ab21219

Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: A pilot study

M. Huemer, M. Födinger, C. Huemer, M. Sailer-Höck, J. Falger, A. Rettenbacher, M. Bernecker, G. Artacker, H. Kenzian, T. Lang, S. Stöckler-Ipsiroglu

Department of Pediatrics, University of Vienna, Vienna, Austria

ABSTRACT
Objective
Our first objective was to compare plasma total homocysteine (tHcy) concentrations in juvenile idiopathic arthritis (JIA) patients requiring methotrexate (MTX) treatment and healthy children. Our second aim was to evaluate the influence of low-dose (10-15 mg/m²/week) MTX treatment combined with folic acid supplementation (1 mg/d) or placebo on tHcy concentrations in JIA patients.

Methods
In 17 JIA patients and 17 age- and sex-matched healthy children, baseline tHcy concentrations were measured. When MTX treatment was initiated, JIA patients were randomly assigned to folic acid 1 mg/d/p.o. followed by placebo (8 weeks each) or vice versa. Blood samples for measurement of tHcy, vitamin B6, B12 and folate were taken after 4 weeks, 12 weeks and 20 weeks of treatment.

Results
1) In the healthy children the mean tHcy concentration was 6.3 ± 1.68 mmol/l as compared to 9.99 ± 5.17 mmol/l in JIA patients (p < 0.04). At baseline, 5/17 JIA patients had tHcy concentrations > 10.5 mmol/l, the 99th percentile for teenagers. 3/5 patients even exceeded the upper normal level for adults (tHcy ³ 15 mmol/l). MTX treatment did not result in a significant increase of tHcy and folic acid supplementation had no significant impact on tHcy levels.

Conclusion
This pilot study shows that patients with JIA requiring MTX treatment have significantly elevated baseline plasma tHcy concentrations compared to age- and sex-matched healthy controls. No significant impact of MTX and folate supplementation on tHcy concentrations was found.

Key words
Homocysteine, folic acid, methotrexate, juvenile idiopathic arthritis, genetic polymorphisms.

Supported by the 1998 grant for "Research in Pediatric Rheumatology" donated by Prof. Josef Smolen, Vienna, Austria.
Please address correspondence to: Dr. Martina Huemer, Landeskrankenhaus Feldkirch, Department of Pediatrics, Carinagasse 47, 6805 Feldkirch, Austria. E-mail: m333.huemer@aon.at