Hyperammonemia from a Urea Cycle Disorder Presenting in Adulthood

OBJECTIVE: The aim of this report is to describe a patient with late presentation of carbamyl phosphate synthetase I (CPS-I, EC 6.3.4.16) deficiency, a rare urea cycle deficiency, and to facilitate recognition and treatment of patients presenting with encephalopathy and hyperammonemia in a critical care setting. DESIGN: Case Report. SETTING: Intensive care unit of Saint Mary’s Hospital, Mayo Clinic, Rochester, Minnesota. PATIENT: A 65-year-old woman admitted with progressive encephalopathy. INTERVENTIONS: Intubation and mechanical ventilation, protein-restricted parenteral nutrition, intravenous arginine, hemodiafiltration, and intravenous antibiotic therapy. MEASUREMENTS AND MAIN RESULTS: Serum ammonia and glutamine levels were elevated, but other laboratory and imaging investigations were unremarkable. Despite the above interventions, her mental status deteriorated. She developed ventilator associated pneumonia, which worsened despite antibiotic treatment. The family decided to withdraw care and the patient expired on hospital day 10. A postmortem enzyme assay on fresh-frozen liver tissue showed severely diminished CPS-I activity. CONCLUSIONS: To our knowledge, this is the oldest reported age at presentation of CPS-I deficiency. Urea cycle disorders should be part of the differential diagnosis of hyperammonemia regardless of age as early treatment may ameliorate mortality and morbidity in these patients.