Newborn screening for biotinidase deficiency (BD) provides prevention of neurological sequelae in patients with low residual enzyme activity by early treatment with oral biotin substitution. Screening 1.1 million newborns in Austria and consecutive family studies led to the identification of 21 patients with profound BD (residual activity <10%) (incidence: 1:59,800) and to 12 patients with partial BD (residual activity 10%-30%) (incidence 1:89,700). Application of an HPLC assay using the natural substrate biocytin allowed exact quantification of extremely low residual biotinidase activities and thus subdivision of patients with profound BD into a group with a residual activity 0%-1% of normal activity (n = 5) and >1%-<10% (n = 16) respectively. Evaluation of clinical and neuropsychological outcome showed that only patients with a biotinidase activity < 1% (n = 3/5) exhibited characteristic clinical symptoms within the first weeks of life, while five patients with a residual activity of 1.2%-4.6% did not develop clinical symptoms even when not treated until 3.5 21 years. In all patients with residual activity <10% and biotin substitution within the first weeks of life, neuropsychological outcome was normal, while abnormal in three out of five patients tested for IQ and treated after the age of 3.5 years. In five out of nine patients with poor compliance or delayed or no treatment, visual and brainstem auditory evoked potentials were measured and were within age-related normal values. All patients with partial BD available for follow-up remained clinically and neuropsychologically asymptomatic without treatment at ages 2.5 10 years.

Conclusion: The incidence of biotinidase deficiency in Austria is comparable to other European countries. Subdivision of the group of patients with profound biotinidase deficiency suggests that only patients with residual activities < 1% are prone to develop clinical symptoms early in life, while patients with residual activities >1% may remain asymptomatic even without treatment, as do patients with partial deficiency. Moderate mental retardation might represent a possible manifestation of cerebral dysfunction in patients with profound biotinidase deficiency.