A student asks how to distinguish folate deficiency from vitamin B12 deficiency on laboratory testing. Both deficiencies elevate which metabolite, while only B12 deficiency elevates which other metabolite?

• A Neither raises homocysteine; both raise methylmalonic acid
• B Both raise methylmalonic acid; only folate deficiency raises homocysteine
• C Both raise homocysteine; only folate deficiency raises methylmalonic acid
• D Both raise homocysteine; only B12 deficiency raises methylmalonic acid ✓

Explanation

Folate as methyl-tetrahydrofolate donates a methyl group to convert homocysteine to methionine, so both deficiencies trap homocysteine. Vitamin B12 is also the cofactor for methylmalonyl-CoA mutase, so methylmalonic acid accumulates only in B12 deficiency. This single fact explains why B12 deficiency causes neurologic damage while folate deficiency does not, since MMA impairs myelin maintenance.

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

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