Urea cycle defects and hyperammonemia: effects on functional imaging
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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.
KeywordsUrea cycle disorders Brain MRI
This consortium, the Urea Cycle Disorders Consortium, is a part of the NIH Rare Diseases Clinical Research Network (RDCRN). Funding and/or programmatic support for this project has been provided by U54HD061221, subproject 5966 from the National Institute of Child Health and Human Development (NICHD) and the NIH Office of Rare Diseases Research (ORDR). The views expressed in written materials or publications do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.
This study was also funded by a NCRR career development award K12RR17613 and funded by U54RR019453 and 1M01RR020359-010058. We thank Rebecca R. Seltzer, Ayichew Hailu, and Dr. Bennett Gertz for technical assistance. The authors thank the subjects for their participation, and the NUCDF, in particular, Ms. Cynthia LeMons, for enthusiasm for the study. We thank the study coordinators and Principal investigators of the UCRDC for referral of subjects.
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