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Biotin accounts for less than half of all biotin and biotin metabolites in the cerebrospinal fluid of children^1,2,3

¹ From the Departments of Biochemistry and Molecular Biology (AB, SLS, and DMM), Pathology (DAE), and Pediatrics (DAE and DMM), University of Arkansas for Medical Sciences, Little Rock, AR

Background: Biotin is likely transported into cerebral spinal fluid (CSF) via one or more specific transporters. Concentrations of biotin in CSF measured by using modern analytic techniques that are specific for biotin and biotin metabolites have not previously been reported.

Objectives: We aimed to accurately measure the concentration of biotin and major biotin metabolites, biotin sulfoxide (BSO) and bisnorbiotin (BNB), in the CSF of children.

Design: Concentrations of biotin were determined initially as total avidin-binding substances (TABS) in CSF obtained by lumbar puncture from 55 children. Biotin, BSO, and BNB were quantitated by HPLC and an avidin-binding assay in CSF samples from a subset of 11 children.

Results: Concentrations of TABS in CSF averaged 1.6 nmol/L with substantial variability (SD = 1.3 nmol/L). CSF concentrations of biotin and biotin analogs varied widely, but substantial amounts of BSO were detected in every sample. Biotin accounted for 42 ± 16%, BSO for 41 ± 12%, and BNB for 8 ± 14% of the total. It was surprising that the molar sum of biotin, BSO, and BNB on average was >200-fold the TABS concentrations from the same CSF sample. Using several analytic approaches, we found no masking of detection, nor did we find degradation of biotin or BSO. Gel electrophoresis and streptavidin Western blot detected several biotinylated proteins in CSF.

Conclusions: Biotin appears to be bound to protein covalently, reversibly, or both, and this binding likely accounts for the increase in detectable biotin after HPLC. Protein-bound biotin may play an important role in biotin nutriture of the brain.