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About Sickkids
About SickKids

September 3, 2014

SickKids study finds genetic changes that increase susceptibility to IBD in infants and young children

A recent study led by The Hospital for Sick Children (SickKids) describes an important genetic discovery that could lead to more individualized treatment for young children with very early onset inflammatory bowel disease. The study is published in the September issue of Gastroenterology.

Very early onset IBD, also called infantile IBD, is a severe form of the disease that affects children under six years of age. The symptoms of this condition, like inflammation of the colon, often resemble that of a genetic disorder called chronic granulomatous disease (CGD) which is caused by defects to the NADPH oxidase complex and reduces the immune system cells’ ability to kill bacteria in the body. About 40 per cent of patients with CGD develop a form of IBD called Crohn’s disease.

Dr. Aleixo Muise, Co-Director of the SickKids IBD Centre and Clinician-Scientist at SickKids, and his team wanted to know if there was a link between the defective genes in CGD and the young patients they see with infantile IBD. To do this, they performed targeted exome sequencing on the genes that encode NADPH oxidase complex in 122 patients with very diagnosed at SickKids from 1994 to 2012. They found that one third of these patients had defects in the genes that encode the NADPH pathway. Further tests demonstrated that defects in these genes resulted in the immune cells’ inability to kill bacteria in the intestine.

“Understanding the root cause of IBD in an individual patient (or patient population) is critical to treating their disease. Our finding points to how we can tailor therapy to the specific genetic changes that impact the body’s ability to kill bacteria in the gut,” says Muise who is also Associate Professor in the Department of Paediatrics at the University of Toronto.

The next steps are to look more closely at the NADPH pathway to see if it is also involved in older children with IBD as well as in kids with rheumatoid arthritis.

“The big goal is to provide precise medicine to our patients, and this is a great example of a patient population where we think it is possible to go from genetic discovery to novel therapeutic relatively quickly,” adds Muise.

This research was supported by Canadian Institutes of Health Research (CIHR) and Leona M. and Harry B. Helmsley Charitable Trust to study Very Early Onset IBD.