Fifteen years of urea cycle disorders brain research: Looking back, looking forward

Urea cycle disorders (UCD) are inherited diseases resulting from deficiency in one of six enzymes or two carriers that are required to remove ammonia from the body. UCD may be associated with neurological damage encompassing a spectrum from asymptomatic/mild to severe encephalopathy, which results in most cases from Hyperammonemia (HA) and elevation of other neurotoxic intermediates of metabolism. Electroencephalography (EEG), Magnetic resonance imaging (MRI) and Proton Magnetic resonance spectroscopy (MRS) are noninvasive measures of brain function and structure that can be used during HA to guide management and provide prognostic information, in addition to being research tools to understand the pathophysiology of UCD associated brain injury. The Urea Cycle Rare disorders Consortium (UCDC) has been invested in research to understand the immediate and downstream effects of hyperammonemia (HA) on brain using electroencephalogram (EEG) and multimodal brain MRI to establish early patterns of brain injury and to track recovery and prognosis. This review highlights the evolving knowledge about the impact of UCD and HA in particular on neurological injury and recovery and use of EEG and MRI to study and evaluate prognostic factors for risk and recovery. It recognizes the work of others and discusses the UCDC's prior work and future research priorities.

Automated summary

UCD is a genetic disorder caused by deficiency in essential enzymes or carriers, leading to neurological damage ranging from mild to severe encephalopathy, primarily due to hyperammonemia and elevation of other neurotoxic intermediates. Noninvasive measures like EEG and MRI can assist in guiding management, providing prognostic information, and studying the pathophysiology of UCD-related brain injury. Utilizing EEG and multimodal brain MRI, UCDC focuses on understanding the immediate and downstream effects of hyperammonemia on brain function, establishing early patterns of brain injury, and tracking recovery and prognosis.