Objectives: To study the clinical profile of children with biotinidase deficiency and their response to oral biotin.

Methods: Twenty-six consecutive patients with biotinidase deficiency diagnosed from September 2004-November 2013 were retrospectively reviewed. Initiation of biotin treatment was considered early (<6 months) and late (>6 months of age); responses were compared.

Results: Mean age at symptom-onset was 7.7 months (10 days-48 months). Developmental delay (65%), neuroregression (58%), seizures (81%), skin changes (65%), scanty hair (69%) and characteristic rash (31%) were noted at presentation. Generalized tonic-clonic seizures were (61.5%) preponderant. Microcephaly was seen in 35% and hypotonia in 65%. One child had macrocephaly. Perinatal-period was normal in 80%; one child had parental consanguinity. Common electroencephalography abnormalities were generalized spikes/spike-wave-complexes (31%), burst-suppression (15%), focal slowing (11%) and hypsarrhythmia (3%). Common magnetic-resonance-imaging abnormalities were diffuse cortical atrophy (31%), delayed myelination (8%) and non-specific white-matter hyperintensities (8%). Mean serum biotinidase level was 2.28 nmol/min/ml (range 0.08-5 nmol/min/ml). Oral biotin 10-20 mg/day was initiated in all patients; 50% were in early-treatment group. Mean follow-up period was 33.5 months. One patient was vegetative at 9 years of age and two patients died; 77% patients symptomatic relief following biotin therapy. Neurological sequelae noted were intellectual impairment, developmental delay, seizures, hyperactivity and vision-hearing impairments. Poorer seizure control (70% vs 85%), developmental delay (62% vs 70%) and hyperactivity (77% vs 92%) were noted in late vs early-treatment groups respectively.

Conclusion: Early recognition and prompt initiation of life-long biotin therapy helps in early seizure control and improved neurological outcomes.