Biotin-responsive multiple carboxylase deficiency (MCD): deficient biotinidase activity associated with renal loss of biotin.

Abstract

Biotin-responsive multiple carboxylase deficiencies (MCD) are inherited disorders characterized biochemically by the accumulation of a typical pattern of organic acids, caused by decreased activity of the three mitochondrial biotin-containing enzymes: propionyl CoA carboxylase (PCC., EC 6.4.1.3), 3-methylcrotonyl CoA carboxylase (MCC., EC 6.4.1.4) and pyruvate carboxylase (PC., EC 6.4.1.1). Clinically this disorder exists in at least two forms, namely an early-onset (neonatal) and a late-onset (juvenile) form. Both types of the disorder respond to high doses of biotin. In most instances, the neonatal form appears to be caused by deficient holocarboxylase synthetase activity due to an elevated K m for biotin (Burri et al., 1981), while in some patients with late-onset MCD the primary biochemical defect has recently been found to be a deficiency in the activity of biotinidase, the enzyme regenerating biotin from endogenous biocytin (Wolf et al., 1983).