Hyperhomocystinemia in children with inflammatory bowel disease

Objectives: Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Plasma total homocysteine (tHcy) is a risk factor for vascular disease and has been implicated as a mediator of thromboembolic events in adults with IBD. The authors studied the link between tHcy and IBD in children, in whom associations may be clearer, and investigated associations with plasma von Willebrand factor antigen, a marker of vascular damage. Methods: This cross-sectional study included 43 patients with IBD (27 Crohn disease, 9 ulcerative colitis, and 7 indeterminate colitis) and 46 control subjects from a pediatric gastroenterology clinic. Plasma tHcy, plasma 5-methyl tetrahydrofolate, red cell folate, plasma vitamin B-12, plasma von Willebrand factor antigen, and methylene tetrahydrofolate reductase (MTHFR) genotype (for the C677T mutation) were measured. Results: Plasma tHcy concentrations were higher in children with IBD than in control subjects, when corrected for age (P < 0.05), and plasma tHcy was negatively correlated with plasma 5 methyl tetrahydrofolate (P < 0.0005). Plasma 5 methyl tetrahydrofolate and age were the main predictors of plasma tHcy. Neither MTHFR genotype nor von Willebrand factor showed any association with any other measure, and there were no differences between children with IBD and control subjects. Conclusions: Elevated plasma tHcy is a consequence of IBD in children, probably mediated by poor folate status associated with diet or the pathophysiology of the disease.