Evaluati̇on of cli̇ni̇cal and genotypi̇c characteri̇sti̇cs i̇n pati̇ents wi̇th bi̇oti̇ni̇dase defi̇ci̇ency

Introduction: Biotinidase deficiency (BE) is a metabolic disease with autosomal recessive neurocutaneous findings with an incidence of 1:40000-60000 births in the world. According to serum biotinidase activity, it is defined as complete deficiency (<10% activity), partial deficiency (<10-30% activity) and carrier (<30-50%) activity. The number of mutations identified in this gene, which consists of 4 exons, increased day by day, and phenotype and genotype correlation could not be achieved. Objective: In our study, it was aimed to examine the demographic, clinical and characteristic features and genetic analyzes of patients followed up for biotinidase deficiency, and to evaluate the relationship between phenotype and genotype. Methods and Materials: Examining the files of all patients with biotinidase deficiency who applied to Akdeniz University Medical Faculty Pediatric Metabolism Polyclinic between January 2018 and September 2021, recording their demographic characteristics, clinical and laboratory data and genetic analysis, showing the relationship between biotinidase enzyme activities and variants, phenotype and It was planned to reveal the genotype relationship. Data IBM SPSS Statistics 18 © Copyright SPSS Inc. It was analyzed using the 1989, 2010 software. Results: Of the 107 patients whose files were examined, 60% were boys and 47% were girls. The mean age was calculated as 61.06±52.83 months. The most common region of the patients was the Mediterranean Region (33%) and Antalya (21%). Our consanguineous marriage rate is 35.5%. Biotinidase enzyme activity averages are 1.80±1.03 nmol/min/ml. 14% of the patients are in the complete deficiency, 46.7% in the partial deficiency, and 39.3% in the carrier group. Symptoms are present in 15.9% of the patients, 7.5% of the patients have skin and 6.5% hair findings, 4.7% of them have neuromotor developmental delay, 3.7% of them have convulsions. When the patients were grouped as complete deficiency, partial deficiency and carriers, the carriers with the lowest mean age were found to be 21.5 months. The history of consanguinity was found to be higher in the complete deficiency group with a rate of 66.7%. When 17 symptomatic patients were evaluated, no statistically significant results could be obtained. Mutation was detected in 83 of 107 patients. The most common mutation is 47% heterozygous p.D444H. Homozygous p.Q456H mutation was found in 62.5% in complete deficiency, heterozygous p.D444H mutation in partial deficiency, and homozygous p.D444H mutation in carrier group. Frame shift mutation was found only in Aegean and Mediterranean Regions. Conclusion: Neonatal screening programs provide early diagnosis and treatment in biotinidase deficiency, which is a metabolic disease. Although BTD enzyme activity is essential in the diagnosis, performing BTD gene analysis is important in supporting the diagnosis, following the patient in terms of complications, and determining the genotype-phenotype relationship. Keyword: biotinidase deficiency, hereditary metabolic disease, genotype-phenotype correlation