IM Quiz: G6PD

The gene for G6PD is located on the X-chromosome; thus, G6PD deficiency is a sex-linked trait. Hemolytic anemia occurs much more commonly in males than in heterozygote female carriers, who usually are asymptomatic. Of the more than 100 variants of G6PD, the most commonly encountered variant of clinical significance in the United States is the A- type, which is found in about 15 percent of black males. It generally causes less severe hemolysis than the Mediterranean variant (sensitivity to fava beans).

Hemolysis usually is precipitated by an environment oxidant stress, most commonly viral or bacterial infection, through an unknown mechanism. Certain drugs, such as antimalarial agents (primaquine, pamaquine, dapsone), sulfonamides (sulfamethoxazole), phenacetin (Acetaminophen is a metabolite of phenacetin),and Vitamin K, also can trigger hemolysis. These oxidant stresses cause precipitation of hemoglobin because affected persons are unable to maintain adequate intracellular levels of reduced glutathione. Precipitated hemoglobin forms Heinz bodies that are visualized only with supravital stains not Wright stains; however, these are not usually seen after the first day or so, since these are readily removed by the spleen. Their removal leads to the formation of "bite cells", red cells which have lost a peripheral portion of the cell. Multiple bites can cause the formation of fragments and even spherocytes.

The diagnosis should be considered in any person experiencing a hemolytic episode. However, since decreased G6PD levels are found mainly in older cells, a false negative test may be obtained during a hemolytic crisis when there is a high proportion of young red blood cells. Thus one should repeat the test upon recovery.

The hemolysis is usually self-limited and no specific treatment is necessary. Unless a severe hemolytic episode with hemoglobinuria occurs, then maintaining adequate urine output is important.