Evaluation of 700 patients referred with a preliminary diagnosis of biotinidase deficiency by the national newborn metabolic screening program: a single-center experience.

OBJECTIVES: This study aimed to investigate the clinical, demographic and laboratory characteristics of the patients referred with a preliminary diagnosis of biotinidase deficiency through the national newborn metabolic screening program. We also attempted to determine the cut-off level of the fluorometric method used for screening biotinidase deficiency by the Ministry of Health.

METHODS: A total of 700 subjects who were referred to the Pediatric Metabolism Outpatient Clinic with a preliminary diagnosis of biotinidase deficiency through the national newborn metabolic screening program were retrospectively evaluated. Patients detected by family screening were excluded. Biotinidase enzyme activity was assessed and BTD gene analysis was performed in all patients.

RESULTS: Of 700 subjects who were referred by the screening program, 284 (40.5 %) had biotinidase deficiency (BD). The enzyme activity was 0-10, 10-30 and >30 % in 39 (5.5 %), 245 (35 %) and 416 (59.5 %) patients, respectively. The BD was partial in majority of patients (86.2 %). The cut-off level was 59.5 MRU for partial BD and 50.5 MRU for profound BD. The most common mutation detected was p.Arg157His (c.470G>A) among patients with profound BD, and p.D444H (c.1330G>C) among patients with partial BD.

CONCLUSIONS: Treatment should be initiated promptly in patients who are referred by the newborn screening program. Any mean activity under 59.5 MRU should be considered partial BD, while less than 50.5 MRU should be considered profound BD. It should be kept in mind that clinical manifestations may develop both in profound and partial BD.