A 2-day-old male infant develops lethargy, vomiting, seizures, and respiratory alkalosis. Plasma ammonia is 900 micromol/L, blood urea nitrogen is very low, and serum glucose and electrolytes are normal. Urine organic acids show markedly elevated orotic acid. Which enzyme is deficient?

• A Carbamoyl phosphate synthetase I
• B Ornithine transcarbamylase ✓
• C N-acetylglutamate synthetase
• D Argininosuccinate synthetase

Explanation

Ornithine transcarbamylase deficiency, the commonest urea cycle disorder, is X-linked and blocks conversion of carbamoyl phosphate to citrulline. Mitochondrial carbamoyl phosphate escapes to the cytosol and enters pyrimidine synthesis, producing elevated orotic acid in urine. CPS I deficiency and N-acetylglutamate synthetase deficiency cause hyperammonemia without orotic aciduria because the block precedes cytosolic escape. Argininosuccinate synthetase deficiency (citrullinemia) elevates citrulline, not orotate.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.