Metabolic disorders

Inherited metabolic disorders characterized by deficient activities of biotin-dependent carboxylases are termed multiple carboxylase deficiency. These include deficiencies in the enzymes holocarboxylase synthetaseor biotinidase. Holocarboxylase synthetase deficiencyprevents the body's cells from using biotin effectively, and thus interferes with multiple carboxylase reactions.[25]Biochemical and clinical manifestations include: ketolactic acidosis, organic aciduria, hyperammonemia, skin rash, feeding problems, hypotonia, seizures, developmental delay, alopecia, and coma.

Biotinidase deficiencyis not due to inadequate biotin, but rather to a deficiency in the enzymesthat process it. Biotinidasecatalyzes the cleavage of biotin from biocytin and biotinyl-peptides (the proteolytic degradation products of each holocarboxylase) and thereby recycles biotin. It is also important in freeing biotin from dietary protein-bound biotin.[25]General symptoms include decreased appetiteand growth. Dermatologic symptoms include dermatitis, alopecia, and achromotrichia(absence or loss of pigment in the hair).[26]Perosis(a shortening and thickening of bones) is seen in the skeleton. Fatty liver and kidney syndromeand hepatic steatosisalso can occur.[20]