Abstract

OBJECTIVE: We describe our 37-year experience of newborn screening for biotinidase deficiency.

PATIENTS AND METHODS: From January 1987 to December 2023, we screened 1,289,389 newborns. Newborn screening was performed using a quantitative evaluation of biotinidase activity on dried blood spots (DBS) collected within the first 72 hours of life. In case of a positive result, the second-tier test is performed. If abnormal values are confirmed, newborns are referred to a quantitative measurement of serum biotinidase activity and a clinical and molecular evaluation.

RESULTS: We screened 1,289,389 newborns and found 52 patients with profound or partial biotinidase deficiency (incidence 1:25,000). The D444H variant was detected in 58% of patients, mostly with partial biotinidase deficiency. The Q456H mutation was found in most patients (62%) with profound biotinidase deficiency. The complex allele A171T/D444H in cis configuration was observed in three patients (5.7%) affected from profound or partial biotinidase deficiency depending on the mutation presented in trans (in compound heterozygosity with the protective allele D444H in trans, in homozygosity and compound heterozygosity with the R211H mutation, respectively). All identified patients were treated and regularly followed up at our center. Biotin therapy was administered at 10 or 20 mg/day in patients with partial or profound biotinidase deficiency, respectively. On this treatment, all patients were asymptomatic on long-term follow-up. Moreover, no adverse effects were reported, even in patients treated for over 35 years.