Ammonia storm: unmasking a suspected rare proximal urea cycle disorder in adulthood

Hyperammonaemia is a medical emergency which is mostly associated with liver dysfunction. However, in the absence of hepatic disease, rare inborn errors of metabolism such as urea cycle disorders (UCDs) must be considered. While UCDs typically present in the neonatal period, partial enzyme deficiencies may remain clinically silent until adulthood and present abruptly with life-threatening hyperammonaemia encephalopathy. Among these, late-onset carbamoyl phosphate synthetase I (CPS-I) deficiency is exceedingly rare and often underdiagnosed.

We report a 32-year-old male who presented with acute onset altered sensorium progressing to coma over 12 h. The neurological decline was preceded by two to three episodes of vomiting on the day of admission and a recent history of a five-to-six-day febrile illness accompanied by gastrointestinal symptoms. On admission, the patient had a Glasgow Coma Scale score of 7/15 and required endotracheal intubation with ventilatory support. Routine laboratory investigations, including liver and renal function tests, were within normal limits. Neuroimaging studies (CT and MRI brain) showed no abnormalities. Plasma ammonia was markedly elevated at 397 µg/dL (Normal: <50 µg/dL), which rapidly escalated to 804 µg/dL within 24 h despite initial pharmacological intervention. Further metabolic evaluation revealed low plasma citrulline, elevated glutamine levels, and low urinary orotic acid, suggestive of a proximal urea cycle defect such as carbamoyl phosphate synthetase I (CPS-I) or N-acetylglutamate synthase (NAGS) deficiency. A significant family history of consanguinity and unexplained neonatal death, further supported a genetic etiology. The patient underwent urgent haemodialysis for ammonia clearance and was treated with protein restriction, dextrose-based intravenous fluids, and ammonia-lowering agents including sodium benzoate. His neurological status improved progressively, allowing successful extubation after three days. He was later discharged on oral L-citrulline supplementation and dietary protein restriction. At two-week follow-up, he was clinically stable with normalized plasma ammonia levels.

This case highlights the importance of considering late-onset urea cycle disorders in adults presenting with unexplained hyperammonaemia encephalopathy. Early recognition and prompt aggressive management can be lifesaving and lead to complete neurological recovery.