Biotin-dependent carboxylases include pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase. Biotinidase deficiency causes acquired multiple carboxylase deficiency. Which metabolite accumulation is most useful in confirming this diagnosis?

• A Elevated phenylalanine and tyrosine due to impaired transamination
• B Elevated branched-chain amino acids (leucine, isoleucine, valine) in plasma
• C Elevated 3-methylcrotonylglycine and 3-hydroxyisovalerate in urine (from 3-methylcrotonyl-CoA carboxylase deficiency), plus methylcitrate from propionyl-CoA carboxylase deficiency ✓
• D Elevated long-chain acylcarnitines indicating beta-oxidation failure

Explanation

Biotinidase cleaves biocytin (biotin-lysine from degraded biotin-enzymes) to recycle free biotin. Deficiency causes secondary biotin deficiency, impairing all four biotin-dependent carboxylases. Propionyl-CoA carboxylase deficiency → methylcitric acid and 3-hydroxypropionic acid; 3-methylcrotonyl-CoA carboxylase deficiency → 3-methylcrotonylglycine and 3-hydroxyisovalerate; pyruvate carboxylase deficiency → lactic acidosis. The combination of these organic acids in urine is diagnostic. Biotinidase deficiency (vs. holocarboxylase synthetase deficiency) can present later in infancy and responds dramatically to pharmacological biotin supplementation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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