Biotin-Responsive Multiple Carboxylase Deficiency

Abstract

Two inherited defects in biotin metabolism are known: holocarboxylase synthetase (HCS) deficiency and biotinidase deficiency. Both lead to multiple carboxylase deficiency (MCD). In HCS deficiency, the formation of holocarboxylases is impaired. In biotinidase deficiency, biotin depletion ensues from the inability to recycle endogenous biotin and to utilize protein-bound biotin from the diet. As the carboxylases play an important role in the catabolism of several amino acids, in gluconeogenesis and in fatty-acid synthesis, their deficiency provokes multiple, life-threatening metabolic derangements, eliciting characteristic organicaciduria and neurologic symptoms. The clinical presentation is extremely variable in both disorders. Characteristic manifestations of MCD are metabolic acidosis, hypotonia, seizures, ataxia, impaired consciousness and cutaneous symptoms, such as skin rash and alopecia. Both disorders respond dramatically to oral therapy with pharmacological doses of biotin. Acquired biotin deficiency, which also causes MCD, is extremely rare.