A 2-year-old child presents with recurrent hospitalizations for hyperammonemia, irritability, and vomiting since infancy. Plasma amino acids show elevation of citrulline to >1000 μmol/L, with low argininosuccinate and low arginine. Urine orotic acid is elevated. The enzyme deficiency causing this condition is:
- A Carbamoyl phosphate synthetase I (CPS I)
- B Ornithine transcarbamylase (OTC)
- C Argininosuccinate synthetase (ASS) ✓
- D Argininosuccinate lyase (ASL)
Explanation
Citrullinemia type I is caused by deficiency of argininosuccinate synthetase (ASS), which catalyzes the condensation of citrulline with aspartate to form argininosuccinate. The enzymatic block leads to massive accumulation of citrulline (>1000 μmol/L) — the substrate immediately before the block. Urine orotic acid is elevated because excess carbamoyl phosphate spills into the pyrimidine synthesis pathway. OTC deficiency also causes high orotic acid but leads to low citrulline (citrulline is downstream of OTC). CPS I deficiency causes high ammonia with low citrulline and no orotic aciduria. ASL deficiency causes argininosuccinic aciduria.
Reference: Ghai Essential Pediatrics, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.