Biotinidase deficiency is an inherited disorder in which the
vitamin,
biotin, is not recycled. Individuals with
biotinidase deficiency can develop neurological and cutaneous symptoms if they are not treated with
biotin.
Biotinidase deficiency screening has been incorporated into essentially all newborn screening programs in the United States and in many countries. We now report 140 known mutations in the
biotinidase gene (BTD) that cause
biotinidase deficiency. All types of mutations have been found to cause
biotinidase deficiency. Variants have been identified throughout the coding sequence. Essentially all the variants result in enzymatic activities with less than 10% of mean normal
enzyme activity (profound
biotinidase deficiency) with the exception of the c.1330G>C (p.D444H) mutation, which results in an
enzyme having 50% of mean normal serum activity. The putative three-dimensional structure of
biotinidase has been predicted by homology to that of nitrilases/
amidases. The effect of the various missense mutations can be predicted to affect various important sites within the structure of the
enzyme. This compilation of variants causing
biotinidase deficiency will be useful to clinical laboratories that are performing mutation analysis for confirmational testing when the enzymatic results are equivocal for children identified through newborn screening.