26% prevalence by the World Health Organization [ 25 ] or the estimated 1.2–30.7% prevalence in Africa [ 26 ]. This results is also at variance with a previous cross-sectional study undertaken in the Brong-Ahafo region of Ghana which recorded 32% G6PD enzymopathy prevalence among blood donors [ 27 ].…”

Section: Discussioncontrasting

confidence: 62%

Significantly elevated foetal haemoglobin levels in individuals with glucose 6-phosphate dehydrogenase disease and/or sickle cell trait: a cross-sectional study in Cape Coast, Ghana

et al. 2017

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BackgroundPreviously published data have demonstrated that sickle red blood cells produce twice as much reactive oxygen species (ROS) suggesting that co-inheritance of sickle cell disease (SCD) and glucose 6-phosphate dehydrogenase (G6PD) enzymopathy could lead to more severe anaemia during sickling crises. Elevated foetal haemoglobin (Hb F) levels have been shown to have positive modulatory effects on sickling crises and disease outcomes. This study sought to assess how inheritance of G6PD enzymopathy affects the level of Hb F and haemoglobin concentration in adults in steady state.MethodsThis cross-sectional study selected 100 out-patients (41 males and 59 females) visiting the University of Cape Coast hospital, between January, 2016 and May, 2016. Cellulose acetate electrophoresis (pH 8.2–8.6), methaemoglobin reductase test, modified Betke alkaline denaturation methods were used to investigate haemoglobin variants, qualitative G6PD status, and %Hb F levels in venous blood samples drawn from these participants. Data was analysed with GraphPad Prism 6 and SPSS and significance set at p < 0.05.ResultsForty one percent of the participants demonstrated qualitative G6PD enzymopathy whereas only 10% demonstrated Hb AS type (Sickle cell trait, SCT). 5% of the participants co-inherited SCT and G6PD enzymopathy. %Hb F levels in G6PD deficient males was significantly higher than in G6PD deficient females [(p = 0.0003, 2.696% (males) vs 1.975% (females)], although the %Hb F levels was comparable in non-G6PD deficient individuals. %Hb F levels were significantly elevated in males with SCT only (p < 0.05), or G6PD enzymopathy only (p < 0.0001), or SCT + G6PD enzymopathy (p < 0.0001) compared to males with none of these pathologies even though their respective haemoglobin levels were comparable. Male participants with G6PD enzymopathy + SCT co-inheritance had significantly elevated %Hb F when compared to their counterparts with only G6PD enzymopathy (p < 0.001). Male gender [(p = 0.001, OR: 6.912 (2.277–20.984)] partial defective G6PD enzyme [(p = 0.00, OR: 7.567E8 (8.443E7–6.782E9)] SCT [(p = 0.026, OR: 4.625 (1.196–17.881)] were factors associated with raised %Hb F levels ≥2.5.ConclusionThe inheritance of G6PD defect and/or SCT significantly elevate %Hb F levels in the steady state even though haemoglobin levels are not affected.

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Section: Discussioncontrasting

confidence: 62%

Significantly elevated foetal haemoglobin levels in individuals with glucose 6-phosphate dehydrogenase disease and/or sickle cell trait: a cross-sectional study in Cape Coast, Ghana

et al. 2017

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“…One asymptomatic male with extremely reduced activity of glucose-6-phosphate dehydrogenase had the G6PD p.R166C variant located in the X chromosome. This variant was described in 2012 [13] (Table 3).…”

Section: Sanger Sequencingmentioning

confidence: 96%

Targeted next-generation sequencing identified novel mutations associated with hereditary anemias in Brazil

et al. 2020

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Hereditary anemias are a group of heterogeneous disorders including hemolytic anemias and hyporegenerative anemias, as congenital dyserythropoietic anemia (CDA). Causative mutations occur in a wide range of genes leading to deficiencies in red cell production, structure, or function. The genetic screening of the main genes is important for timely diagnosis, since routine laboratory tests fail in a percentage of the cases, appropriate treatment decisions, and genetic counseling purposes. A conventional gene-by-gene sequencing approach is expensive and highly time-consuming, due to the genetic complexity of these diseases. To overcome this problem, we customized a targeted sequencing panel covering 35 genes previously associated to red cell disorders. We analyzed 36 patients, and potentially pathogenic variants were identified in 26 cases (72%). Twenty variants were novel. Remarkably, mutations in the SPTB gene (βspectrin) were found in 34.6% of the patients with hereditary spherocytosis (HS), suggesting that SPTB is a major HS gene in the Southeast of Brazil. We also identified two cases with dominant HS presenting null mutations in trans with α-LELY in SPTA1 gene. This is the first comprehensive genetic analysis for hereditary anemias in the Brazilian population, contributing to a better understanding of the genetic basis and phenotypic consequences of these rare conditions in our population.

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“…Genetic analyses revealed the presence of a Toledo-type G6PD mutation (496C>T resulting in Arg166>Cys substitution) in all 3 patients and the mother. 11…”

Section: Patient Historymentioning

confidence: 99%

Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis

Siler

Romão

Tejera

et al. 2017

Journal of Allergy and Clinical Immunology

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Because severe G6PD deficiency can be a phenocopy of chronic granulomatous disease with regard to the cellular and clinical phenotype, careful evaluation of neutrophil function seems mandatory in these patients to decide on appropriate anti-infective preventive measures. Determining the level of G6PD enzyme activity should be followed by analysis of reactive oxygen species production and NET formation to decide on required antibiotic and antimycotic prophylaxis.

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Practical approach for characterization of glucose 6‐phosphate dehydrogenase (G6PD) deficiency in countries with population ethnically heterogeneous: Description of seven new G6PD mutants

Cited by 7 publications

References 10 publications

Significantly elevated foetal haemoglobin levels in individuals with glucose 6-phosphate dehydrogenase disease and/or sickle cell trait: a cross-sectional study in Cape Coast, Ghana

Significantly elevated foetal haemoglobin levels in individuals with glucose 6-phosphate dehydrogenase disease and/or sickle cell trait: a cross-sectional study in Cape Coast, Ghana

Targeted next-generation sequencing identified novel mutations associated with hereditary anemias in Brazil

Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis

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