Search CDDW Abstracts 2012
Return to Table of Contents
A PRESENTATION OF INFANTILE-ONSET COLITIS AND THE IDENTIFICATION OF A NEW IL10R POLYMORPHISM
P Valentino1, C Guo2, S Benseler3, C Roifman4, A Griffiths1, A Muise11Division of Gastroenterology, The Hospital for Sick Children; 2Program in Cell Biology, University of Toronto; 3Division of Rheumatology; 4Division of Immunology and Allergy, The Hospital for Sick Children, Toronto, ON
Aims: Infantile colitis is a distinct entity, different from later-onset inflammatory bowel disease (IBD). These children may have specific mutations in genes involved in the regulation of the immune system leading to disregulation and autoimmunity.
Methods: We present the case of a Caucasian female child who developed symptoms of colitis at six months of age, which was caused by a single gene mutation.
Results: The child first presented due to fever in the first week of life. She was hospitalized four times by age two months due to recurrent febrile illnesses requiring antibiotics including: rotavirus infection, peri-orbital cellulitis, and aseptic meningitis. At three months of age she developed a scalp cellulitis with pustules, generalized erythroderma and eczema. An immunodeficiency was suspected at this point, however subsequent investigations, including a thymic biopsy, were non-contributory. At approximately age five months, she developed unremitting bloody diarrhea as well as peri-anal disease with skin tags that progressed to rectovaginal fistulae requiring a diverting loop-ileostomy at age 23 months. Endoscopy was significant for the identification of colonic ulcerations with friability and both acute and chronic colitis on histology without granulomata. Her symptoms improved slightly with intravenous steroids, but there was poor response to sulfasalazine, azathioprine, anakinra, intravenous immunoglobulins or antibiotics. Subsequently, she developed large joint polyarthritis that impaired ambulation and required steroid injections. Genetic investigations identified a novel mutation at the 5' splice site of the IL10 receptor alpha chain. This impaired normal RNA splicing leading to a frame-shift, incorporation of an early stop codon at P206X and a truncated protein product. Both parents were heterozygous carriers of this mutation and were consanguineous from the same geographically isolated region of Canada.
Conclusions: IL10 polymorphisms were identified via GWAS analysis to be associated with IBD. The literature reports two children with homozygous mutations of the IL10 gene and 6 children with homozygous mutations of the IL10 receptor, with impaired signaling through STAT3. All children developed colitis before age 12 months. Here we describe a novel mutation of the IL10 receptor that was associated with infantile-onset colitis, arthritis, pustular rashes, and recurrent infections. We suspect there are other mutations causing infantile-onset colitis that have yet to be elucidated, the identification of which will have major impact on disease management.