Glucose-6-phosphate dehydrogenase deficiency

• Published in: Blood 2020-09, Vol.136 (11), p.1225-1240
• Main Authors: Luzzatto, Lucio, Ally, Mwashungi, Notaro, Rosario
• Format: Article
• Language: English
• Subjects: Blood Donors; Blood Safety; Glucosephosphate Dehydrogenase - genetics; Glucosephosphate Dehydrogenase Deficiency - epidemiology; Glucosephosphate Dehydrogenase Deficiency - genetics; HIV Infections; Humans; Primaquine - therapeutic use
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2019000944

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is 1 of the commonest human enzymopathies, caused by 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: approximately 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 triggered by ingestion of fava beans, by any of a number of drugs (for example, primaquine, rasburicase), or, more rarely, by infection. Approximately one-half of the G6PD mutations are instead sporadic: rare patients with these mutations present with chronic nonspherocytic hemolytic anemia. Almost all G6PD mutations are missense mutations, causing amino acid replacements that entail deficiency of G6PD enzyme activity: they compromise the stability of the protein, the catalytic activity is decreased, or a combination of both mechanisms occurs. 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 recently introduced analog tafenoquine are required for the elimination of malaria. [Display omitted]