Newborn screening for biotinidase deficiency: A 6-year single centre experience

Background: Newborn blood spot screening involves taking a blood sample to test for rare but serious health conditions. Vitamin deficiency can lead to a variety of health problems but early diagnosis enables early treatment and improves the prognosis and quality of life. In VI/2016, the Czech Republic's nationwide newborn screening was expanded for biotinidase deficiency, the most common inherited disorder of vitamin metabolism. Children with biotinidase deficiency identified by newborn screening may remain asymptomatic if biotin therapy is instituted early and continuously lifelong.

Methods: The newborn blood spots were collected between 48 to 72 hours after birth. Biotinidase activity was measured in dry blood spots by fluorometric assay and in serum by a colourimetric assay, respectively. The BTD gene was analysed by Sanger sequencing of PCR products of all coding exons.

Results: Samples from 477,825 newborns were analysed between July 2016 and May 2022. The recall rate was 0.028%. Profound biotinidase deficiency was confirmed in one newborn corresponding to a screening prevalence (P) of 1:480,000 and partial biotinidase deficiency was diagnosed in 45 cases (P=1:11,000). In patients with partial biotinidase deficiency, the mean biotinidase activity was 1.5±0.3 nmol/min/mL and the most common mutations were c.1330GC (50%) and c.1368AC (14%). All children are well on vitamin supplementation.

Conclusion: Newborn screening is an effective approach for presymptomatic detection of serious rare diseases. After expansion, the Czech Republic neonatal screening programme can detect a total of 37 inherited metabolic disorders including biotinidase deficiency.

Acknowledgement: Supported by MH CZ – DRO VFN64165.