If untreated, young children with profound biotinidase deficiency usually exhibit neurologic abnormalities including seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities (e.g., alopecia, skin rash, candidiasis). Older children and adolescents with profound biotinidase deficiency often exhibit motor limb weakness, spastic paresis, and decreased visual acuity. Once vision problems, hearing loss, and developmental delay occur, they are usually irreversible, even with biotin therapy. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress.
Individuals with profound biotinidase deficiency have less than 10% of mean normal serum biotinidase enzyme activity. Individuals with partial biotinidase deficiency have 10%-30% of mean normal serum biotinidase enzyme activity. Both profound and partial biotinidase deficiency are usually identified by newborn screening in states where such screening is offered. Molecular genetic testing of BTD, the only gene known to be associated with biotinidase deficiency, is clinically available.
Biotinidase deficiency is inherited in an autosomal recessive manner. With each pregnancy, a couple who has had one affected child has a 25% chance of having an affected child, a 50% chance of having a child who is an asymptomatic carrier, and a 25% chance of having an unaffected child who is not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.