Eur J Paediatr Neurol. 2003 ; 7(3): 115-21.

Ornithine transcarbamylase deficiency: a urea cycle defect.

Gordon N.

Wilmslow, UK. neil-gordon@doctors.org.uk

The symptoms and signs of ornithine transcarbamylase deficiency are discussed. When the condition occurs among males in the neonatal period it is likely to be lethal. Pathological findings are non-specific. The diagnosis should be considered if coma with cerebral oedema and respiratory alkalosis occurs for no obvious reason. When hyperammonaemia is found, enzyme assay on a liver biopsy should be considered. A useful clue in an asymptomatic patient is a voluntary adoption of a vegetarian diet. Provocative tests, such as the allopurinol test can be used, but the method most frequently applied is mutation analysis. In the case of prenatal diagnosis this is possible on a chorionic villus sample.The prognosis of ornithine transcarbamylase deficiency is better for those with an onset after infancy, but morbidity from brain damage does not appear to be linked to the number of episodes of hyperammonaemia that have occurred.The syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase which catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. The gene responsible for this enzyme is located on Xp21.1, and is expressed in the liver and gut. Mutations can be divided into two groups: those with neonatal onset with all enzyme activity abolished, and those with later onset with partial and varying enzyme deficiency.There can be a variety of precipitating causes, for example sodium valproate. Treatment can be given with a low protein diet, and with alternate pathway drugs such as sodium benzoate and phenylbutyrate. Liver transplant can be considered when symptoms are life-threatening, although there may be severe complications.Gene replacement therapy is the hope of the future.