Glucose‐6‐phosphate Dehydrogenase (G6PD) Deficiency: Genetics

Abstract

AbstractDeficiency ofglucose‐6‐phosphate dehydrogenase(G6PD) is the most common enzyme deficiency in humans and is due to many different local variants with point mutations in the X‐linked G6PD gene. In populations that have a history of malaria infection G6PD alleles causing deficiency can reach frequencies of 10% or more. Though often asymptomatic, the enzyme deficiency can lead to acute haemolytic anaemia caused by failure to maintain sufficiently high levels of nicotinamide–adenine dinucleotide phosphate reduced form (NADPH) to prevent oxidative damage in red cells. Rare sporadic variants that can occur in all human populations can cause more severe chronic haemolytic anaemia. G6PD deficiency is also one of the major causes of neonatal jaundice. The prevalence of G6PD‐deficient alleles is likely due to the fact that they confer a selective advantage against malaria infection.Key Concepts:G6PD deficiency is widespread because deficient individuals have a selective advantage against malaria infection.G6PD in red cells maintains the levels of NADPH, essential for reducing oxidising agents.Deficient variants cannot maintain high NADPH levels and reactive oxygen species cause haemolysis.Deficient variants can reach polymorphic levels and different populations have different variants.This pattern of variation arose recently, coincident with the spread of malaria in human populations.Most deficient variants are unstablein vivoand therefore cause very low levels in red cells, where the enzyme is not turned over.Knowledge of the G6PD variants in a population can be useful in limiting illness caused by G6PD deficiency.