Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic defect common in blacks that can result in hemolysis after acute illnesses or intake of oxidant drugs (including salicylates and sulfonamides). Diagnosis is based on assay for G6PD, although tests are often falsely negative during acute hemolysis. Treatment is supportive.

The only important defect in the hexose monophosphate shunt pathway is caused by G6PD deficiency. Over 100 mutant forms of the enzyme have been identified. Clinically, the most common form is the drug-sensitive variety. This X-linked disorder is fully expressed in males and homozygous females and is variably expressed in heterozygous females. This defect occurs in about 10% of black males and in < 10% of black females in the US and in lower frequencies among people with ancestors from the Mediterranean basin (eg, Italians, Greeks, Arabs, Sephardic Jews).

Pathophysiology

G6PD deficiency reduces energy available to maintain the integrity of the red cell membrane, which shortens RBC survival.

Hemolysis selectively affects older RBCs among affected blacks and among most affected whites. Hemolysis occurs commonly after fever, acute viral and bacterial infections, and diabetic acidosis. Less commonly, hemolysis occurs after exposure to drugs or to other substances that produce peroxide and cause oxidation of Hb and RBC membranes. These drugs and substances include primaquineSome Trade Names
No US trade name
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, salicylates, sulfonamides, nitrofurans, phenacetin, naphthalene, some vitamin K derivatives, dapsoneSome Trade Names
ACZONE
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, phenazopyridineSome Trade Names
PYRIDIUM
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, nalidixic acidSome Trade Names
NEGGRAM

, methylene blueSome Trade Names
UROLENE BLUE
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, and, in some whites, fava beans. Whether continued use of the offending drug leads to a compensated hemolytic state or lethal hemolysis depends on the degree of G6PD deficiency and the oxidant potential of the drug. Chronic congenital hemolysis (without drug use) occurs in some whites. Because older cells are selectively destroyed in blacks, hemolysis is usually self-limited, affecting < 25% of RBC mass; in whites, the deficiency is more severe, and profound hemolysis may lead to hemoglobinuria and acute renal failure.

Diagnosis

• G6PD assay

The diagnosis is considered in patients with acute hemolysis, particularly black males. G6PD assay is done. Anemia, jaundice, and reticulocytosis develop during hemolysis. Heinz bodies, possibly particles of dead cytoplasm or denatured Hb, may be visible early during the hemolytic episode but do not persist in patients with an intact spleen because they are removed by it. A specific diagnostic clue is the presence in the peripheral blood of RBCs that appear to have had one or more bites (1-μm wide) taken from the cell periphery (bite cells), possibly as a result of Heinz body removal by the spleen. Many screening tests are available. However, during and immediately after a hemolytic episode, tests may yield false-negative results because of destruction of the older, more deficient RBCs and the presence of reticulocytes rich in G6PD. Specific enzyme assays are the best diagnostic tests.

Treatment

During acute hemolysis, treatment is supportive; transfusions are rarely needed. Patients are advised to avoid drugs or substances that initiate hemolysis.

Last full review/revision February 2009 by Alan E. Lichtin, MD

Content last modified February 2012