Emerging neurological and cognitive symptoms in patients with late-onset ornithine transcarbamylase deficiency: a narrative review

Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked urea cycle disorder associated with mild-to-severe neurological/cognitive symptoms that impact quality of life. Most patients are diagnosed with late-onset OTCD after 28 days of age. Emerging symptoms in adolescents and adults may not be recognized as effects of hyperammonemia, a common and potentially lethal complication of OTCD, and may contribute to substantial burden even when patients are diagnosed and treated. However, current reviews do not address this burden. Our aim is to raise awareness of neurological/cognitive manifestations of late-onset OTCD in adolescents and adults to reduce diagnostic delays and improve outcomes. Acutely, patients can present with signs of neurological impairment and psychiatric manifestations, which may be associated with a specific trigger or without known cause. Cognitive changes are more likely to be subacute or chronic, and onset may occur after hyperammonemia. As many late-onset OTCD cases are identified after presenting to emergency departments or primary care providers (often followed by hospital admission), education of frontline providers is needed to drive awareness, recognize symptoms, and improve patient care.