Beyond Infection: Could Infantile Colitis Signal a Rare Immunodeficiency?

Introduction Infantile colitis represents a diagnostic challenge due to its heterogeneous etiologies, including infectious, inflammatory, and immunological causes. While most cases are benign, some may reveal rare primary immunodeficiencies requiring thorough investigation and specialized management. Case Presentation We report a 17-month-old infant, born to second-degree consanguineous parents, with severe asymmetric intrauterine growth restriction. At 4 months, he was admitted for febrile abdominal distension, diarrhea, and vomiting. Surgical exploration revealed peritonitis secondary to a punctiform gastric perforation, with intraoperative cultures growing two non-groupable streptococcal species. At 8 months, the child was readmitted for chronic diarrhea, associated with grade III anitis, failure to thrive, and moderate malnutrition. Stool culture yielded extended-spectrum beta-lactamase–producing Klebsiella pneumoniae. Gastrointestinal endoscopy appeared macroscopically normal, but histopathology showed inflammatory and dystrophic changes of the duodenal and intestinal mucosa without identifiable pathogens, suggesting a noninfectious, likely immunodeficiency-related etiology. Despite transient improvement with targeted antibiotics, intravenous immunoglobulins, and enteral nutrition, relapse occurred six months later. The patient also exhibited facial dysmorphism, congenital cytomegalovirus fetopathy, recurrent severe infections (multidrug-resistant urinary tract infection, nosocomial sepsis with pulmonary abscess), persistent neutropenia, and microcytic hypochromic anemia. Immunological workup revealed combined immunodeficiency, and genetic analysis confirmed a mutation in the HELLS gene, establishing immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome type 4. The child currently receives regular intravenous immunoglobulin replacement and antimicrobial prophylaxis and is a candidate for allogeneic hematopoietic stem cell transplantation. Conclusion Chronic infantile colitis associated with severe recurrent infections and dysmorphic features should prompt evaluation for rare primary immunodeficiencies such as ICF4, as early diagnosis is crucial for management and prognosis.