Gene Mutations Linked to IBD in Children

Study Shows Mutations May Spur Severe Early-Onset Inflammatory Bowel Disease

Medically Reviewed by Louise Chang, MD on November 18, 2009
From the WebMD Archives

Nov. 19, 2009 -- Rare genetic mutations may trigger inflammatory bowel disease (IBD) in young children.

A new study shows genetic mutations affecting the interleukin-10 receptor are associated with severe early-onset IBD in children; a stem cell transplant was successful in putting the disease into remission in one child affected by the disease.

"Our study provides an example of the power of molecular medicine to go from the bedside (for diagnosis) to the bench (for the discovery of mutations) and back to the bedside (for treatment)," write researcher Erik-Oliver Glocker, MD, of the Royal Free Hospital and University College London, and colleagues in the New England Journal of Medicine.

Inflammatory bowel disease affects about 2 million children and adults in the U.S. The disease results in inflammation of the gastrointestinal lining, causing damage and ulcerations. IBD includes Crohn's disease, which affects any part of the gastrointestinal (GI) tract, and ulcerative colitis, which is limited to the large intestine.

In the study, researchers screened genetic samples from two unrelated families with children affected by childhood IBD and six additional children with early-onset colitis for mutations in the interleukin-10 receptor genes.

They found three distinct genetic mutations in four of nine patients with early-onset colitis. The mutations interfered with the formation of the interleukin-10 receptor. Interleukin-10 keeps excessive inflammation in check. Without adequate interleukin-10 receptors, the body can't use interleukin-10 in the way it should.

One affected child was treated with stem cell transplantation and experienced a complete remission of the disease.

Researchers say interleukin receptors are found on many cells in both the non-immune and immune system, and further studies are needed to determine which types of cells are primarily responsible for the inflammation associated with inflammatory bowel disease.

Another study released earlier this week also demonstrated a link between the interleukin gene and childhood IBD. Experts say the new findings should stimulate further research into genetic therapies for the disease.

"This study should spur new energy to fuel the search for genetic and functional contributions by interleukin-10 ... in understanding the pathogenesis of inflammatory bowel disease and to reevaluate therapeutic strategies," writes Brian Kelsall, MD, of the National Institutes of Health, in an editorial that accompanies the study.