A 36-hour-old term male neonate becomes lethargic, refuses feeds, and develops seizures and tachypnea. Blood gas shows pH 7.48, pCO2 28 mm Hg. Plasma ammonia is 720 µmol/L, blood urea nitrogen is 2 mg/dL, plasma citrulline is very low, and urinary orotic acid is markedly elevated. Which enzyme is deficient?
- A Carbamoyl phosphate synthetase I
- B Argininosuccinate synthetase
- C Ornithine transcarbamylase ✓
- D Argininosuccinate lyase
Explanation
Ornithine transcarbamylase deficiency, the most common urea cycle disorder, is X-linked and presents in male neonates with hyperammonemic encephalopathy and respiratory alkalosis. Mitochondrial carbamoyl phosphate escapes into the cytosol and drives pyrimidine synthesis, causing elevated urinary orotic acid. This separates it from carbamoyl phosphate synthetase I deficiency, which also gives low citrulline but normal orotic acid. Argininosuccinate synthetase deficiency (citrullinemia) shows massively elevated citrulline, and argininosuccinate lyase deficiency adds argininosuccinic acid.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.