A term male neonate becomes lethargic and refuses feeds on day 2, then develops seizures and coma. Blood gas shows respiratory alkalosis, plasma ammonia is 950 micromol/L, blood urea nitrogen is 2 mg/dL, and urinary orotic acid is markedly elevated. Which enzyme deficiency is most likely?
- A Carbamoyl phosphate synthetase I
- B Argininosuccinate synthetase
- C Ornithine transcarbamylase ✓
- D Arginase
Correct answer: C. Ornithine transcarbamylase
Explanation
Ornithine transcarbamylase deficiency, the commonest urea cycle disorder and the only one that is X-linked, blocks conversion of carbamoyl phosphate to citrulline. Mitochondrial carbamoyl phosphate escapes into the cytosol and drives pyrimidine synthesis, producing orotic aciduria. Carbamoyl phosphate synthetase I deficiency also causes neonatal hyperammonaemia but with normal or low orotic acid, which is the discriminating finding here.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.