title: Urea cycle defects and hyperammonemia: effects on functional imaging.
abstract: The urea-cycle disorders (UCDs) are a group of congenital enzyme and carrier deficiencies predisposing to hyperammonemia (HA). HA causes changes in the central nervous system (CNS) including alterations of neurotransmitter function, cell volume, and energy deprivation ultimately leading to cerebral edema. Neuropathological findings of UCDs primarily reflect changes in astrocyte morphology. Neurological features accompanying acute HA 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, prove poor markers of CNS function. Multimodal neuroimaging has potential to investigate impact on cognitive function by interrogating neural networks, connectivity and biochemistry. As neuroimaging methods become increasingly sophisticated, they will play a critical role in clinical monitoring and treatment of metabolic disease. We describe our findings in UCDs; with focus on Ornithine Transcarbamylase deficiency (OTCD) the only X linked UCD.
authors.affiliation: Department of Neurology, Children's National Medical Center, George Washington University of Health Sciences, 111 Michigan Avenue, NW, Washington, DC 20010, USA. agropman@childrensnational.org
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Gropman
authors.forename: Morgan
authors.initials: M
authors.lastname: Prust
authors.forename: Andrew
authors.initials: A
authors.lastname: Breeden
authors.forename: Stanley
authors.initials: S
authors.lastname: Fricke
authors.forename: John
authors.initials: J
authors.lastname: VanMeter
mesh_terms: D001288:Attention / Q000502:physiology; D001921:Brain / Q000473:pathology; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D038524:Diffusion Magnetic Resonance Imaging; D056344:Executive Function / Q000502:physiology; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D022124:Hyperammonemia / Q000473:pathology* / Q000523:psychology; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D011788:Quality of Life; D026361:Reactive Nitrogen Species / Q000378:metabolism; D056806:Urea Cycle Disorders, Inborn / Q000473:pathology* / Q000523:psychology
chemical_list: D016166:Free Radical Scavengers; D026361:Reactive Nitrogen Species