GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
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 (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. Patients with G6PD deficiency seem
Symptoms and Signs
Patients are usually healthy, without chronic hemolytic anemia or splenomegaly. Hemolysis occurs episodically as a result of oxidative stress on the red blood cells, generated either by infection or exposure to certain medications. Medications initiating hemolysis that should be avoided include dapsone, methylene blue, phenazopyridine, primaquine, rasburicase, toluidine blue, nitrofurantoin, trimethoprim/sulfamethoxazole, sulfadiazine, and quinolones. Other medications, such as chloroquine, quinine, high-dose aspirin, and isoniazid, have been implicated but are less certain as offenders since they are often given during infections. Even with continuous use of the offending medication, the hemolytic episode is self-limited because older red blood cells (with low enzyme activity) are removed and replaced with a population of young red blood cells (reticulocytes) with adequate functional levels of G6PD. Severe G6PD deficiency (as in Mediterranean variants) may produce a chronic hemolytic anemia.
No treatment is necessary except to avoid known oxidant medications.