Biotinidase

Biotinidase deficiency is an autosomal recessive disorder that is caused by variants in the biotinidase gene (BTD). Individuals with profound biotinidase deficiency have less than 10% of mean normal serum biotinidase enzyme activity, while individuals with partial biotinidase deficiency have 10% to 30%. Biotinidase deficiency is included in most newborn screening programs. The estimated incidence of profound and partial deficiencies is 1 in 61,000 births.A newborn screen should be collected prior to transfusion since transfusion may mask the deficiency. 

Infants with profound biotinidase deficiency appear normal at birth but develop one or more of the following symptoms after the first few weeks of life: seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities such as alopecia, skin rash and candidiasis. 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. Children with partial biotinidase deficiency identified by newborn screening should remain asymptomatic if biotin therapy is instituted early and continuously maintained.

Newborns who have a positive screening test should have confirmatory testing for biotinidase deficiency.  The reference range for serum biotinidase activity is 3.5-13.8 U/L. 

Patients who are confirmed to have biotinidase deficiency will benefit form sequencing of the entire BTD gene to detect disease-causing variants. Family members should also be offered genetic testing. 

References

Biotinidase Deficiency, National Organization for Rare Disorders, rarediseases.org

Biotinidase Deficiency, Genetic and Rare Diseases Information Center, rarediseases.info.nih.gov

Tankeu AT, et al. Biotinidase deficiency: What have we learned in forty years? Mol Genet Metab. 2023 Apr;138(4):107560. doi: 10.1016/j.ymgme.2023.107560.