The biotin-dependent carboxylase deficiencies

The carboxylase deficiencies have recently received much attention because of their increased recognition by geneticists and physicians, ease of laboratory diagnosis, and potential for treatment by protein restriction and vitamin supplementation. Disorders characterized by deficiencies of the four known human biotin-dependent enzymes have now been described. These enzymes are acetyl CoA carboxylase, a pivotal enzyme in the synthesis of fatty acids; pyruvate carboxylase, which catalyzes the initial committed step in gluconeogenesis; propionyl CoA carboxylase, which catabolizes the branched-chain amino acids valine, isoleucine, methionine, and threonine, as well as the odd-chain fatty acids and the side chain of cholesterol; and β-methylcrotonyl CoA carboxylase, which catalyzes the catabolism of leucine. In addition, a heterogeneous group of multiple carboxylase deficiencies have recently been characterized in which the activities of at least three mitochondrial biotin-dependent carboxylases are diminished. The purpose of this review article is to delineate and compare the clinical, biochemical, and genetic features of these inherited metabolic disorders.