Studies of the cause and treatment of hyperammonemia in females with ornithine transcarbamylase deficiency.

Assay of ornithine transcarbamylase (OTC) activity in multiple small bits of liver (approximately 5 mg) that were obtained from a single surgical biopsy in a patient with OTC deficiency revealed a 10- to 40-fold variation in enzyme activity. Similar studies with control autopsy liver specimens varied 2.5-fold at most. The greater variation in the patient with OTC deficiency probably is due to sampling of clusters of normal or abnormal hepatocytes that resulted from inactivation of either the abnormal or normal X chromosone. Enzyme activity assayed on small liver biopsy specimens may not be representative of the entire liver in female patients with OTC deficiency. The hyperammonemia in individuals heterozygous for OTC deficiency may be due in part to shunting of blood through multiple "metabolic portosystemic shunts." Treatment of a girl who has OTC deficiency with a low-protein diet, a low-protein diet supplemented with oral essential amino acids, and a low-protein diet plus oral ketoacids of essential amino acids, on a separate occasion, a low-protein diet was compared to a low-protein diet plus lactulose. The low-protein diet plus oral ketoacid supplementation resulted in the best metabolic control of the patient's disease. On the other hand, paradoxical transient hyperammonemia was observed after the intarvenous administration of ketoacids to two acutely ill female patients with OTC deficiency.