Unexplained hyperammonemia in the emergency department: Late-onset ornithine transcarbamylase deficiency in a 75-year-old man.

Late-onset ornithine transcarbamylase deficiency (OTCD) is an extremely rare X-linked urea cycle disorder in the geriatric population, and its diagnosis in the emergency department (ED) is highly challenging. We report the case of a 75-year-old man who presented to the ED with acute confusion and vomiting that rapidly progressed to coma. Initial investigations revealed unexplained hyperammonemia. Despite an empiric lactulose enema, his neurological status continued to deteriorate, and his plasma ammonia level peaked at 487 μmol/L. He required endotracheal intubation, and emergent hemodialysis was initiated. A detailed family history revealed that two nephews had died from unexplained hyperammonemia, raising a high index of suspicion for an inherited metabolic disorder. Subsequent plasma amino acid analysis revealed elevated ornithine and decreased citrulline levels. The diagnosis was confirmed by next-generation sequencing, which identified a hemizygous OTC variant (c.119G > A, p.Arg40His). The patient was successfully managed with hemodialysis, intravenous L-arginine, and a protein-restricted diet, and he was ultimately discharged without focal neurological sequelae. This case highlights that clinicians should consider urea cycle disorders in the differential diagnosis of unexplained hyperammonemia regardless of age, including in geriatric patients. Furthermore, it underscores the critical value of a comprehensive family history and the prompt initiation of hemodialysis-before genetic confirmation-to prevent irreversible neurological damage in atypical adult presentations.