ABSTRACT
Pyruvate carboxylase is an important regulatory enzyme with highly tissue-specific roles. In liver and kidney, where its activity is highest, it catalyzes the first step in gluconeogenesis from pyruvate in which the oxaloacetate formed is converted via phosphoenolpyruvate carboxykinase to phosphoenolpyruvate, and ultimately to glucose and glycogen. Deficiency of pyruvate carboxylase was first described in patients with Leigh syndrome. All forms of pyruvate carboxylase deficiency appear to be inherited in an autosomal recessive fashion. A founder effect has been postulated for the abnormal gene in the Canadian Indians. Metabolic acidosis and renal tubular acidosis have been treated in most patients with sodium bicarbonate. In acute episodes, parenteral fluids are required. Supplementation with aspartic acid appears to be a rational approach to a shortage of oxalacetate. Treatment with dichloroacetic acid is effective in ameliorating the lactic acidemia. Hepatic transplantation abolished the renal tubular acidosis, as well as the ketoacidosis.
