Anti-epileptic drug treatment in children: hyperhomocysteinaemia, B-vitamins and the 677C-->T mutation of the methylenetetrahydrofolate reductase gene

Eur J Paediatr Neurol. 2000;4(6):269-77. doi: 10.1053/ejpn.2000.0379.


The aim of the study was to observe the influence of carbamazepine and valproic acid on plasma total homocysteine and B-vitamin status and the gene-drug interaction with the 677C-->T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Plasma total homocysteine concentrations were determined in 136 epileptic children taking anti-epileptic drugs as monotherapy. Nutritional (folate, B12 and B6 vitamins) and genetic (MTHFR 677 C-->T) determinants of plasma homocysteine were studied in a random sample of 59 of the 136 epileptic children. Total homocysteine concentrations were significantly increased (p < 0.05) and folate and vitamin B6 levels were significantly decreased (p < 0.01) in the children taking anti-epileptic drugs compared with our reference ranges. In the carbamazepine-treated group, significantly positive correlation was found between duration of treatment and homocysteine concentration (p < 0.01). Homocysteine concentrations showed a significantly negative correlation with vitamin levels (folate: p = 0.002, and vitamin B12: p = 0.017) only in the carbamazepine treated group. In children treated with carbamazepine up to 3 years, total homocysteine concentration correlated negatively only with folate (p = 0.003), while in patients treated for more than 3 years, total homocysteine correlated negatively only with vitamin B12 values (p = 0.007). The lowering action of carbamazepine treatment on folate levels seems to be associated with hyperhomocysteinaemia, which seems to be related to the homozygous condition for the MTHFR 677C-->T mutation. Valproic acid treatment, although also associated with hyperhomocysteinaemia, only shows a lowering effect on vitamin B6 levels, which seems to be independent of the MTHFR genotype.

MeSH terms

  • Adolescent
  • Anticonvulsants / adverse effects*
  • Carbamazepine / adverse effects
  • Child
  • Child, Preschool
  • Folic Acid / blood*
  • Genotype
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / etiology*
  • Infant
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Mutation / drug effects*
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Pyridoxine / blood*
  • Valproic Acid / adverse effects


  • Anticonvulsants
  • Homocysteine
  • Carbamazepine
  • Valproic Acid
  • Folic Acid
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Pyridoxine