Biotin deficiency may result from avidin in raw egg white, prolonged TPN without biotin supplementation, or biotinidase deficiency. Biotinidase deficiency impairs recycling of biotin, causing multiple carboxylase deficiency. Which set of carboxylases is affected, and what is the diagnostic metabolite pattern?

• A Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase; elevated pyruvate and alpha-ketoglutarate only
• B Propionyl-CoA carboxylase and acetyl-CoA carboxylase only; elevated propionate and malonyl-CoA
• C Pyruvate carboxylase alone; isolated hyperlactatemia
• D Pyruvate carboxylase, propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, and acetyl-CoA carboxylase; elevated lactate, methylcitrate, 3-methylcrotonylglycine, and 3-hydroxyisovalerate ✓

Explanation

Biotin is the prosthetic group for all four mitochondrial/cytosolic carboxylases: pyruvate carboxylase (gluconeogenesis/TCA anaplerosis), propionyl-CoA carboxylase (odd-chain FA/branched-chain AA catabolism), 3-methylcrotonyl-CoA carboxylase (leucine catabolism), and acetyl-CoA carboxylase (fatty acid synthesis). Biotinidase cleaves biotin from biocytin (biotinyl-lysine) derived from dietary protein and enzyme turnover, recycling free biotin. Its deficiency causes multi-carboxylase deficiency with characteristic organic aciduria including 3-hydroxyisovalerate (from 3-methylcrotonyl-CoA carboxylase failure), methylcitrate and propionate (propionyl-CoA carboxylase failure), and lactic acidosis (pyruvate carboxylase failure). Treatment: pharmacologic oral biotin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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