Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy that leaves red cells unable to buffer oxidative stress, producing episodic intravascular hemolysis with bite cells and Heinz bodies after infection, fava beans, or oxidant drugs. Diagnosis rests on a G6PD enzyme activity assay that can be falsely normal during the acute episode and must be repeated 2 to 3 months later, while management centers on trigger avoidance, supportive care, and transfusion for severe hemolysis.
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What this article covers
- Overview
Definition: glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy of the hexose monophosphate shunt that impairs regeneration of NADPH and reduced glutathione, leaving red…
- Epidemiology
X-linked, so predominantly affects males: hemizygous males express the deficiency fully, while heterozygous females are typically mosaic and usually asymptomatic or mildly affected due to random X-inactivation (lyonization).
- Risk factors
Male sex: the single strongest risk factor given X-linked recessive inheritance.
- Pathophysiology
Enzyme defect: G6PD catalyzes the rate-limiting step of the hexose monophosphate shunt, oxidizing glucose-6-phosphate while reducing NADP+ to NADPH; a deficient enzyme cannot keep pace with oxidative demand.
- Clinical features
Acute hemolytic episode 1 to 3 days after oxidative exposure: sudden-onset fatigue, pallor, jaundice, and dark (tea- or cola-colored) urine from hemoglobinuria, in a patient who was previously well.
- Differential diagnosis
Autoimmune hemolytic anemia: jaundice, anemia, and reticulocytosis similar to G6PD deficiency, but with a positive direct antiglobulin (Coombs) test and spherocytes rather than bite cells (hemolytic anemia overview).
- Diagnosis
Confirm with a quantitative G6PD enzyme activity assay, a semiquantitative or fluorescent spot test measuring the reduction of NADP+ to NADPH; low activity establishes the diagnosis, but a normal…
- Management
Remove or treat the trigger first: stop any offending oxidant drug and treat the precipitating infection, which is the single most important step and is usually sufficient on its own.
- Complications
Acute kidney injury: from hemoglobin-induced tubular injury during brisk intravascular hemolysis, particularly with inadequate hydration.
- Prognosis
Excellent for the typical episodic adult presentation: hemolysis is usually self-limited, with hemoglobin recovering over days once the trigger is removed, because the enzyme defect does not affect…
- Prevention
Identify at-risk patients before prescribing high-risk drugs: screen for G6PD deficiency (or check prior documented status) in patients of African, Mediterranean, Middle Eastern, or Asian descent…
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