Relative CD4 lymphopenia and a skewed memory phenotype are the main immunologic abnormalities in a child with Omenn syndrome due to homozygous RAG1-C2633T hypomorphic mutation.

[omenn syndrome]

We report a child with Omenn syndrome (OS ) due to homozygous RAG 1 -C 2 633 T mutations who had an unusual clinical and immunological presentation . She had delayed onset of OS-associated clinical features , had cleared a number of potentially fatal pathogens including respiratory syncytial virus , parainfluenza-3 virus and rotavirus , and was thriving at diagnosis . Laboratory assessment showed normal T and B lymphocyte number and function . T -cell-receptor repertoire in the blood was relatively diverse and her primary immunologic abnormality was skewing of circulating T -cells to the memory phenotype . A compelling explanation for the perplexing combination in OS of atopic /autoimmune and immunologic features has proven elusive . Homozygous RAG 1 -C 2 633 T hypomorphic mutation may lead to significant residual immunity and a skewed memory phenotype . Our findings suggest that , in addition to host-genetic factors , environment , and /or pathogens , hypomorphic RAG mutations may differentially impact on V (D )J recombination activity and hence lead to a variable ability to sustain T and B cell lymphopoiesis . Importantly , this case emphasizes that such hypomorphic mutations may promote an attenuated phenotype , complicating the diagnosis of primary immunodeficiency (PID ).