Chronic Inflammatory Bowel Disease as Key Manifestation of Atypical ARTEMIS Deficiency

We describe a girl presenting at age 6 years with a history of chronic ulcerating intestinal inflammation since 9 months of age. She exhibited a severe, steroid-dependent clinical course of intestinal inflammation over several years in the absence of serious infections. Immunodeficiency was first considered at 6 years of age due to chronic lymphopenia. Immunophenotyping revealed low B and T cell counts with few na < ve T cells, a skewed TCR repertoire, and TCR gamma/delta T cell predominance, suggesting a defect of lymphocyte development. Genetic and functional analyses identified a hypomorphic mutation in the DCLRE1C (ARTEMIS) gene compromising V(D)J recombination efficiency, but allowing residual T and B cell development. Hematopoetic stem cell transplantation reconstituted the lymphocyte compartment and cured the inflammatory bowel disease. This report illustrates that a genetic disorder of lymphocyte development can present with chronic inflammatory bowel disease as the dominant phenotype in the absence of severe infection susceptibility.