Anti-Epileptic drug treatment in children: Hyperhomocysteinaemia, B-Vitamins and the 677C→T Mutation of the Methylenetetrahydrofolate Reductase Gene

Vilaseca, M. A.; Monrós, Eugènia; Artuch, Rafael; Colomé, Catrina; Farré, Carme; Valls, Carme; Cardo, Esther; Pineda, Merçè

doi:10.1053/ejpn.2000.0379

Cited by 59 publications

(53 citation statements)

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“…None of the enrolled subjects was treated with estrogens or theophylline, two drugs known to interfere with Hcy metabolism [22, 23]. Only 1 HDF patient was receiving carbamazepine, an anti-epilectic drug able to increase plasma Hcy levels [24]. The extracorporeal dialysis treatment was carried out three times per week and each session lasted 4 h. The patients on peritoneal dialysis were dialyzed with 12–15 liters daily with an average glucose concentration of 1.36%.…”

Section: Methodsmentioning

confidence: 99%

Homocysteinemia Correlates with Plasma Thiol Redox Status in Patients with End-Stage Renal Disease

et al. 2008

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Background/Aims: In end-stage renal disease (ESRD), hyperhomocysteinemia is a common finding associated with increased cardiovascular risk. However, the pathogenic role of homocysteine is still unclear. In vitro studies show that thiol redox status affects endothelial cell functions. We therefore investigated the possible association between homocysteinemia and plasma thiol redox status in ESRD patients. Methods: Total plasma homocysteine (Hcy), cysteine (Cys) and free thiols (SH) were measured both before and after a dialytic session in 54 ESRD patients receiving (n = 15) or not receiving (n = 39) folate supplementation, and 17 control subjects. Results: High predialysis levels of both Hcy and Cys were found to be negatively correlated with low SH levels both in supplemented (r = –0.680, p < 0.01 and r = –0.624, p < 0.02, respectively) and unsupplemented (r = –0.698, p < 0.001 and r = –0.445, p < 0.01, respectively) patients. Following dialysis, SH values returned to normal and the above correlations were no longer appreciable. Conclusion: A strong, folate therapy-insensitive association between homocysteinemia and plasma free thiol levels was found in ESRD patients. These results support a role for oxidative stress in ESRD-related hyperhomocysteinemia and suggest the plasma thiol redox status alteration as a possible pathogenic mechanism underlying the cardiovascular toxicity of hyperhomocysteinemia in these patients.

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Section: Methodsmentioning

confidence: 99%

Homocysteinemia Correlates with Plasma Thiol Redox Status in Patients with End-Stage Renal Disease

et al. 2008

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“…It is known that tHcy concentrations exceeding the 95 th age percentile are related to a fourfold increased risk for ischemic cerebrovascular disease in childhood (14). Hyperhomocysteinemia has been observed in ≤40% of patients receiving antiepileptic drugs (AEDs) (15). Adults with epilepsy have a threefold increased risk for fatal cardiovascular incidents, and neural tube defects are seen more frequently in the offspring of women taking AEDs (16).…”

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confidence: 99%

Hyperhomocysteinemia in Children Treated with Antiepileptic Drugs Is Normalized by Folic Acid Supplementation

Huemer

Ausserer

Graninger³

et al. 2005

Epilepsia

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Summary:Purpose: To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients.Methods: 123 patients from three regional hospitals participated in the study. Patients with hyperhomocysteinemia were included in a 3-month double-blind randomized trial testing oral folic acid supplementation (1 mg/day) versus placebo.Results: Hyperhomocysteinemia (tHcy >10.4 µmol/L) was present in 19 of 123 patients. Patients with hyperhomocysteinemia were older (13.7 ± 4 vs. 11.0 ± 3.9 years) and had significantly lower folate and cobalamin concentrations. Multidrug (two or more) AED treatment and duration of therapy correlated significantly with elevated total homocysteine (tHcy) and low folate. In contrast, polymorphisms in the methylene tetrahydrofolate reductase gene (MTHFR 677 C→T, 1298 A→C, 1793 G→A) had no significant impact on tHcy. Nine of 19 patients with hyperhomocysteinemia were randomized to placebo, whereas the remaining 10 patients received folic acid supplementation. Folic acid supplementation resulted in a significant increase of folate and decrease of tHcy, whereas both parameters remained unchanged in the placebo group.Conclusions: Hyperhomocysteinemia is present in 15.5% of children receiving long-term AED treatment. Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia. Folic acid supplementation significantly reduces tHcy. We recommend assessment of serum folate and plasma tHcy in children receiving AEDs.

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“…The resistance in response may be due to MTHFR (C677T and A1298C) gene polymorphisms that may alter the individual response to a drug despite having patients' plasma levels in therapeutic range. As MTHFR gene polymorphisms affect DNA methylation leading to differential gene expression that can influence the drug response, hence, poor response may be attributed to low level of vitamin B 6 as well [14][15][16][17][18] . On the other hand, vitamin B 6 is responsible for synthesis of GABA which regulates the functions of alpha, beta and gamma subunits of GABA receptors 19 .…”

Section: Discussionmentioning

confidence: 99%

Vitamin B<sub>6</sub> and homocysteine levels in carbamazepine treated epilepsy of Khyber Pakhtunkhwa

et al. 2017

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Objectives: The study focused on the plasma levels of vitamin B 6 and homocysteine in different genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes in carbamazepine resistant epilepsy in the population of Khyber Pakhtunkhwa. Methodology: Patients who were possible candidates for carbamazepine therapy were followed for six months for their seizure control. Plasma levels of vitamin B 6 and homocysteine were determined using immunoassay based techniques at baseline and after six months. MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes were genotyped using restriction fragment length polymorphisms. Seizure control during therapy was recorded on a standardized proforma. Results: Low vitamin B 6 levels and hyperhomocysteinemia were found in 61.7% of resistant patients (n=34). Resistant patients had the following frequencies of variant genotypes (677CT=38.1% and 677TT=24.4%; 1298AC=42.2% and 1298CC=26.1%; 588CT= 47.6% and 315TT= 33.3%) of MTHFR (C677T and A1298C) and GABRG2 (C588T and C315T) genes. A significant decline in vitamin B 6 (P<0.0001) and hyperhomocysteinemia were found in variant genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes. Conclusion: Following six months of carbamazepine of therapy in heterozygous variant genotypes of MTHFR (677CT and 1298AC) and GABRG2 (588CT and 315CT) genes, we observed a significant fall in vitamin B 6 levels and hyperhomocysteinemia.

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Anti-Epileptic drug treatment in children: Hyperhomocysteinaemia, B-Vitamins and the 677C→T Mutation of the Methylenetetrahydrofolate Reductase Gene

Cited by 59 publications

References 0 publications

Homocysteinemia Correlates with Plasma Thiol Redox Status in Patients with End-Stage Renal Disease

Homocysteinemia Correlates with Plasma Thiol Redox Status in Patients with End-Stage Renal Disease

Hyperhomocysteinemia in Children Treated with Antiepileptic Drugs Is Normalized by Folic Acid Supplementation

Vitamin B<sub>6</sub> and homocysteine levels in carbamazepine treated epilepsy of Khyber Pakhtunkhwa

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