Addressing the gender-knowledge gap in glucose-6-phosphate dehydrogenase deficiency: challenges and opportunities

Gonzalo J Domingo, Nicole Advani, Ari W Satyagraha, Carol H Sibley, Elizabeth Rowley, Michael Kalnoky, Jessica Cohen, Michael Parker, Maureen Kelley, Gonzalo J Domingo, Nicole Advani, Ari W Satyagraha, Carol H Sibley, Elizabeth Rowley, Michael Kalnoky, Jessica Cohen, Michael Parker, Maureen Kelley

Abstract

Glucose-6-phosphate dehyrdgoenase (G6PD) deficiency is a common X-linked genetic trait, with an associated enzyme phenotype, whereby males are either G6PD deficient or normal, but females exhibit a broader range of G6PD deficiencies, ranging from severe deficiency to normal. Heterozygous females typically have intermediate G6PD activity. G6PD deficiency has implications for the safe treatment for Plasmodium vivax malaria. Individuals with this deficiency are at greater risk of serious adverse events following treatment with the only curative class of anti-malarials, 8-aminoquinolines, such as primaquine. Quantitative diagnostic tests for G6PD deficiency are complex and require sophisticated laboratories. The commonly used qualitative tests, do not discriminate intermediate G6PD activities. This has resulted in poor understanding of the epidemiology of G6PD activity in females and its corresponding treatment ramifications. New simple-to-use quantitative tests, and a momentum to eliminate malaria, create an opportunity to address this knowledge gap. While this will require additional resources for clinical studies, adequate operational research, and appropriate pharmacovigilance, the health benefits from this investment go beyond the immediate intervention for which the G6PD status is first diagnosed.

Figures

Figure 1.
Figure 1.
Association between G6PD genotype in males and females, and red blood cell G6PD activity levels in a population. Histograms show the distributions of hemoglobin-normalized G6PD activity levels for (A) males and (B) females.
Figure 2.
Figure 2.
Population distribution for males and females arranged by individual G6PD activity level (U/g Hb) at different G6PD-deficient allele frequencies in males. The distributions were modeled based on the Hardy–Weinberg equilibrium and using empirical data from a cross-sectional G6PD study, whereby G6PD activity was measured by the Trinity quantitative test (G-6-PDH 35-A). Population distributions are shown for (A) males and (B) females. These distributions were used for Table 2.

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