Deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD) results in an inability of red cells to combat the production of the toxic substances superoxide (O2-) and hydrogen peroxide (H2O2). As both superoxide and hydrogen peroxide are toxic to the cells, their accumulation results in cellular damage with resultant hemolysis. Normally, oxygen is transported unchanged by red cells; however, the above-mentioned toxic radicals may be produced. There are several enzyme systems for neutralizing superoxide and hydrogen peroxide to include superoxide dismutase, catalase and the glutathione-requiring system. The glutathione system neutralizes hydrogen peroxide and requires a continuous supply of NADPH, which is provided by the hexosemonophosphate shunt. When the enzyme glucose-6-phosphate dehydrogenase is deficient, the hexosemonophosphate shunt is impaired resulting in a deficiency of NADPH, which then results in an inability to convert hydrogen peroxide into water. As the hydrogen peroxide accumulates it causes damage to the red blood cell. Clinically, this results in hemolysis and depending on the severity of disease, possible anemia.

Hemolysis may be induced in patients with G6PD deficiency by various stressors. The most common stressors are infections and oxidant drugs. When patients are exposed, intravascular hemolysis results and is manifested by anemia, indirect hyperbilirubinemia, an elevated LDH, and reticulocytosis. Intravascular hemolysis may be detected by the presence of hemoglobinuria, hemoglobinemia and hemosiderinuria. Extravascular hemolysis of red cells also occurs secondary to the presence of precipitates of denatured hemoglobin within the red cells. These patients also display a tendency toward gallstone formation. The severity of the symptoms of this disease is variable depending on the severity of the enzyme deficiency and the type of enzyme present.

There are more than 100 different forms of this enzyme. The B form (found in normal whites and in most blacks) and the A form (found in 30 percent of normal black men and 55 percent of normal black women) are easily detected by electrophoresis and are not associated with pathology. The other forms of this enzyme have been isolated from patients who are deficient in this enzyme. The stability of the various isoenzymes is variable and results in differing levels of disease severity based on the type of enzyme present and the level of deficiency.

Blacks are often afflicted by G6PD type A- form that is characterized by decreasing levels of the enzyme in red blood cells over time. In essence, the older the red cell is, the less enzyme it has until old cells are completely deficient whereas newer cells may have near normal levels. Approximately 20% of black females carry the gene and 10% of black males are afflicted. A more severe form of this disease occurs in persons of Mediterranean decent (Italians, Greeks, Sicilians, and persons from the island of Sardinia) and persons from the Near East and North Africa. The G6PD type BMediterranean form results in a severe deficiency in all cells including those newly released from the marrow. Therefore, when hemolysis occurs, it is severe and life-threatening.

The diagnosis is established by measuring the level of the enzyme G6PD in red cells. In patients with G6PD type A- form the enzyme levels may be normal if measured directly following a hemolytic event but will be depressed if rechecked when the patient is symptom free. The reason for this is that after a hemolytic event in these patients, the older, enzyme-deficient cells have been destroyed via hemolysis and are not included in the measurement whereas the remaining newer cells still have near normal levels of the enzyme. Heinz bodies are intracellular precipitates of denatured hemoglobin which are visible when the cells are stained with crystal violet. The presence of Heinz bodies in a patient with hemolytic anemia should suggest the diagnosis of G6PD deficiency.

Avoidance of known stressors is the best management methd for this genetic disease. As stated, oxidant drugs, infections, and fava beans are known stressors. In the case of acute, severe hemolytic episodes, fluid support and transfusion therapy may be required.