X-linked severe combined immunodeficiency (SCID)
- Francisco A Bonilla, MD, PhD
Francisco A Bonilla, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Associate Professor of Pediatrics
- Harvard Medical School
X-linked severe combined immunodeficiency (X-SCID) is due to defects in the common gamma chain (gamma-c, interleukin-2 receptor gamma [IL2RG]).
X-SCID is discussed here. Other forms of SCID and a general overview of SCID are presented separately. (See "Severe combined immunodeficiency (SCID): Specific defects" and "Severe combined immunodeficiency (SCID): An overview".)
In a cohort of 42 severe combined immunodeficiency (SCID) infants diagnosed prospectively by newborn screening in the US, nine (21 percent) had X-linked SCID (SCIDX1 or X-SCID, MIM 300400) . X-SCID is a smaller proportion of SCID in regions of the world where parental consanguinity is common .
X-linked severe combined immunodeficiency (X-SCID) is caused by defects in a gene on the X chromosome encoding the cytokine receptor subunit gamma-c (the interleukin receptor common gamma chain [IL2RG]) . This receptor subunit is shared by at least six different cytokine receptor complexes: the receptors for interleukins-2, -4, -7, -9, -15, and -21 . Mutations in this gene lead to profound derangement of the immune system via the blockade of multiple cytokine pathways important for lymphocyte development and function.
The gamma-c subunit is also involved in growth hormone receptor signaling . Thus, growth failure seen in children with X-SCID may be due to both the underlying genetic defect and to recurrent infections and nutritional deficiencies . This could explain why many patients continue to have growth failure with severe short stature after partial correction of the defect with hematopoietic cell transplantation.
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