Hyperammonemia caused by impaired mitochondrial ornithine transport in a patient with partial quantitative deficiency of ornithine carbamoyltransferase.

Late-onset hyperammonemia was observed in a male patient with partial quantitative deficiency of ornithine carbamoyltransferase (OCT). His liver contained 10% of the normal level of OCT, but with normal kinetics. This reduced enzyme activity alone, however, could not explain the hyperammonemia. Therefore, the effects of impaired ornithine transport into mitochondria, which seemed to be a possible precipitating factor, were examined by numerical simulation of the urea cycle. The results were as follows: (a) On the assumption that the ornithine concentrations in the cytosol and mitochondrial matrix were always equal, the ammonia handling efficiency would be unchanged by decrease in the OCT concentration to 10% of normal; (b) Under conditions of impaired mitochondrial ornithine transport that had no effects on ureagenesis with a normal amount of enzyme, 10% of the normal concentration of enzyme would impair ammonia handling efficiency. Thus, impaired mitochondrial ornithine transport seemed to cause hyperammonemia in the state of partial quantitative deficiency of OCT in this case.