Atypical X-Linked Severe Combined Immunodeficiency in a Patient With Early-Onset Inflammatory Bowel Disease

Primary immunodeficiency disorders may present with gastrointestinal inflammation resembling inflammatory bowel disease (IBD), particularly in patients with pediatric or very-early-onset disease. We report a 24-year-old male with lifelong immune dysregulation and early-onset IBD who was ultimately found to carry a hemizygous intronic IL2RG variant (c.270-14C>G). Despite extensive infectious complications, lymphoproliferative disease, and chronic lung pathology, his Crohn's-like intestinal inflammation had been managed successfully with azathioprine. Genome sequencing followed by RNA analysis demonstrated that the IL2RG variant introduced a cryptic splice acceptor site, causing aberrant splicing, intron retention, and a premature stop codon, confirming a diagnosis of atypical or hypomorphic X-linked severe combined immunodeficiency (X-SCID). This case expands the phenotypic spectrum of X-SCID to include chronic IBD-like enterocolitis and underscores the diagnostic utility of comprehensive genomic and transcriptomic testing in patients with complex, unexplained immune and gastrointestinal disease. Recognition of atypical presentations of X-SCID has implications for surveillance, prognosis, and consideration of definitive therapies.