A newborn is identified on tandem mass spectrometry screening with elevated C5-carnitine (isovalerylcarnitine). Urine organic acids show isovalerylglycine and 3-hydroxyisovalerate. This pattern is diagnostic of:

• A 3-methylcrotonyl-CoA carboxylase deficiency
• B 3-methylglutaconic aciduria
• C Isovaleric acidemia (isovaleryl-CoA dehydrogenase deficiency) ✓
• D Propionic acidemia

Explanation

Isovaleryl-CoA dehydrogenase deficiency (isovaleric acidemia) impairs the third step of leucine catabolism, causing accumulation of isovaleryl-CoA. This is conjugated with carnitine (→ C5-carnitine) and with glycine (→ isovalerylglycine), both of which are elevated in plasma/urine. The characteristic 'sweaty feet' odour is from isovaleric acid. 3-methylcrotonyl-CoA carboxylase deficiency also affects leucine catabolism but produces 3-methylcrotonylglycine and 3-hydroxyisovalerate without elevated isovalerylglycine. Propionic acidemia produces C3-carnitine (propionylcarnitine).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.