Newborn screening for biotidinase deficiency experience in Latvia

Background: Biotinidase deficiency (BD) is a rare, autosomal recessive inherited disease causing a defect in the biotin-releasingenzyme, leading to biotin shortage. BD newborn screening (NBS) allows early diagnosis and treatment, providing excellentprognosis.Case Study / Methods: We analysed NBS results from the Genetics Laboratory of the Children's Clinical University Hospital inRiga, from 01.07.2019 to 01.04.2022. Newborn dried blood spots (DBS) were collected between 48-72 h of life. If the first DBSvalue was below cut-off (biotinidase <100 nmol/min/dl), a second sample was requested, and if biotinidase activity was still below100, then a third one was acquired. If the level was below cut-off the third time, molecular testing of BTD gene was carried out.Results: A total of 48 512 initial screenings were performed, of which 586 (1.2%) were outside the reference range, the lowestlevel detected 42,61 nmol/min/dl. The second sample testing yielded 68 (0.14 %) samples below the cut-off value, the lowest leveldetected 51,52nmol/min/dl. Molecular BTD gene testing was performed in 6 patients due to repeatedly reduced biotinidaseactivity levels. Tree of them were homozygotes Asp424His/Asp424His, and one compound heterozygotes carryingAsp444His/Gln436His, one Asp424His/Arg79Cys and Asp424His/Ala271Val. Biotin - 5mg/day therapy was initiated in 2 patientswith partial BD with variants Asp424His/Gln436His and Asp424His/Arg79Cys. Partial biotinidase deficiency incidence 1: 24 256.Asymptomatic sibs were also tested for BTD gene in these two patients, the same variants were found, and treatment was startedwith Biotin 5mg/day.Conclusion / Discussion: The study revealed that if the third sample was requested, biotinidase activity in the third sample waswithin the normal range in most cases. Even if the reduction in biotinidase activity in the first and second sample was about 40%. Therefore, we have now changed the algorithm, and molecular testing for BTD gene is performed if the value is below the cut-offin the second sample