Glucose 6-phosphate dehydrogenase (G6PD) deficiency is one of the commonest human enzymopathies: it is due to 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: about 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 this is triggered by ingestion of fava beans, or by any of a number of drugs (e.g. primaquine, rasburicase), or more rarely by infection. About one-half of the G6PD mutations are instead sporadic: rare patients with these mutations present with chronic non-spherocytic hemolytic anemia. Almost all G6PD mutations are missense mutations, causing amino acid replacements that entail deficiency of G6PD enzyme activity because they compromise the stability of the protein, or because the catalytic activity is decreased, or through a combination of both mechanisms: 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 analogue tafenoquine, recently introduced, are required for the elimination of malaria.
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