Abstract

Two inherited defects affecting the coenzyme function of biotin are known: holocarboxylase synthetase (HCS) deficiency and biotinidase deficiency. Both lead to deficiency of all biotin-dependent carboxylases, i.e. to multiple carboxylase deficiency (MCD). In HCS deficiency, the binding of biotin to apocarboxylases is impaired. In biotinidase deficiency, biotin depletion ensues from the inability to recycle endogenous biotin and to utilise protein-bound biotin from the diet. As the carboxylases play an essential 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 organic aciduria and neurological symptoms. The clinical presentation is extremely variable in both disorders. Characteristic symptoms include metabolic acidosis, hypotonia, seizures, ataxia, impaired consciousness and cutaneous symptoms, such as skin rash and alopecia.