Megaloblastic and macrocytic anaemia: Viva

Branch 1: Confirming the diagnosis

The candidate should recognise the classic infantile vitamin B12 deficiency, with the macrocytic anaemia, the hypersegmented neutrophils, the developmental regression, and the tremor, in the breastfed infant of a strict vegan mother. A strong candidate states that the breastfeeding infant is wholly dependent on maternal stores, that a marginal vegan supply is depleted within months, and that the developmental regression is the sign that lifts the case out of an ordinary anaemia and marks the urgency. The candidate should add that the methylmalonic acid raised with the homocysteine raised confirms B12 rather than folate deficiency. ^[8][9]

If the examiner presses on the separation of the two deficiencies, the candidate should give the metabolite logic precisely. Methylmalonic acid rises only in B12 deficiency, because B12 is the cofactor for methylmalonyl-CoA mutase, while homocysteine rises in both deficiencies, because the methionine synthase step is shared and requires both vitamins. The candidate should note that the metabolites resolve the diagnosis when the serum B12 is borderline, which it often is, because the assay is confounded by pregnancy and liver disease. ^[5]