Glucose-6-phosphate dehydrogenase deficiency

Summary

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. Because its gene locus is on the X- chromosome it is more common in males than females in all populations. Prevalence rates vary from 62% among Kurdish Jews to the very low rates (0.1% or less in Japan, for example), which are compatible with sporadic cases arising from spontaneous mutations. However, there is at least one population in which G6PD deficiency has not been found, namely the indigenous (Amerindian) population of America. Approximately 400 variants have been described. Despite the clinical burden imposed by this enzymopathy, polymorphic frequencies have been reached in many populations. There is abundant epidemiological evidence that this has hap- pened because of a biological advantage conferred on heterozygotes in falciparum malaria endemic areas. This advantage may apply to quartan malaria as well. Clinical severity varies, from the rare chronic non- spherocytic haemolytic anaemia to progressively milder forms like the Mediterranean and A — types. The other clinical syndromes, i.e. neonatal jaundice and haemolysis caused by infections, foods, drugs and chemicals, are not always predictable. This is because only a fraction of such enzymo-pathic persons develop these syndromes after exposure to the relevant stimulus. Modern techniques of molecular biology may elucidate why this is so. There is some emerging evidence that the genetic burden or survival value associated with G6PD deficiency may be relevant not only in tropical and infectious diseases, but also in their chemotherapy (e.g. malaria) as well as in the control of a long-recognized environmental pollutant such as lead.