Neurometabolic Disorders: Urea-Cycle Disorder, Outcomes, Development and Treatment

Abstract

The urea-cycle disorders (UCDs) are a group of congenital enzyme and carrier deficiencies predisposing to fatal hyperammonemia. Hyperammonemia causes alterations of neurotransmitter function and cell volume, leading to cerebral edema. Neuropathological findings of UCDs reflect changes in astrocyte morphology. Neurological features accompanying acute hyperammonemia include changes in behavior and consciousness in the short term, and potential for impairments in memory and executive function as long-term effects. Plasma measures of ammonia and glutamine, although useful for clinical monitoring, are poor markers of CNS function. Treatment combines dietary protein restriction and nitrogen-scavenging agents. Despite this regimen, patients remain at risk for repeated hyperammonemic events and further neurological damage. Thus, neuroprotective strategies should be explored as adjunctive therapies.