Skip to main content
SpringerLink
Log in

Erniedrigung des Biotins als möglicher Faktor im Wirkmechanismus von Antiepileptika

Reduction of biotin level as a possible factor in the mode of action of anticonvulsants

  • Published:
Archiv für Psychiatrie und Nervenkrankheiten Aims and scope Submit manuscript

Summary

Of 117 patients treated with anticonvulsants reduced plasma biotin levels were found in over 80% of cases. Significant negative correlations with the average daily dose and the total amount of anticonvulsants as well as with the plasma phenytoin level were also evident. It is proposed that the lowering of biotin—which is a co-factor of the carboxylating enzyme system—is an important mechanism in mode of action of anticonvulsants. Reduced biotin levels possibly lead to an accumulation of carbon dioxide or a diminution of aspartate in brain tissue. Low biotin levels may also be the cause of some well known side effects of anticonvulsants such as cerebellar disturbances and dermatitis. In comparison to the other epileptics the patients with cerebellar symptoms showed significantly lowered plasma biotin levels.

Zusammenfassung

Bei über 80% von 117 antikonvulsiv behandelten Patienten wurde eine Erniedrigung des Biotin-Spiegels im Plasma gefunden. Signifikante negative Korrelationen zeigten sich zur durchschnittlichen Tagesdosis und zur Gesamtmenge der eingenommenen Antiepileptika sowie zum Diphenylhydantoin-Spiegel im Plasma. Es erscheint möglich, daß die Verminderung des in carboxylierenden Enzymen vorhandenen Biotins ein wesentlicher Faktor im Wirkmechanismus von Antiepileptika sein könnte; in Frage kämen hierbei in erster Linie eine Akkumulation von CO2 oder eine Erniedrigung des Aspartats im Hirngewebe. Darüber hinaus sind einige bekannte Nebenwirkungen von Antikonvulsiva wie zerebelläre Störungen und Dermatitiden eventuell durch die Senkung des Biotin-Spiegels bedingt. In unserem Krankengut waren die Biotin-Spiegel der Patienten mit zerebellären Störungen signifikant niedriger als die der übrigen Epileptiker.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literatur

  1. Bartlett K, Gompertz D (1976) Combined carboxylase defect: biotin-responsiveness in cultered fibroblasts. Lancet II:804

    Google Scholar 

  2. Baugh CM, Malone JH, Butterworth CE (1968) Human biotin deficiency. A case history of biotin deficiency induced by raw egg consumption in a cirrhotic patient. Am J Clin Nutr 21:173–182

    Google Scholar 

  3. Bonjour JP (1977) Biotin in man's nutrition and therapy — a review. Int J Vit Nutr Res 47:107–118

    Google Scholar 

  4. Bonjour JP (1980) Vitamins and alcoholism. IV. Thiamin Int J Vit Nutr Res 50:321–338

    Google Scholar 

  5. Bonjour JP (1980) Vitamins and alcoholism. V. Riboflavin, VI. Niacin, VII. Pantothenic acid, and VIII. Biotin. Int J Vit Nutr Res 50:425–440

    Google Scholar 

  6. Bonjour JP (1981) Biotin-dependent enzymes in inborn errors of metabolism in humans. Wld Rev Nutr Diet: in press

  7. Caspers H, Speckmann EJ (1969) DC potential shifts in paroxysmal states. In: Jasper HH, Ward AA, Pope A (eds) Basic mechanisms of the epilepsies. Little, Brown and Co, Boston, pp 375–388

    Google Scholar 

  8. Charles BM, Hosking G, Green A, Pollit R, Bartlett K, Taitz LS (1979) Biotin-responsive alopecia and developmental regression. Lancet II:118–120

    Google Scholar 

  9. Cowan MJ, Wara DW, Packman S, Ammann AJ, Yoshino M, Sweetman L, Nyhan WL (1979) Multiple biotin-dependent carboxylase deficiencies associated with defects in T-cell and B-cell immunity. Lancet II:115–118

    Google Scholar 

  10. Frigg M, Brubacher G (1976) Biotin deficiency in chicks fed a wheat-based diet. Int J Vit Nutr Res 46:314–321

    Google Scholar 

  11. Glaser GH (1972) Diphenylhydantoin toxicity. In: Woodbury DN, Penry JK, Schmidt RP (eds) Antiepileptic drugs. Raven, New York, pp 219–226

    Google Scholar 

  12. Gompertz D, Draffan GH, Watts LJ, Hull D (1971) Biotin-responsive β-methylcrotonylglycinuria. Lancet II:22–24

    Google Scholar 

  13. Krause KH, Prager P, Schmidt-Gayk H, Ritz E (1977) Diagnostik der Osteopathia antiepileptica im Erwachsenenalter. Dtsch Med Wochenschr 102:1872–1877

    Google Scholar 

  14. Leevy CM, Baker H, ten Hove W, Frank O, Cherrick GR (1965) B-complex vitamins in liver disease of the alcoholic. Am J Clin Nutr 16:339–346

    Google Scholar 

  15. Lynen F (1966) Die Stoffwechselfunktion des Biotins. In: von Kress H, Blum K-U (Hrsg) B-Vitamine. Klinische und physiologisch-chemische Probleme. Schattauer, Stuttgart, S 3–21

    Google Scholar 

  16. Mehregan U, Krause K-H, Prager P (1979) Zur Häufigkeit der Osteopathia antiepileptica in Abhängigkeit von Behandlungsdauer und Medikamentendosis. Arch Psychiat Nervenkr 226:299–310

    Google Scholar 

  17. Mock DM, de Lorimer AA, Liebmann WM, Sweetman L, Baker H (1981) Biotin deficiency: an unusual complication of parenteral alimentation. N Engl J Med 304:820–823

    Google Scholar 

  18. Patsalos PN, Lascelles PT (1981) Changes in regional brain levels of amino acid putative neurotransmitters after prolonged treatment with the anticonvulsant drugs diphenylhydantoin, phenobarbitone, sodium valproate, ethosuximide, and sulthiame in the rat. J Neurochem 36:688–695

    Google Scholar 

  19. Reynolds EH (1976) Folate and epilepsy. In: Bradford HF, Marsden CD (eds) Biochemistry and neurology. Academic Press, London New York San Francisco, pp 247–252

    Google Scholar 

  20. Richens A, Rowe DJF (1970) Disturbance of calcium metabolism by anticonvulsant drugs. Br Med J IV:73–76

    Google Scholar 

  21. Roth K, Cohn R, Yandrasitz J, Preti G, Dodd P, Segal S (1976) Beta-methylcrotonic aciduria associated with lactic acidosis. J Pediat 88:229–235

    Google Scholar 

  22. Sander JE, Malamud N, Cowan MJ, Packman S, Amman AJ, Wera DW (1980) Intermittent ataxia and immunodeficiency with multiple carboxylase deficiencies: a biotin-responsive disorder. Ann Neurol 8:544–547

    Google Scholar 

  23. Saunders M, Sweetman L, Robinson B, Roth K, Cohn R, Gravel AR (1979) Biotin-responsive organicaciduria. Multiple carboxylase defects and complementation studies with propionicacidemia in cultured fibroblasts. J Clin Invest 64:1695–1702

    Google Scholar 

  24. Scott D (1958) Clinical biotin deficiency (“egg white injury”). Report of a case with some remarks on serum cholesterol. Acta Med Scand 162:69–70

    Google Scholar 

  25. Straughan DW (1976) Amino acid transmitters: Pharmacological and electrophysiological aspects: In: Bradford HF, Marsden CD (eds) Biochemistry and neurology. Academic Press, London New York San Francisco, pp 213–231

    Google Scholar 

  26. Sweetman L, Bates SP, Hull D, Nyhan WL (1977) Propionyl-CoA carboxylase deficiency in a patient with biotin-responsive 3-methylcrotonylglycinuria. Pediat Res 11:1144–1147

    Google Scholar 

  27. Sweetman L, Suhr L, Nyhan WL (1979) Deficiencies of propionyl-CoA and 3-methylcrotonyl-CoA carboxylases in a patient with a dietary deficiency of biotin. Clin Res 27: 118 A

  28. Sydenstricker VP, Singal SA, Briggs AP, de Vaughn NM, Isbell H (1942) Observations on the “egg white injury” in man. JAMA 118:1199–1200

    Google Scholar 

  29. Tanaka K (1981) New light on biotin deficiency. N Engl J Med 304:839–840

    Google Scholar 

  30. Thoene J, Baker H, Yoshino M, Sweetman L (1981) Biotin-responsive carboxylase deficiency associated with subnormal plasma and urinary biotin. N Engl J Med 304:817–820

    Google Scholar 

  31. Weyler W, Sweetman L, Maggio DC, Nyhan WL (1977) Deficiency of propionyl-CoA carboxylase and methyl-crotonyl-CoA carboxylase in a patient with methylcrotonylglycinuria. Clin Chem Acta 76:321–328

    Google Scholar 

  32. Williams RH (1943) Clinical biotin deficiency. N Engl J Med 228:247–252

    Google Scholar 

  33. Woodbury DM (1980) Carbonic anhydrase inhibitors. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: mechanisms of action. Raven, New York, pp 617–633

    Google Scholar 

  34. Woodbury DM, Karler R (1960) The role of carbon dioxide in the nervous system. Anesthesiology 21:686–703

    Google Scholar 

  35. Woodbury DM, Rollins LT, Gardner MD, Hirschi WL, Hogan JR, Rallison ML, Tanner GS, Brodie DA (1958) Effects of carbon dioxide on brain excitability and electrolytes. Am J Physiol 192:79–90

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung für Epileptologie und klinische Neurophysiologie der Neurologischen Universitätsklinik Heidelberg, Voßstraße 2, D-6900, Heidelberg, Bundesrepublik Deutschland

    Klaus -Henning Krause, Peter Berlit & Jean -Pierre Bonjour

  2. Abteilung für Vitamin- und Ernährungsforschung, F. Hoffmann-La Roche & Co., CH-4002, Basel, Schweiz

    Klaus -Henning Krause, Peter Berlit & Jean -Pierre Bonjour

Authors
  1. Klaus -Henning Krause
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Berlit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean -Pierre Bonjour
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krause, K.H., Berlit, P. & Bonjour, J.P. Erniedrigung des Biotins als möglicher Faktor im Wirkmechanismus von Antiepileptika. Arch Psychiatr Nervenkr 231, 141–148 (1982). https://doi.org/10.1007/BF00343835

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00343835

Key words

Schlüsselwörter

Search

Navigation