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

Objective Long-term therapy with phenytoin and carbamazepine is known to cause hyperhomocysteinaemia. We evaluated the prevalence of hyperhomocysteinaemia in North Indian children receiving phenytoin or carbamazepine monotherapy for > 6 months duration and the effect of folic acid supplementation on plasma homocysteine. Methods In this cross-sectional observational study we enrolled consecutive children aged 2-12 years with epilepsy who had received phenytoin or carbamazepine monotherapy for > 6 months. Plasma total homocysteine, folic acid, vitamin B12 and antiepileptic drug concentrations were measured. Healthy age-and sex-matched controls were recruited. Children with homocysteine > 10.4 mu mol/L received folic acid supplementation for 1 month and homocysteine and folic acid concentrations were measured after 1 month follow-up. Results A total of 112 children receiving antiepileptic monotherapy for > 6 months were enrolled. Hyperhomocysteinaemia was present in 54 children (90%) receiving phenytoin, 45 children (90%) receiving carbamazepine therapy and 17 (34%) controls (p< 0.05). Mean plasma homocysteine concentrations were significantly higher (18.9 +/- 10.2 vs 9.1 +/- 3 mu mol/L) and serum folic acid concentrations (10.04 +/- 8.5 ng/ml vs 12.6 +/- 4.8 p< 0.001) and vitamin B12 concentrations (365 +/- 155 pg/mL vs 474 +/- 332 pg/mL, p = 0.02) were significantly lower in the study group compared with the control group. Duration of antiepileptic drug therapy correlated significantly with elevated homocysteine and reduced folic acid concentrations (p< 0.05). Supplementation with folic acid for 1 month led to a reduction in plasma homocysteine concentrations in the study group (from 20.9 +/- 10.3 mu mol/L to 14.2 +/- 8.2 mu mol/L, p< 0.05). Conclusions Phenytoin or carbamazepine monotherapy for >6 months duration is associated with hyperhomocysteinaemia in 90% of North Indian children. Elevated homocysteine concentrations were normalised in these children with folic acid supplementation.