biotinidase

Biotinidase is an enzyme that cleaves biotin from biocytin and biotinylated proteins, allowing recycled free biotin to be reused in biotin-dependent carboxylases. It is encoded by the BTD gene and is active in various tissues, with significant function in biotin salvage.

Biotinidase deficiency is a genetic metabolic disorder inherited in an autosomal recessive pattern. Mutations in the BTD gene reduce or abolish enzyme activity, leading to impaired biotin recycling. Clinically, there are profound and partial forms, corresponding to the residual enzyme activity. Profound deficiency typically presents in infancy, while partial deficiency may become evident later in childhood or adulthood. Without treatment, affected individuals may develop seizures, hypotonia, developmental delay, vision or hearing problems, skin rashes (dermatitis), and hair loss (alopecia). Metabolic features can include metabolic acidosis and organic acid abnormalities due to impaired activity of biotin-dependent carboxylases.

Diagnosis relies on screening and confirmatory testing. Newborn screening programs often measure biotinidase activity in dried blood spots; a low activity result prompts confirmatory testing, including sequencing of the BTD gene. Early detection is important to prevent permanent neurologic damage.

Treatment is lifelong and consists of biotin supplementation. Doses are tailored to age and severity, commonly ranging from a few milligrams per day to higher amounts in older individuals. With timely treatment, many symptoms improve or stabilize, and normal development is possible. If untreated, the condition can lead to significant morbidity and, in rare cases, life-threatening outcomes.