Retrospective evaluation of 901 patients diagnosed with biotinidase deficiency: 30 years of experience

Biotinidase deficiency is an inherited metabolic disease that is often symptomatic in the second month of life and can be treated with biotin. It is aimed to reduce long-term mortality and morbidity by detecting it in the asymptomatic period with newborn screening. In this study, patients followed up with biotinidase deficiency in one of the most experienced metabolic disease centers in our country were examined retrospectively, and the phenotypic and genotypic characteristics of the patients were determined. 901 patients diagnosed with symptomatic, family screening or newborn screening between 1990 and 2020 were included in the study. 733 patients were identified by newborn screening, 135 patients by family screening, and 33 symptomatic patients. 641 patients were diagnosed with partial and 260 patients with profound biotinidase deficiency. Consanguinity rate was 34.9%. The most common findings in symptomatic patients were seizures, alopecia, and respiratory problems. There was no increase in the frequency of seizures, hearing loss, visual impairment and congenital malformations in patients who diagnosed as asymptomatic with newborn screening compared to the normal population. According to the results of the National Neonatal Screening Program, the cut-off value for severe deficiency was 21.5 MRU in the blood sample taken within the first 48 hours, and 33.9 MRU in the second sample. The most common mutation in symptomatic patients was c.98_104delGCGGCTGinsTCC, and the most common mutation in patients with severe deficiency was c.470G>A (p.Arg157His). The mean enzyme activity of patients homozygous for c.1330G>C (p.Asp444His) was 28.7%. Since this study reflects the general characteristics and follow-ups of patients diagnosed with biotinidase deficiency in our country, it was thought that it would be a source for improving the diagnosis and follow-up processes of patients based on this study.