Urea cycle disorders in critically Ill adults

Purpose of review Urea cycle disorders (UCDs) cause elevations in ammonia which, when severe, cause irreversible neurologic injury. Most patients with UCDs are diagnosed as neonates, though mild UCDs can present later - even into adulthood - during windows of high physiologic stress, like critical illness. It is crucial for clinicians to understand when to screen for UCDs and appreciate how to manage these disorders in order to prevent devastating neurologic injury or death. Recent findings Hyperammonemia, particularly if severe, causes time- and concentration-dependent neurologic injury. Mild UCDs presenting in adulthood are increasingly recognized, so broader screening in adults is recommended. For patients with UCDs, a comprehensive, multitiered approach to management is needed to prevent progression and irreversible injury. Earlier exogenous clearance is increasingly recognized as an important complement to other therapies. Summary UCDs alter the core pathway for ammonia metabolism. Screening for mild UCDs in adults with unexplained neurologic symptoms can direct care and prevent deterioration. Management of UCDs emphasizes decreasing ongoing ammonia production, avoiding catabolism, and supporting endogenous and exogenous ammonia clearance. Core neuroprotective and supportive critical care supplements this focused therapy.