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

Abstract

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.

• Authors: Kuntal Sen, Matthew Whitehead, Carlos Castillo Pinto, Ljubica Caldovic, Andrea Gropman
• Journal: Analytical biochemistry (Anal Biochem) Vol. 636 Pg. 114343 (01 01 2022) ISSN: 1096-0309 [Electronic] United States
• PMID: 34637785 (Publication Type: Historical Article, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Topics

• Animals
• Brain (diagnostic imaging, metabolism, physiopathology)
• Electroencephalography
• History, 21st Century
• Hyperammonemia (diagnostic imaging, history, metabolism, physiopathology)
• Magnetic Resonance Imaging
• Proton Magnetic Resonance Spectroscopy
• Urea Cycle Disorders, Inborn (diagnostic imaging, history, metabolism, physiopathology)