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Hyperamino-acidaemia and hyperammonaemia in epileptic children treated with valproic acid

  • Neuropediatrics
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Abstract

Serum amino acid pattern, blood ammonia, and serum valproic acid (VPA) levels were estimated in 75 epileptic children with and without VPA therapy. The incidence of patients with hyperammonaemia (>60 μmol/l) in patients treated with only VPA or with a combination of VPA and other antiepileptic drugs was 19% and 20% respectively. Hyperammonaemia was not observed in patients receiving other drugs. Elevated levels of serum glycine, alanine and serine were more common in epileptic patients treated with VPA alone and with VPA in combination with other drugs than in patients receiving other drugs. A significant positive correlation was found between the serum levels of glycine and alanine, of glycine and serine, and of serine and alanine. These findings may indicate a mitochondrial dysfunction caused by VPA.

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Abbreviations

VPA:

valproic acid

References

  1. Addison GM, Gordon NS (1980) Sodium valproate and acute hepatic failure. Dev Med Child Neurol 22:248–249

    Google Scholar 

  2. Bartlet K (1977) Sodium valproate and hyperglycinaemia. Lancet II:716

    Google Scholar 

  3. Benavides J, Martin A, Ugarte M, Valdivieso F (1982) Inhibition by valproic acid of pyruvate uptake by brain mitochondria. Biochem Pharmacol 31:1633–1636

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  7. Donat JF, Bocchini JA Jr, Gonzalez E, Schwendimann RN (1979) Valproic acid and fatal hepatitis. Neurology 29:273–274

    Google Scholar 

  8. Dreifuss FE, Santilli N, Langer DH, Sweeny KP, Moline KA, Menander KB (1987) Valproic acid hepatic fatalities: a retrospective review. Neurology 37:379–385

    Google Scholar 

  9. Gastaut H, Noel P (1981) A case of fatal toxic hepatitis: recommendations for the administration of sodium valproate. Epilepsia 22:711–713

    Google Scholar 

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

    Google Scholar 

  11. Haas R, Chir B, Stumph DA, Parks JK, Eguren L (1981) Inhibitory effects of sodium valproate on oxidative phosphorylation. Neurology 31:1473–1476

    Google Scholar 

  12. Hayasaka K, Kochi H, Hiraga K, Kikuchi G (1980) Occurrence of a catalytically less active glycine decarboxylase in the liver of rat treated with dipropylacetic acid. Biochem Int 1:410–416

    Google Scholar 

  13. Hayasaka K, Takahashi I, Kobayashi Y, Iinuma K, Narisawa K, Tada K (1986) Effects of valproate on biogenesis and function of liver mitochondria. Neurology 36:351–356

    Google Scholar 

  14. Herranz JL, Arteaga R, Armijo JA (1982) Side effects of sodium valproate in monotherapy controlled by plasma levels: a study in 88 pediatric patients. Epilepsia 23:203–214

    Google Scholar 

  15. 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 

  16. Jacobi G, Thorbeck R, Rits A, Janssen W, Schmidts H (1980) Fatal hepatotoxicity in child on phenobarbitone and sodium valproate. Lancet I:712–713

    Google Scholar 

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

    Google Scholar 

  18. Kochi H, Hayasaka K, Hiraga K, Kikuchi G (1979) Reduction of the level of the glycine cleavage system in the rat liver resulting from administration of dipropylacetic acid: an experimental approach to hyperglycinemia. Arch Biochem Biophys 198:589–597

    Google Scholar 

  19. LeBihan G, Bourreille J, Sompson M, Leroy J, Szekely AM, Coquerel A (1980) Fatal hepatic failure and sodium valproate. Lancet II:1298–1299

    Google Scholar 

  20. Lenoir GR, Perignon J-L, Gubler M-C, Broyer M (1981) Valproic acid: a possible cause of proximal tubular renal syndrome. J Pediatr 98:502–504

    Google Scholar 

  21. Okuda H, Fujii S (1966) A direct electrophotometoric method of blood ammonia analysis (in Japanese). Saishin Igaku 21:622–627

    Google Scholar 

  22. Scheffner D (1986) Fatal liver failure in children on valproate. Lancet II:511

    Google Scholar 

  23. 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 

  24. Ware S, Millward-Sadler GH (1980) Acute liver disease associated with sodium valproate. Lancet II:1110–1113

    Google Scholar 

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

    Google Scholar 

  26. Zimmerman HJ, Ishak KG (1982) Valproate-induced hepatic injury: analyses of 23 fatal cases. Hepatology 2:591–597

    Google Scholar 

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Iinuma, K., Hayasaka, K., Narisawa, K. et al. Hyperamino-acidaemia and hyperammonaemia in epileptic children treated with valproic acid. Eur J Pediatr 148, 267–269 (1988). https://doi.org/10.1007/BF00441418

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  • DOI: https://doi.org/10.1007/BF00441418

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