Evaluation of biotinidase deficiency cases detected by newborn screening

Introduction:The biotinidase enzyme is involved in the recovery of biotin and conversion of biotin into its usable free form. Autosomal recessive biotinidase deficiency is defined as profound (<10%activity) and partial biotinidase deficiency (10-30%activity) according to serum biotinidase enzyme activity. The disease can cause dermatological and neurological symptoms, visual and hearing impairments. Measurement of biotinidase enzyme activity in serum / plasma and molecular analysis giveguidancein diagnosis.Objective:In thisstudy, ouraimwasto investigate the demographic, clinical and characteristic features of biotinidase deficiency cases detected by newborn screening programretrospectively.Patients and Methods:It was planned to examine the files of all biotinidase deficiency patients detected by newborn screening who were followed up in our clinic and whose first visit was until 30.06.2020, excludingpatients with normal biotinidase enzyme activity in their follow-up, and to record the demographic, family, clinical follow-up, laboratory and imaging data of the patients included in the study.SPSS v.21 program was used to analyze the data.Results:2178 patient files were examined and 76 patients whohad normal biotinidase enzyme activity during their follow-up were excluded from the study.2102 patients were included in the study,46.3% were female and 53.7% were male. Average age was 5.0 ± 4.7 years; median age at diagnosis was 22 days. Eastern Anatolia Region and Ağrı province were the most common regionsof the disease. Consanguineous marriage rate was 37.3%. Threshold values calculated by evaluating biotinidase activities for skin, hair, neurological findings and conjunctivitis symptoms were ≈14% and ≈5% for visual impairment. Partial deficiencies with enzyme activity above 25% were less symptomatic at high significance level compared to partial deficiencies with lower activity. Almost all of the skin andhair findings, hypotonia, hypertonia, seizures and conjunctivitis, 70% of hearing impairment and 25% of neuromotor growth retardation regressed with compliance to treatment. There was no improvement in visual impairment. The mean follow-up period of the patients was 2.7 ± 3.4 (median1, range0-25)years. The average quantitative biotinidase activity was 1.6 ± 0.8 nm/min/ml (N>2.6 nm/dk/ml) and the average percentage values were 18.2 ± 9.1%. According to the screening results of the Ministry of Health, the profound deficiency threshold value was found to be 26.17 MRU for 4the first screening result and 34.35 MRU for the second screening. With a similar calculation, the threshold value of 6.7% for high levels of C5OH in MSMS showed high sensitivity and specificity. According to the molecular analysis results; the most common mutations were p.R157H, p.D444H and p.T532M. When alleles were evaluated together, the most common mutationpairswere p.R157H-p.R157H, p.T532M-p.T532M and p.D444H-p.A171T.Conclusion:Biotinidase deficiency is an inherited metabolic disease and can be successfully managed with early diagnosis and compliance with treatment.A good understanding of the characteristics of the disease will help to direct treatment and reduce morbidity and mortality. Increasing studies on this subject, enlightening the genotype phenotype relationships of the patients will improve the knowledge about the disease..Keywords:Biotinidase deficiency, neonatal screening, metabolic diseases