Clinical Information

Biotinidase deficiency is an autosomal recessive disorder caused by disease-causing variants in the BTD gene. Age of onset and clinical phenotype vary among individuals depending on the amount of residual biotinidase activity.

Untreated profound biotinidase deficiency typically manifests within the first decade of life as seizures, ataxia, developmental delay, hypotonia, sensorineural hearing loss, vision problems, skin rash, and alopecia. Partial biotinidase deficiency is associated with a milder clinical presentation and may include cutaneous symptoms without neurologic involvement. Certain organic acidurias, such as holocarboxylase synthase deficiency, isolated carboxylase synthase deficiency, and 3-methylcrotonylglycinuria, present similarly to biotinidase deficiency. Serum biotinidase levels can help rule out these disorders.

Treatment with biotin is successful in preventing the clinical features associated with biotinidase deficiency. In symptomatic patients, treatment will reverse many of the clinical features except developmental delay, vision, and hearing complications. As a result, biotinidase deficiency is included in most newborn screening programs. This enables early identification and treatment of presymptomatic patients.

Molecular tests are useful for confirmation of diagnosis or carrier testing. When biotinidase enzyme activity is deficient, sequencing of the entire BTD gene (BTD / Biotinidase Deficiency, BTD Gene Sequencing with Deletion/Duplication, Varies) allows for detection of disease-causing variants in affected patients. While genotype-phenotype correlations are not well established, it appears that certain genetic variants are associated with profound biotinidase deficiency, while others are associated with partial deficiency.