Defects in biotin (Btn) metabolism

Biotin (Btn, vitamin B7, vitamin H, coenzyme R) is an essential cofactor for five biotin-dependent carboxylase enzymes, involved in the synthesis of fatty acids, isoleucine, valine and in gluconeogenesis. Thus, Btn is necessary for cell growth, fatty acid synthesis and the metabolism of fats and amino acids. Inherited metabolic disorders characterized by deficient activities of all five biotin dependent carboxylases are termed multiple carboxylase deficiencies. Two congenital defects in biotin metabolism leading to multiple carboxylase deficiency are known, holocarboxylase synthetase deficiency (MIM 609018) and biotinidase deficiency (MIM 253260). In both scenarios symptoms include ketolactic acidosis, organic aciduria, hyperammonemia, skin rashes, hypotonia, seizures, developmental delay, alopecia, and coma. As humans are auxotrophic for Btn, the micronutrient must be obtained from external soures such as intestinal microflora and dietary forms. Accordingly, severe malnutrition can also give rise to biotin deficiency and multiple carboxylase deficiency. Biotin deficiency can also be induced by the excessive consumption of raw egg white that contains the biotin-binding protein avidin. Holocarboxylase synthetase deficiency arises when all five biotin-dependent enzymes are not biotinylated leading to their reduced activities. The defective genes causing these conditions are described here. Biotinidase deficiency is caused by defects in the recycling of Btn. General symptoms include decreased appetite and growth, dermatitis and perosis. The defective genes causing these conditions are described here.

Summary from Reactome (R-HSA-3323169), read 2026-09-23.