Evaluating IFN-γ ELISpot in a pediatric case: Unraveling X-linked leaky severe combined immunodeficiency and Omenn syndrome

Background: Mutations in the interleukin-2 receptor γ-chain gene (IL2RG) cause the X-linked T–B+ severe combined immunodeficiency (X-SCID), also termed common γ (γc) chain deficiency. Hypomorphic IL2RG variants that diminish surface expression of the γc molecule (CD132) can produce atypical clinical and immunological phenotypes. Affected patients typically display absent or markedly reduced T- and natural-killer (NK)-cell numbers while retaining normal B-cell counts. Case presentation: We describe a three-month-old boy who developed recurrent bacterial and viral infections, erythroderma, and chronic diarrhoea. The initial differential diagnosis comprised leaky SCID with Omenn syndrome and SCID with presumed transplacentally acquired maternal T-cell engraftment (TME) and graft-versus-host disease (GVHD). Comprehensive immunological work-up and targeted genetic analysis confirmed X-SCID. Conclusion: This report underscores the importance of prompt recognition and systematic evaluation of infants with recurrent infections, erythroderma, and chronic diarrhoea. Overlapping features of Omenn syndrome and maternal T-cell engraftment may obscure the diagnosis, highlighting the need for early immunological and molecular investigations. Timely identification of X-SCID is crucial to improve survival and prevent irreversible sequelae. The case supports universal newborn SCID screening and a multidisciplinary approach to the management of complex primary immunodeficiencies.