A child with maple syrup urine disease (MSUD) is in metabolic crisis with encephalopathy and plasma leucine of 2800 micromol/L. The branched-chain alpha-keto acid dehydrogenase (BCKD) complex has a structure analogous to pyruvate dehydrogenase. Which cofactor common to both BCKD and pyruvate dehydrogenase is absent in this child's diet that could trigger a MSUD-like biochemical crisis even in a dietary-compliant patient?

• A Biotin
• B Pyridoxal phosphate (PLP)
• C Lipoic acid
• D Thiamine pyrophosphate (TPP) ✓

Explanation

The branched-chain alpha-keto acid dehydrogenase (BCKD) complex uses the same five cofactors as pyruvate dehydrogenase: thiamine pyrophosphate (E1 component), lipoic acid (E2 component), CoA (E2 component), FAD (E3 component), and NAD+ (E3 component). Of these, thiamine (vitamin B1) is a dietary requirement and cannot be synthesized by humans. Severe thiamine deficiency would impair both BCKD and pyruvate dehydrogenase, causing elevated branched-chain amino acids and their keto-acids (mimicking MSUD biochemically) along with lactic acidosis. This is clinically relevant in thiamine-deficient patients (alcoholism, hyperemesis) who may develop MSUD-like biochemical patterns. Biotin is required for carboxylase enzymes (not BCKD or PDH). PLP is required for aminotransferases.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.