ESSENTIALS OF DIAGNOSIS
X-linked recessive disorder seen commonly in American Black men.
Episodic hemolysis in response to oxidant drugs or infection.
Bite cells and blister cells on the peripheral blood smear.
Reduced levels of glucose-6-phosphate dehydrogenase between hemolytic episodes.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a hereditary enzyme defect that causes episodic hemolytic anemia because of the decreased ability of RBCs to deal with oxidative stresses. G6PD deficiency leads to excess oxidized glutathione that forces hemoglobin to denature and form precipitants called Heinz bodies. Heinz bodies cause RBC membrane damage, which leads to premature removal of these RBCs 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 RBC 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 CAD, and possibly have fewer cancers and greater longevity.
G6PD deficiency is an X-linked disorder affecting 10–15% of American hemizygous Black males and rare female homozygotes. Female carriers are rarely affected—only when an unusually high percentage of cells producing the normal enzyme are X-inactivated.
Patients are usually healthy, without chronic hemolytic anemia or splenomegaly. Hemolysis occurs episodically due to oxidative stress on the RBCs, 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, pegloticase, 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 RBCs (with low enzyme activity) are removed and replaced with a population of young RBCs (reticulocytes) with adequate functional levels of G6PD. Severe G6PD deficiency (as in ...