Acra Neurol Scand zyxwvutsrqponmlkj 1999: zyxwvutsrqpon 99: zyxwvutsrqponm 387-392 Prinred in UK. A l l righis reserved Copyright c Munhgaard zy 1999 zy ACTA NEUROLOGICA SCANDINAVICA ISSN 0001-6314 zyx Cerebrospinal fluid levels of biotin in various neurological disorders Anagnostouli M, Livaniou E, Nyalala JO, Evangelatos G, Zournas C, Ithakissios DS, Papageorgiou C. Cerebrospinal fluid levels of biotin in various neurological disorders. Acta Neurol Scand 1999: 99: 387-392. zyxwvu 0 Munksgaard 1999. Objectives - To analyse biotin concentrations in human cerebrospinal fluid (CSF) and serum from controls without evidence of nutritional or neurological disorders and patients with common neurological disorders. Patients and methods - Cerebrospinal fluid was obtained from patients by lumbar puncture, serum was prepared from freshly drawn whole blood and biotinidase in samples was inhibited before being analysed for biotin by radioligand assay. Results - Assay characteristics were within an acceptable range (intra-and interassay coefficient of variations were 8.8 and 12.0 respectively, recovery: 91-1 14% and sensitive, lowest standard concentration 15 ng/l). Significantly lower values for biotin were found in patients with multiple sclerosis (both CSF and serum) in comparison to the controls. Significantly reduced values for cerebrospinal fluid biotin were found in epileptics compared to controls, whereas, in serum the difference was approaching significance. No significant differences were observed in other groups of patients. Conclusion - There is a significant reduction in cerebrospinal fluid biotin in epileptics and patients with multiple sclerosis compared to controls. In epileptics this may be related to competition between biotin and anticonvulsants bearing carbamide ring for absorption. Reduction of biotin levels in patients with multiple sclerosis could be attributed to intestinal malabsorption caused by the underlying disease or a biotin-binding immunoglobulin which may be involved in multiple sclerosis pathogenesis. Biotin is one of the less well known water-soluble vitamins of the B-complex group since acquired deficiency of this vitamin is rare in man. This is mainly due to its widespread occurrence in many different foodstuffs as well as its requirement in only trace amounts compared to other essential nutrients (1, 2). This compound functions as the prosthetic group of the 4 biotin-dependent carbox- ylases involved in the fixation of carbon dioxide in the human brain as well as other tissues (3, 4): propionyl CoA carboxylase (PCC, EC 6.4.1.3), acetyl CoA carboxylase (ACC, EC 6.4.1.2), 3- methylcrotonyl CoA carboxylase (MCC, 6.4.1.4) and pyruvate carboxylase (PC, EC 6.4.1.1). The 4 carboxylases play a central role in vitally important metabolic pathways, i.e. glyconeogenesis (PC), fatty acid synthesis (ACC), catabolism of several branched-chain amino acids (PCC, MCC) and zyxwv M. Anagnostouli', E. Livaniou', J. 0. Nyalala', G. Evangelatos', C. Zournas', zyx D. S. Ithakissios', C. Papageorgiou' 'Research Laboratory. Department of Neurology of Medical School, Athens National University. 'Radioimmunochemistry Lab , Institute of Radioisotopes/Radiodiagnostic Products, NCSR "Demokritos", Aghia Paraskevi Attikis. 153 10, Greece :ey words: biotin: cerebrospinal fluid, serum; ieurological disorder 11 Maria Anagnostouli, Department of Neurology. dedicat School, Athens National University. Eginition lospitat. Vasilissis Sofias Ave 72-74, 11S28. Athens, hece iccepted for publication January 18, 1999 metabolism of some neurotransmitters, aspartate and glutamate (5). The carboxylases are syn- thesized as essentially inactive apocarboxylases lacking biotin. The enzymatically active holocar- boxylases are formed within the cells by the enzyme holocarboxylase synthetase which binds biotin covalently to a lysyl-s-amino group of the apoc- arboxylases. The overall reaction catalysed by carboxylases requires the presence of metal ions (M2+), since the biotin-containing enzymes are metal ion dependent (6). Humans cannot synthe- size biotin and therefore, derive the vitamin from dietary sources and possibly from the synthetic activity of the gastrointestinal microflora or from the normal turnover of the holocarboxylases in cells, which are degraded proteolytically to biocy- tin, i.e. biotin bound to a lysyl-residue, or to short biotinyl-peptides (7). Biotinidase is the only 387