Maple syrup urine disease (MSUD) results from deficiency of branched-chain alpha-keto acid dehydrogenase (BCKDH). Which cofactor deficiency would phenotypically mimic MSUD by secondarily impairing BCKDH function?

• A Biotin deficiency
• B Riboflavin (vitamin B2) deficiency
• C Pyridoxine (vitamin B6) deficiency
• D Thiamine (vitamin B1) deficiency ✓

Explanation

BCKDH is a multienzyme complex analogous to pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, requiring thiamine pyrophosphate (TPP) as an essential cofactor (for the E1 component). Severe thiamine deficiency impairs BCKDH activity, causing secondary accumulation of branched-chain amino acids and their keto acids, partially mimicking MSUD. Thiamine-responsive MSUD is a recognized variant where pharmacological thiamine doses stabilize the residual enzyme activity. Biotin is required for carboxylases (acetyl-CoA carboxylase, pyruvate carboxylase).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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