XSCID

X-linked severe combined immunodeficiency (XSCID) is a primary immunodeficiency caused by mutations in the IL2RG gene located on the X chromosome. IL2RG encodes the common gamma chain, a shared subunit of receptors for several interleukins (including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21) that are essential for the development and function of T and natural killer (NK) cells. In XSCID, T cells and NK cells are markedly reduced or absent, while B cells are present but unable to mount effective antibody responses due to the lack of T cell help. The typical immunologic pattern is T- B+ NK-.

Clinically, XSCID presents in infancy with severe, recurrent infections and failure to thrive. Affected children are highly susceptible to bacterial, viral, and fungal pathogens, and may experience chronic diarrhea, pneumonia, and other opportunistic infections. Because the disease is X-linked, it primarily affects male infants, with familial carriers described in families.

Diagnosis relies on a combination of immunologic testing and genetic analysis. Lymphocyte subset analysis shows very low or absent T cells and NK cells with relative preservation of B cells, along with pan-immunoglobulin deficiencies or reduced levels. Confirmatory testing identifies pathogenic IL2RG mutations. Newborn screening using T-cell receptor excision circles (TRECs) can facilitate early detection.

Management focuses on infection prevention and definitive therapy. Prophylactic antibiotics, antifungals, and intravenous immunoglobulin (IVIG) are often used, alongside strict infection control measures. The treatment of choice is hematopoietic stem cell transplantation (HSCT) from a matched donor, ideally performed early in life. Gene therapy approaches targeting IL2RG have been explored, with ongoing research. Prognosis improves with early diagnosis and transplantation; without treatment, XSCID is usually fatal in early infancy.