Glucose-6-Phosphate Dehydrogenase Deficiency

Key Features

• Hereditary enzyme defect causes episodic hemolytic anemia from decreased ability of red blood cells (RBCs) to deal with oxidative stresses

• 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 (extravascular hemolysis)

• 10–15% 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 stability and therefore no hemolytic anemia

• A– isoenzyme activity declines rapidly as the RBC ages past 40 days, a fact that explains the clinical findings in this disorder

• Mediterranean, Ashkenazi Jewish, and Asian variants have very low enzyme activity (class II G6PD activity)

• Other classes of G6PD isoenzyme activity

  • Class I: low activity, with chronic, severe hemolysis

  • Class III: 10–60% activity with episodic hemolysis

  • Class IV: 60–150% activity (normal)

  • Class V: > 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

Clinical Findings

• Usually healthy, without chronic hemolytic anemia or splenomegaly

• Hemolysis occurs at time of infection or exposure to certain drugs

• Common drugs initiating hemolysis

  • Dapsone

  • Methylene blue

  • Phenazopyridine

  • Primaquine

  • Rasburicase

  • Toluidine blue

  • Nitrofurantoin

  • Trimethoprim/sulfamethoxazole

  • Sulfadiazine

  • Pegloticase

  • Quinolones

• Hemolytic episode self-limited, even with continued use of offending drug, because older RBCs (with low G6PD activity) are removed and replaced with young RBCs (with adequate G6PD activity)

• Chronic hemolytic anemia in severe G6PD deficiency (eg, Mediterranean variants)

Diagnosis

• Blood is normal between hemolytic episodes

• Hemoglobin rarely falls below 8 g/dL, though reticulocytosis and increased indirect bilirubin occur during hemolytic episodes

• G6PD enzyme assays are low, especially in severe cases of G6PD deficiency

• G6PD enzyme assays may be falsely normal if performed during or shortly after hemolytic episode during the period of reticulocytosis

• Peripheral blood cell smear, although not diagnostic, may reveal bite cells and blister cells

• Heinz bodies may be seen on peripheral blood smear stained with cresyl violet

Treatment

• Avoid known oxidant drugs

• Otherwise, no treatment necessary