Role of folic acid depletion on homocysteine serum level in children and adolescents with epilepsy and different MTHFR C677T genotypes

Abstract

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. An elevated total plasma Hcy concentration (tHcy) is a risk factor for vascular disease. The present study aimed to assess the role of antiepileptic drugs (AEDs) and C677T methylenetetrahydrofolate (MTHFR) polymorphisms on tHcy in pediatric patients with epilepsy treated for at least 6 months with various treatment regimens protocols including the newer AEDs. The study group was recruited from children and adolescents with epilepsy followed up in the Child Neuropsychiatry Clinic of the Second University of Naples, between January 2007 and March 2008. Inclusion criteria were: (1) patients with epilepsy, treated with one or more anticonvulsant drugs for at least 6 months; (2) age between 2 and 16 years. Plasma tHcy concentrations were considered elevated when they exceeded 10.4 μmol/L, and folate concentrations <3 ng/mL were considered deficient. Serum vitamin B12 levels were considered normal between 230 and 1,200 pg/mL. The study group was composed of 78 patients (35 males, 43 females), aged between 3 and 15 years (mean 8.9 years). Thirty-five patients were taking AED monotherapy, 43 polytherapy. Sixty-three healthy sex- and age-matched children and adolescents served as controls. The mean tHcy value in the patient group was higher than the mean value in the control group (12.11 ± 7.68 μmol/L vs 7.4±4.01 μmol/L; p<0.01). DNA analysis for the MTHFR C677T polymorphism showed the CT genotype in 46%, CC in 35% and TT in 17.8% of cases. Decreased folic acid serum levels significantly correlated with increased tHcy levels (p<0.003). Female sex was a less significant risk factor for increased tHcy levels (p=0.039). Our study confirms the association between hyperhomocysteinemia and epilepsy. The elevation of tHcy is essentially related to low folate levels. Correction of poor folate status, through supplementation, remains the most effective approach to normalize tHcy levels in patients on AED mono- or polytherapy.

Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study

“…Hence, in our study, the cut-off for defining hyperhomocysteinaemia was taken as >10.4 μmol/L, as previously suggested by Coppola et al and Huemer et al 3 11. Because of the lower cut-offs used to define hyperhomocysteinaemia in our study, 34% of control children also had raised Hcy concentrations.…”

“…An inverse relationship exists between the amount of Hcy present in the patient sample and the amount of relative light units (RLUs) detected by the system. A total Hcy value of ≥10.4 µmol/L was considered as hyperhomocysteinaemia in the children 3 11 19 20…”

Folic acid supplementation on homocysteine levels in children taking antiepileptic drugs: A randomized controlled trial

“…[820] The tHcy level exceeded the 90 th age percentile in 13.8% Japanese and 40.4% of Spanish children taking AEDs. [2122] A prospective study reported that 5 μmol/l higher tHcy level was associated with a 27% higher risk for venous thrombosis.…”

“…[8914] Considering the biological plausibility, many doctors are now prescribing folic acid to those undergoing treatment with AEDs, though there is a paucity of data from India. In this context, the present study was conducted with the following objectives: (1) to assess the level of tHcy in children taking AEDs and (2) to study whether daily oral supplementation of folic acid will reduce the tHcy level in them.…”

Functional variant in methionine synthase reductase decreases the risk of Down syndrome in China

“…t‐Hcy levels were determined via fluorescence polarization immunoassay. The serum folate concentration was determined using commercial kits (ACS180 PLUS: Ciba‐Corning, Tianjin, China; and Immulite: Diagnostic Products Corporation, Tianjin, China) as described in detail by Coppola et al 21 …”