A retrospective study on biotinidase deficiency: analysis of the Eastern Anatolia region patient cohort.

ABTRACTThis study retrospectively reviews individuals diagnosed with biotinidase deficiency in Eastern Anatolia to analyze the genetic variants and their relationship with biotinidase activity levels. The research focuses on determining the percentage impact of different variants on enzyme activity. The study included 357 patients who presented to Erzurum City Hospital with symptoms of biotinidase deficiency between 2018 and 2023 and were referred to the medical genetics department. Biotinidase enzyme levels were determined using spectrophotometric and colorimetric techniques, while Sanger sequencing analyzed the four exons and intron boundaries of the BTD gene. In the analysis of 357 patients (181 boys, 176 girls), the most frequent variant was c.1270G > C | p.Asp424His. Biotinidase enzyme activity was above 30% in 97.3% of patients with a homozygous p.D424His mutation. The mutations that caused the most significant decrease in enzyme activity were c.410G > A p.Arg137His, c.38_delinsTCC p.Cys13phefs*36, and c.1535C > T p.Thr512Met. Hearing loss (4 patients) and optic atrophy (1 patient) were mainly observed in patients with the c.38_delinsTCC mutation (homozygous or heterozygous). Most patients were asymptomatic, and mild symptoms were effectively prevented with biotin treatment. This study provides a detailed analysis of genetic diversity and clinical presentation in biotinidase deficiency cases in Eastern Anatolia, demonstrating the efficacy of biotin treatment. It highlights the significant role of genetic variants in phenotypic diversity and the need for personalized treatment, calling for further genetic research to enhance understanding of variant diversity and its impact on enzyme activity.