Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a hereditary enzyme defect that causes episodic hemolytic anemia because of the decreased ability of red blood cells to deal with oxidative stresses. G6PD deficiency leads to excess oxidized glutathione (hence, inadequate levels of reduced glutathione) that forces hemoglobin to denature and form precipitants called Heinz bodies. Heinz bodies cause red blood cell membrane damage, which leads to premature removal of these red blood cells by reticuloendothelial cells within the spleen (ie, extravascular hemolysis).
Numerous G6PD isoenzymes have been described. The usual isoenzyme found in American blacks is designated G6PD-A and that found in whites is designated G6PD-B, both of which have normal function and stability and therefore no hemolytic anemia. Ten to 15 percent of American blacks have the variant G6PD isoenzyme designated A–, in which there is both a reduction in normal enzyme activity and a reduction in its stability. The A– isoenzyme activity declines rapidly as the red blood cell ages past 40 days, a fact that explains the clinical findings in this disorder. More than 150 G6PD isoenzyme variants have been described, including some Mediterranean, Ashkenazi Jewish, and Asian variants with very low enzyme activity, episodic hemolysis, and exacerbations due to oxidizing substances including fava beans(class II G6PD activity). The other classes of G6PD isoenzyme activity are class I, extremely low activity with associated chronic, severe hemolysis; class III, 10–60% activity with episodic hemolysis (includes the American black A– isoform); class IV, 60–150% activity (normal); and class V, greater than 150% activity. Patients with G6PD deficiency seem to be protected from malaria parasitic infection, have less coronary artery disease, and possibly have fewer cancers and greater longevity.