Skip to main content
SpringerLink
Log in

Hyperaminoacidemia in epileptic children treated with valproic acid

  • Original Papers
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Serum amino acids were determined in 22 epileptic children treated with valproic acid. This treatment caused hypocarnitinemia in all, and hyperammonemia in 16. Regardless of the blood ammonia levels, values for glutamic acid, arginine, glycine, serine and alanine were higher than those of normal controls, while aspartic acid and ornithine were lower. These findings suggest that valproate causes intramitochondrial dysfunction of the urea cycle.

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

References

  1. Baetlet K (1977) Sodium valproate and hyperglycinaemia. Lancet II:716

    Google Scholar 

  2. Batalden PB, VanDyne BJ, Cloyd J (1979) Pancreatitis associated with valproic acid therapy. Pediatrics 8:282–284

    Google Scholar 

  3. Becker CM, Harris RA (1983) Influence of valproic acid on hepatic carbohydrate and lipid metabolism. Arch Biochem Biophys 223:381–392

    Google Scholar 

  4. Bohan TP, Millington DS, Ros CR, Yergey AL, Liberato DJ (1984) Valproylcarnitine: a novel metabolite of valproic acid. Ann Neurol 16:394

    Google Scholar 

  5. Castro-Gago M, Otero S, Novo I, Rodrigo-Saez E, Rozas I, Rodriguez-Segade S (1988) Deficiencia de carnitina asociada a hiperamoniemia en niños tratados con ácido valproico. Rev Esp Epilepsia 3:169–172

    Google Scholar 

  6. Committee on Drugs (1982) Valproic acid: benefits and risk. Pediatrics 70:316–319

    Google Scholar 

  7. Coude FX, Rabier D, Cathelineau L, Grimber G, Parvy P, Kamoun PP (1981) A mechanism for valproate-induced hyperammonaemia. Pediatr Res 15:974–975

    Google Scholar 

  8. Coulter DL, Allen RJ (1980) Pancreatitis associated with valproic acid therapy for epilepsy. Ann Neurol 7:92

    Google Scholar 

  9. Coulter DL, Allen RJ (1981) Hyperammonaemia with valproic acid therapy. J Pediatr 99:317–319

    Google Scholar 

  10. Coulter DL, Wu H, Allen RJ (1980) Valproic acid therapy in childhood epilepsy. JAMA 244:785–788

    Google Scholar 

  11. Gerber N, Dickinson RG, Harland RC, Lynn RK, Houghton D, Antoniast JI, Schimschock JC (1979) Reye-like syndrome associated with valproic acid therapy. J Pediatr 95:142–144

    Google Scholar 

  12. Hjelm M, Oberholzer V, Seakins J, Thomas S, Kay JDS (1986) Valproate-induced inhibition of urea synthesis and hyperammonaemia in healthy subjects. Lancet II:859

    Google Scholar 

  13. Iinuma K, Hayasaka K, Naisawa K, Tada K, Hori K (1988) Hyperamino-acidaemia and hyperammonaemia in epileptic children treated with valpric acid. Eur J Pediatr 148:267–269

    Google Scholar 

  14. Jaeken J, Corbeel L, Casaer P, Carchon H, Eggermont E, Eckels R (1977) Dipropylacetate (valproate) and glycine metabolism. Lancet I:617

    Google Scholar 

  15. Laub MC, Paetske-Brunner I, Jaeger G (1986) Serum carnitine during valproic acid therapy. Epilepsia 27:559–562

    Google Scholar 

  16. Michell ME (1978) Carnitine metabolism in human subjects. I. Normal metabolism. Am J Clin Nutr 31:293–299

    Google Scholar 

  17. Ohtani Y, Endo F, Matsuda I (1982) Carnitine deficiency and hyperammonaemia associated with valproic acid therapy. J Pediatr 101:782–785

    Google Scholar 

  18. Rozas I, Camiña MF, Paz JM, Castro-Gago M, Alonso C, Rodriguez-Segade S (1990) Effects of acute valproate administration on carnitine metabolism in mouse serum and tissues. Biochem Pharmacol 39:181–185

    Google Scholar 

  19. Sackellares JC, Lee SI, Dreifus FE (1979) Stupor following administration of valproic acid to patients receiving antiepileptic drugs. Epilepsia 20:697–701

    Google Scholar 

  20. Thurston JH, Carrol JE, Hauhart RE, Schiro JA (1985) Single therapeutic dose of valproate affects liver carbohydrate, fat, adenylate, amino-acid, coenzyme A, and carnitine metabolism in infant mice: possible clinical significance. Life Sci 36:1643–1651

    Google Scholar 

  21. Turnbull DM, Dick DJ, Wilson L, Sherratt HSA, Alberti KGMM (1986) Valproate causes metabolic disturbance in normal man. J Neurol Neurosurg Psychiatry 49:405–410

    Google Scholar 

  22. Ware S, Millawako-Sadler GH (1980) Acute liver disease associated with sodium valproate. Lancet II:1110–1111

    Google Scholar 

  23. Williams CA, Tiefenbach S, McReynolds JW (1984) Valproic acid induced hyperammonaemia in mentally retarded adults. Neurology 34:550–553

    Google Scholar 

  24. Yoshimoto T, Harima Y (1984) Follow-up of plasma ammonia levels in patients treated with valproic acid (VPA). Brain Dev 6:206

    Google Scholar 

  25. Young RSK, Bergman I, Gang DL, Richardson EP (1980) Fatal Reye-like syndrome associated with valproic acid therapy. Ann Neurol 7:389

    Google Scholar 

  26. Zimmerman HJ, Ishak KG (1982) Valproate-induced hepatic injury: analysis of 23 cases. Hepatology 5:591–597

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Pediatria, Servicio de Neuropediatria, Hospital Clinico Universitario, Universidad de Santiago de Compostela, E-15705, Santiago de Compostela, Spain

    M. Castro-Gago, E. Rodrigo-Saez & I. Novo-Rodriguez

  2. Departamento de Bioquímica, Servicio de Laboratoria Central, Hospital Clinico Universitario, Universidad de Santiago de Compostela, E-15705, Santiago de Compostela, Spain

    M. F. Camiña & S. Rodriguez-Segade

Authors
  1. M. Castro-Gago
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Rodrigo-Saez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Novo-Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. F. Camiña
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Rodriguez-Segade
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Castro-Gago, M., Rodrigo-Saez, E., Novo-Rodriguez, I. et al. Hyperaminoacidemia in epileptic children treated with valproic acid. Child's Nerv Syst 6, 434–436 (1990). https://doi.org/10.1007/BF00302087

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00302087

Key words

Search

Navigation