Saima Mehmood, Saba Siddiqui, Madia Kazmi, Meino Rohlfs, Christoph Klein, Huma Cheema, Daniel Kotlarz, Sonia Qureshi
We report monozygotic twin brothers presenting in early infancy with severe, recurrent diarrhoea and profound T-cell lymphopenia. Immunological evaluation showed markedly reduced immunoglobulins and very low CD3+, CD4+and CD8+ T cell subsets. Rapid progression of symptoms prompted genetic testing, which identified a novel homozygous TRAC frameshift mutation (c.315del p.Thr106GlnfsTer5) causing complete loss of protein expression. This mutation produced a more severe phenotype than previously described TRAC variants which typically retain partial gene function and present later with mixed infections or immune dysregulation. The clinical picture of the twins mimicked very-early-onset inflammatory bowel disease, highlighting the expanding phenotypic spectrum of TRAC deficiency. Early recognition of T-cell defects and timely genetic testing are essential, particularly in regions with high consanguinity and limited access to curative haematopoietic stem cell transplantation. This case underscores the urgent need for improved diagnostic capacity, international collaboration and awareness of rare primary immunodeficiency disorders.