Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts.

Individuals with a proximal urea cycle disorder, such as carbamoyl phosphate synthetase deficiency 1 or ornithine transcarbamylase deficiency, may present with encephalopathy resulting from hyperammonemia. The clinical presentation of arginase deficiency is considerably different, characterized by progressive spasticity involving the lower extremities and usually dementia. Diagnosis may be delayed, and patients are often thought to have cerebral palsy. The true etiology of brain injury in arginase deficiency is unknown, but is not thought to be due to hyperammonemia and brain swelling, the mechanism of injury recognized in ornithine transcarbamylase deficiency. Elevated arginine could augment nitric oxide synthesis, leading to oxidative damage. The hypothesis for the present study was that specific brain vulnerability in arginase deficiency would involve microstructural alterations in corticospinal tracts and that this finding, as measured by diffusion tensor imaging, would differ from age-matched control subjects and those with ornithine transcarbamylase deficiency. Diffusion tensor imaging data were compared for a 17-year-old male patient with arginase deficiency, age-matched normal control subjects, and age-matched individuals with ornithine transcarbamylase deficiency. Significant differences were found in suspected areas of interest, specifically in the corticospinal tracts. This finding confirms the hypothesis that the mechanism of injury in arginase deficiency, although still unknown, is unlikely to be similar to that causing ornithine transcarbamylase deficiency.