A neonate presents with hyperammonaemia and orotic aciduria. Plasma citrulline is elevated. The most likely diagnosis is:
- A Argininosuccinate synthetase deficiency (Citrullinemia type 1) ✓
- B Carbamoyl phosphate synthetase I (CPSI) deficiency
- C Ornithine transcarbamylase (OTC) deficiency
- D Argininosuccinate lyase deficiency (Argininosuccinic aciduria)
Explanation
In citrullinemia type 1 (argininosuccinate synthetase deficiency), citrulline cannot be converted to argininosuccinate. Citrulline accumulates in plasma (markedly elevated) while downstream urea cycle intermediates are absent. Ammonia accumulates because the urea cycle is blocked after citrulline. Orotic aciduria occurs because excess carbamoyl phosphate (from cytosolic synthesis) enters the pyrimidine synthesis pathway, producing orotic acid. CPSI deficiency causes hyperammonaemia with low citrulline and no orotic aciduria. OTC deficiency causes hyperammonaemia, very low citrulline, and orotic aciduria (most common X-linked urea cycle defect). Argininosuccinate lyase deficiency (ASL) shows elevated argininosuccinate with elevated citrulline.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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Written and medically reviewed by the StethoPrep medical team.