Methylmalonic acid accumulation in the urine is a characteristic finding of deficiency of which B vitamin?

Explanation

## Vitamin B₁₂ and Methylmalonic Acid Metabolism **Key Point:** Vitamin B₁₂ (cobalamin) is the coenzyme for methylmalonyl-CoA mutase, the enzyme that converts methylmalonyl-CoA to succinyl-CoA. Deficiency of B₁₂ leads to accumulation and urinary excretion of methylmalonic acid (methylmalonia). ## Metabolic Pathway and Deficiency Effects 1. **Normal metabolism:** Propionyl-CoA → Methylmalonyl-CoA → (via B₁₂-dependent mutase) → Succinyl-CoA → TCA cycle 2. **B₁₂ deficiency:** Methylmalonyl-CoA mutase activity ↓ → methylmalonic acid accumulates → urinary excretion 3. **Secondary effects:** Impaired TCA cycle function, reduced energy production, neurological damage ## Diagnostic Significance of Methylmalonic Acid **High-Yield:** Elevated urinary methylmalonic acid is a **specific biochemical marker** for B₁₂ deficiency and is used diagnostically to distinguish B₁₂ deficiency from folate deficiency (both cause megaloblastic anemia). **Mnemonic:** **MMA = B₁₂** — Methylmalonic Acid elevation = B₁₂ deficiency. ## B₁₂ Deficiency vs. Folate Deficiency — Differential Markers | Marker | B₁₂ Deficiency | Folate Deficiency | | --- | --- | --- | | Methylmalonic acid (urine) | ↑↑ | Normal | | Homocysteine (serum) | ↑↑ | ↑ | | Neurological symptoms | Yes (subacute combined degeneration) | No | | Megaloblastic anemia | Yes | Yes | **Clinical Pearl:** Homocysteine is elevated in both B₁₂ and folate deficiency, but methylmalonic acid is elevated **only** in B₁₂ deficiency — making it the discriminating test. **Warning:** Do not confuse with methylmalonic acidemia (genetic disorder of methylmalonyl-CoA mutase enzyme itself) — that is a primary enzyme defect, not a cofactor deficiency.