Early-Onset Inflammatory Bowel Disease: Diagnostic and Therapeutic Challenges in a Child

Introduction Growing evidence suggests a link between specific mutations involved in monogenic autoinflammatory diseases, primary immunodeficiencies (PIDs), and early-onset inflammatory bowel disease (EIBD), including Crohn’s disease-like phenotypes. Understanding these genetic interactions is crucial for elucidating the underlying pathophysiological mechanisms and optimizing the therapeutic management of these early and complex forms of EIBD. Methods Through this case report, we aim to describe the clinical presentation and outcomes of EIBD in a 16-year-old child and to discuss etiological and therapeutic options. Results At the age of 12, the patient presented with severe hemophagocytic lymphohistiocytosis (HLH) syndrome associated with EBV infection, involving both cardiac and hepatic systems. He had a history of recurrent diarrhea since 40 days of life, hypoxemic pneumonia, and recurrent ear, nose, and throat infections. Later, he was diagnosed with Crohn-like inflammatory manifestations, including rectosigmoiditis, severe congestive colitis, and an inflammatory digestive syndrome (calprotectin >1,000 µg/g), which were resistant to immunosuppressive therapy. The immune workup revealed a decrease in NK cells and an inversion of the CD4/CD8 (T4/T8) ratio. Genetic testing identified a hemizygous mutation in the XIAP gene and a heterozygous mutation in the NLRP12 gene. The patient was considered for hematopoietic stem cell transplantation (HSCT) from his 20-year-old asymptomatic brother, a matched sibling donor (MSD). However, genetic analysis of the donor revealed the same NLRP12 mutation. While bone marrow transplantation is a potentially curative option for the XIAP mutation, its efficacy is uncertain in this case due to the coexisting NLRP12 mutation in the donor. The contribution of each mutation to the patient’s complex inflammatory manifestations remains difficult to determine. Conclusion A better understanding of the underlying immunological interactions may help identify new therapeutic targets and improve the clinical management of patients with EIBD.