Clin Immunol. 2022 Jul;240:109047. doi: 10.1016/j.clim.2022.109047. Epub 2022 May 22.

Judith Kelsen ¹, Noor Dawany ², Maire Conrad ¹, Trusha Patel ¹, Marcella Devoto ³, Kelly Maurer ⁴, Kathleen E Sullivan ⁵

Author information

¹Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA.

²Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA.

³Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA.

⁴The Division of Allergy Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA.

⁵The Division of Allergy Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA. Electronic address: sullivank@chop.edu.

Abstract

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Treatment for patients who have a monogenic cause of their IBD, often the youngest children, known as very early onset IBD (VEO-IBD), can be different from standard treatment for polygenic cases. Yet, ascertainment of these patients is difficult.

Methods: We analyzed cases of VEO-IBD to understand the breadth of monogenic etiology and to identify clinical, laboratory, and flow cytometric correlates of this subpopulation.

Results: Genetic causes of very early onset inflammatory bowel disease are highly diverse ranging from pure epithelial defects to classic T cell defects. Flow cytometry, other than testing for chronic granulomatous disease, has a low sensitivity for monogenic etiologies. Poor growth was a clinical feature associated with monogenic causality.

Conclusions: Genetic testing is, at this moment, the most robust method for the identification of monogenic cases of very early onset IBD.