G6PD deficiency and enzymopathies: Viva

Branch 1: Recognising the problem and the mechanism

The candidate should immediately recognise this as a direct-antiglobulin-test-negative intravascular haemolysis in a boy of African ancestry after a viral trigger, which places G6PD deficiency at the top of the differential. The combination of sudden jaundice, dark urine, pallor, a high reticulocyte count, a negative direct antiglobulin test, and bite cells with Heinz bodies is the blood-film signature of oxidative haemolysis. The candidate should state the diagnosis aloud as the problem representation and confirm that the film findings are pathognomonic when combined with the negative direct antiglobulin test. ^[1]

The examiner will probe the mechanism. The candidate should explain that G6PD generates NADPH through the pentose phosphate pathway, that NADPH keeps glutathione reduced, and that reduced glutathione neutralises the oxidants generated in the red cell. In deficiency, oxidants denature haemoglobin into Heinz bodies, the spleen pits them out to form bite cells, and the membrane lyses. The candidate should explain why red cells are uniquely vulnerable, namely that they have no nucleus and cannot replace the deficient enzyme, so the oldest cells with the least residual activity are lysed first. ^[1][2]