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Functional B12 Deficiency — RACP Adult Medicine MCQ

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ModerateHaematologyFunctional B12 DeficiencyRACP Adult Medicine

A 58-year-old man undergoes investigation for macrocytic anaemia. His MCV is 115 fL. Vitamin B12 and folate are normal. Reticulocyte count is low. Blood film shows oval macrocytes and hypersegmented neutrophils. Bone marrow shows megaloblastic changes. What should be tested?

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Correct answer: A — Serum methylmalonic acid and homocysteine

Despite 'normal' serum B12 levels, functional B12 deficiency can occur (serum B12 may be falsely normal in 5–10% of B12-deficient patients). Methylmalonic acid (MMA) and homocysteine are the most sensitive markers: MMA is elevated in B12 deficiency (not folate deficiency), while homocysteine is elevated in both B12 and folate deficiency. The megaloblastic morphology (oval macrocytes, hypersegmented neutrophils) on blood film strongly suggests B12 or folate deficiency despite apparently normal levels. If MMA is elevated, a trial of B12 replacement is warranted.

Reference: eTG – 2025 – Haematology