G6PD Deficiency

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the pentose phosphate pathway, generating NADPH essential for regenerating reduced glutathione that protects erythrocytes from oxidative damage. G6PD deficiency, the most common enzymopathy in the world (estimated 400 million people), is X-linked, affecting predominantly males; female carriers may have variable phenotype due to lyonization.

Multiple variants exist with differing severity: class I (severe, chronic non-spherocytic hemolytic anemia), class II (severe enzyme deficiency, episodic hemolysis — Mediterranean), class III (moderate — African A-), class IV-V (normal or mild). Geographic distribution overlaps with historical malaria endemic regions, suggesting selective advantage against Plasmodium falciparum.

Clinical scenarios include neonatal jaundice (sometimes severe with kernicterus risk), acute hemolytic anemia triggered by infections (most common), fava beans (favism — typically Mediterranean variant), and oxidant drugs (sulfa drugs, dapsone, primaquine, methylene blue, nitrofurantoin, aspirin in high dose, phenazopyridine). Diagnosis is by quantitative G6PD enzyme assay, ideally not during acute hemolysis when reticulocytes (with higher enzyme) may mask deficiency. Hemolytic episode features pallor, jaundice, dark or red urine, abdominal/back pain, anemia, bite cells and Heinz bodies on smear (with supravital stain), and reticulocytosis. Management is preventive: avoid trigger drugs and foods, treat infections promptly, and supportive care (hydration, transfusion if severe). Severe class I patients may require lifelong management for chronic hemolysis.