Citation: Gyato K, Wray J, Huang ZJ, Yudkoff M, Batshaw ML. Metabolic and neuropsychological phenotype in women heterozygous for ornithine transcarbamylase deficiency. Ann Neurol. 2004;55(1):80-86. doi:10.1002/ana.10794.
Purpose: To better understand hyperammonemic-induced cognitive and behavior alterations in 19 women (aged 21 to 53 years) heterozygous for ornithine transcarbamylase (OTC) deficiency.
- Although patients in this study had normal IQs,a they showed a specific neuropsychologicalb phenotype. Relative to normative values, these patients showed a significant decline in fine motor function and nonsignificant weaknesses in nonverbal memory and learning, math, and attention/executive function. In contrast, performance was significantly above normal for verbal memory, verbal learning, reading, and verbal intelligence.
- Both symptomatic (n=8) and “asymptomatic” (n=11) patients showed a similar neuropsychological phenotype, although the “asymptomatic” patients had greater preservation of strengths and less marked deficits. Neuropsychological outcome was not associated with neonatal vs late-onset mutation, and there were limited associations with urea synthesis capacity.
- The allopurinol challenge test, which measures orotic acid excretion and can provide a measure of impairment of urea synthesis activity, was not sensitive enough to yield statistically significant results that could distinguish symptomatic from “asymptomatic” patients identified by clinical symptoms.
- The neurobehavioral phenotype exhibited by the patients with heterozygous OTC deficiency in this study is similar to that seen in patients with a nonverbal learning disability, which is often characterized by deficits associated with disturbances in white matter, including attention/executive weaknesses along with motor, tactile, and visual-spatial deficiencies.
- At the time of publication, alterations of white matter in patients with late-onset OTC deficiency had been shown by neuroimaging and neuropathological studies.1,2 In combination with the neurocognitive data presented in the current study, these findings add to the evidence of a white matter damage model for this disorder.
bPatients performed 9 different neuropsychological tests, and individual scores for each test were assigned to a corresponding functional domain, including verbal intelligence, fine motor skill, and attention/executive function, based on conventional clinical practice.
Additional references: 1. Kurihara, et al. Brain Dev. 2003;25(1):40-44. 2. Kornfield, et al. Acta Neuropathol. 1985;65:261-264.