Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation.
OBJECTIVE
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 micromol/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.
Huemer
Martina
M
Department of Pediatrics, Academic Teaching Hospital Landeskrankenhaus (LKH), Feldkirch, Austria. martina.huemer@lkhf.at
Ausserer
Bernd
B
Graninger
Gunther
G
Hubmann
Michael
M
Huemer
Christian
C
Schlachter
Kurt
K
Tscharre
Arthur
A
Ulmer
Hanno
H
Simma
Burkhard
B
D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D019587:Dietary Supplements; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D005494:Folic Acid Deficiency / Q000097:blood / Q000188:drug therapy; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use
D000927:Anticonvulsants; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12