GENETIC TESTING IDENTIFIES CAUSE OF ENTEROPATHY AND GROWTH FAILURE IN A 10 YEAR OLD MALE

Abstract

Introduction Enteropathies with features of celiac disease or inflammatory bowel disease (IBD) should spark consideration of an immunodeficiency when presenting at an early age. Case Description We present a 10-year old male with chronic diarrhea starting at 6 weeks of life, initially improved with TPN, steroids, and cow's milk free diet. By 2 years of age, diarrhea returned, and he required frequent courses of steroids to manage his symptoms. The patient had mild dermatitis and poor growth, with otherwise negative review of systems. Endoscopies found duodenitis with severe villous blunting and pancolitis. Laboratory evaluations were notable for negative anti-enterocyte antibodies, elevated antigliadin and tissue transglutaminase IgA levels, and normal T regulatory (Treg) cells and forkhead box P3 (FOXP3) expression. He was diagnosed with Celiac Disease and years later, Crohn's Disease. His clinical course did not improve with gluten avoidance or various immunomodulators. Eventually, sequencing of the FOXP3 gene was performed, revealing a missense mutation consistent with Immune dysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) syndrome. Discussion IPEX is a rare syndrome caused by a mutation in the FOXP3 transcription factor of CD4+ Treg cells. The classic IPEX syndrome includes protracted diarrhea, dermatitis, and endocrinopathies, but phenotypes vary. Endoscopic findings of the IPEX enteropathy can mimic those seen in Celiac Disease and IBD, thus a high index of suspicion should be maintained in select patients with early onset of symptoms. Finally, this case highlights the importance of genetic analysis of the FOXP3 gene itself, as IPEX patients can have normal FOXP3 protein expression and Treg numbers.