A 28-year-old Ghanaian man presents with haemolytic crisis after taking primaquine. G6PD enzyme deficiency leads to haemolysis by which mechanism?

• A Inhibition of hexokinase reducing glycolytic ATP, causing ion pump failure and osmotic lysis
• B Accumulation of 6-phosphogluconate directly denaturing spectrin
• C G6PD deficiency impairs NADH-methemoglobin reductase, causing methemoglobin accumulation
• D Depletion of NADPH, impairing glutathione regeneration and allowing oxidative damage to haemoglobin ✓

Explanation

G6PD is the rate-limiting enzyme of the hexose monophosphate shunt and the sole source of NADPH in red cells, which are devoid of mitochondria. NADPH maintains glutathione in its reduced (active) form through glutathione reductase. In G6PD deficiency, oxidant stress (drugs, infection) cannot be neutralised because reduced glutathione is depleted; oxidative damage denatures haemoglobin into Heinz bodies, which cause membrane rigidity and direct lysis or splenic sequestration. Bite cells on peripheral smear reflect splenic removal of Heinz bodies.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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