Anti-epileptic drug treatment in children: hyperhomocysteinaemia, B-vitamins and the 677C-->T mutation of the methylenetetrahydrofolate reductase gene.
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.
Servei de Bioquímica, Hospital Sant Joan de Déu, Barcelona, Spain. vilaseca@hsjdbcn.org
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Vilaseca
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Monrós
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Artuch
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Colomé
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Farré
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Valls
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Cardo
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D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005492:Folic Acid / Q000097:blood*; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000209:etiology*; D007223:Infant; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation / Q000187:drug effects*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011736:Pyridoxine / Q000097:blood*; D014635:Valproic Acid / Q000009:adverse effects
D000927:Anticonvulsants; D006710:Homocysteine; D002220:Carbamazepine; D014635:Valproic Acid; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D011736:Pyridoxine