Abstract
INTRODUCTION: Biotinidase enzyme is responsible for recycling biotin which is essential for metabolic functions. Loss of function mutations in the BTD gene causes biotinidase deficiency (BTD). It is diagnosed by measuring biotinidase activity and it can lead to severe neurological symptoms. We aimed to evaluate biotinidase activity changes in patients with BTD over time. METHODS: 194 patients with BTD were enrolled. Clinical, laboratory and genetic data of the patients were retrospectively evaluated. Patients with enzyme activity below 10% of normal were diagnosed with profound BTD while patients with enzyme activity between 10% and 30% were diagnosed with partial BTD. RESULTS: 104 (53.6%) patients were male, most patients were diagnosed at screening (n = 183, 94.3%) and the mean age at the time of diagnosis for symptomatic patients was 82.7 ± 22.8 (range: 1-216) months. Two (1%) patients had profound BTD, 168 (86.6%) patients had partial BTD, and 24 (12.4%) patients had more than 30% of normal biotinidase activity. Overall, the last measured biotinidase activity levels were significantly higher than the initial measurements (p < 0.0001). This finding was valid for all subgroups classified according to birth week, birth weight, and consanguineous marriage status. The increase in enzyme rate over time was slower in children of consanguineous marriages compared to children who were not. DISCUSSION: This study showed that biotinidase activity increased in BTD patients over time and repeated measurements of biotinidase would be a better approach to evaluate BTD. In addition, consanguineous marriage may be a risk factor for a worse prognosis in BTD.