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X-linked severe combined immunodeficiency (SCID)

Francisco A Bonilla, MD, PhD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS


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. An overview of specific 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) [1]. X-SCID is a smaller proportion of SCID in regions of the world where parental consanguinity is common [2].


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]) [3]. This receptor subunit is shared by at least six different cytokine receptor complexes: the receptors for interleukins-2, -4, -7, -9, -15, and -21 [4]. 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 [5]. 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 [6]. 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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Literature review current through: Nov 2017. | This topic last updated: Sep 26, 2017.
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