Free Step 1-style question
Older adult with megaloblastic anemia and posterior column findings; tests the metabolite that distinguishes this deficiency from folate deficiency.
A 68-year-old woman is evaluated for progressive fatigue, numbness in her feet, and unsteadiness that is worse when walking in the dark. Examination shows a smooth erythematous tongue, decreased vibration sense in both feet, and a broad-based gait. Peripheral blood smear shows macro-ovalocytes and hypersegmented neutrophils.
| Test | Value | Reference range |
|---|---|---|
| Hemoglobin | 9.4 g/dL | 12.0–15.5 g/dL |
| Mean corpuscular volume | 116 fL | 80–100 fL |
Which of the following metabolite accumulations is most specific for this patient's underlying deficiency?
- A. Accumulation of branched-chain alpha-ketoacids
- B. Accumulation of homogentisic acid
- C. Accumulation of methylmalonic acid
- D. Accumulation of orotic acid
- E. Accumulation of phenylpyruvate
Correct answer: C. Accumulation of methylmalonic acid
Progressive fatigue, numbness, gait instability worse in the dark, glossitis, decreased vibration sense, macro-ovalocytes, and hypersegmented neutrophils in an older adult point to vitamin B12 deficiency with megaloblastic anemia and subacute combined degeneration. Vitamin B12 is required as adenosylcobalamin for methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA during metabolism of odd-chain fatty acids and certain amino acids, including valine, isoleucine, methionine, and threonine. Deficiency impairs this reaction, causing methylmalonyl-CoA and methylmalonic acid accumulation. Vitamin B12 deficiency also impairs methionine synthase and can increase homocysteine, but methylmalonic acid accumulation is more specific because folate deficiency can also cause megaloblastic anemia and elevated homocysteine without impairing methylmalonyl-CoA mutase.
Takeaway
Vitamin B12 deficiency causes methylmalonic acid accumulation by impairing adenosylcobalamin-dependent methylmalonyl-CoA mutase. Elevated methylmalonic acid distinguishes vitamin B12 deficiency from folate deficiency, which can also cause megaloblastic anemia and elevated homocysteine.
What this page covers
Practice Step 1-style biochemistry questions on Vitamin B12 deficiency, with emphasis on metabolic consequence / accumulation / deficiency and answer-choice reasoning.
Step 1 practice focus
This preview is organized around Vitamin B12 deficiency in Water-Soluble Vitamins within Vitamins & Cofactors. It is intended for students practicing metabolic consequence / accumulation / deficiency questions, where the goal is to connect the vignette clue pattern to the underlying biochemical pathway, enzyme defect, metabolite change, regulatory step, or physiologic consequence.
How to use this page
Review the topic and reasoning focus, then practice Step 1-style questions inside BiochemStep. The question set emphasizes mechanism-first answer-choice reasoning rather than passive content review.