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Semin Neurol 2014; 34(03): 341-349
DOI: 10.1055/s-0034-1386771
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Urea Cycle Disorders

Guy Helman
1   Department of Neurology, Children's National Medical Center, Washington, District of Columbia
2   Department of Neurology, Georgetown University Medical Center, Washington, District of Columbia
,
Ileana Pacheco-Colón
2   Department of Neurology, Georgetown University Medical Center, Washington, District of Columbia
3   Center for Functional and Molecular Imaging, Georgetown University Medical Center, Washington, District of Columbia
,
Andrea L. Gropman
1   Department of Neurology, Children's National Medical Center, Washington, District of Columbia
4   Department of Genetics and Metabolism, Children's National Medical Center, Washington, District of Columbia
5   The George Washington University of the Health Sciences, Washington, District of Columbia
› Author Affiliations
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Publication History

Publication Date:
05 September 2014 (online)

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Abstract

The urea cycle is the primary nitrogen-disposal pathway in humans. It requires the coordinated function of six enzymes and two mitochondrial transporters to catalyze the conversion of a molecule of ammonia, the α-nitrogen of aspartate, and bicarbonate into urea. Whereas ammonia is toxic, urea is relatively inert, soluble in water, and readily excreted by the kidney in the urine. Accumulation of ammonia and other toxic intermediates of the cycle lead to predominantly neurologic sequelae. The disorders may present at any age from the neonatal period to adulthood, with the more severely affected patients presenting earlier in life. Patients are at risk for metabolic decompensation throughout life, often triggered by illness, fasting, surgery and postoperative states, peripartum, stress, and increased exogenous protein load. Here the authors address neurologic presentations of ornithine transcarbamylase deficiency in detail, the most common of the urea cycle disorders, neuropathology, neurophysiology, and our studies in neuroimaging. Special attention to late-onset presentations is given.

Keywords

urea cycle disorders - cognitive function - asymptomatic carriers - metabolic disease - ornithine transcarbamylase deficiency
 

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