Diagnosis of very early-onset inflammatory bowel disease

I: Initial evaluation – Patient and family history, physical examination, endoscopic investigations, imaging, and limited biochemistry and microbiology/virology tests are required to establish the diagnosis of IBD, assess disease localization and behavior, and determine inflammatory activity. If there is doubt, those tests can contribute to exclude the much more frequent GI infections and non-IBD immune responses toward dietary antigens. CMPA can present with enteropathy and colitis, and celiac disease can mimic autoimmune enteropathies. Fecal calprotectin can be helpful but may be increased even in healthy infants.
II: Functional screening, followed by genetic confirmation strategy – The diagnostic strategy to investigate a monogenic cause of IBD-like intestinal inflammation is largely based on restricted functional screening, followed by genetic confirmation. A restricted set of laboratory tests is needed to propose candidate genes of the most common genetic defects for subsequent limited sequencing.
III: Genetic screening, followed by functional confirmation strategy – As a complementary approach, genetic screening for IBD-causative rare variants using next-generation sequencing might be followed by limited functional confirmatory studies. The complexity of problems in these children requires interdisciplinary support, including pediatric gastroenterologists, immunologists, geneticists, and infectious disease specialists.