Objective: Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder. Biotin plays an important role as a cofactor of carboxylases. BD is categorized into two groups as profound and partial deficiency based on serum quantitative biotinidase enzyme activity (BA). Clinical manifestations are highly variable, ranging from severe metabolic acidosis to asymptomatic.

Methods: Patients who were referred to the pediatric metabolism department due to the suspicion of BD are retrospectively retrieved. This study was conducted between 2019 to 2021 at Cengiz Gökçek Children’s Hospital. The values of quantitative BA, below 30% were defined as deficiency, 10-30% were defined as partial deficiency (PBD), and below 10% were defined as profound deficiency (PFBD). Molecular analysis was performed on the patients. Quantitative analysis of the BA and BTD genes supported the diagnosis. Patients who were misdiagnosed with BD were classified as a false-positive group.

Results: A total of 255 patient files were retrospectively evaluated. 211 patients were included. The median age at presentation of the patients was 27±26,2 days (range: 10-240). 48.3% (n=102) patients in the BD group, and 51.7 % (n=109) patients in the false-positive group. Consanguinity was significantly higher in the BD group (p=0.002). The rate of patients with normal quantitative BA was 54.5% (n=115), PBD was 36.5% (n=77) and PFBD was 9% (n=19). For a variety of reasons, BTD gene analysis was carried out in 79.6% (n=168) of patients. 35.1% (n=59) of them were homozygous mutations, 13.1% (n=22) were compound heterozygous mutations, 40.5% were (n=68) heterozygous mutations, and 11.3% (n=19) were normal. Genetic analysis was consistent with BD in 26.8% (n=25/93) of patients with normal quantitative BA.

Conclusion: BA measurement may be affected by technical reasons. Because sensitivity and specificity of quantitative BA measurement methods are still controversial and inconsistent, confirmation of results by molecular analysis may reduce the risk of misdiagnosis.

Keywords: Biotinidase deficiency, biotin, newborn screening