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X-linked severe combined immunodeficiency (SCID)

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

INTRODUCTION

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".)

EPIDEMIOLOGY

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].

PATHOGENESIS

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 2016. | This topic last updated: Fri Oct 23 00:00:00 GMT+00:00 2015.
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References
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  1. Kwan A, Abraham RS, Currier R, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA 2014; 312:729.
  2. Al-Muhsen S, Alsum Z. Primary immunodeficiency diseases in the Middle East. Ann N Y Acad Sci 2012; 1250:56.
  3. Noguchi M, Yi H, Rosenblatt HM, et al. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 1993; 73:147.
  4. Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol 2009; 9:480.
  5. Adriani M, Garbi C, Amodio G, et al. Functional interaction of common gamma-chain and growth hormone receptor signaling apparatus. J Immunol 2006; 177:6889.
  6. De Ravin SS, Shum E, Zarember KA, et al. Short stature in partially corrected X-linked severe combined immunodeficiency--suboptimal response to growth hormone. J Pediatr Endocrinol Metab 2008; 21:1057.
  7. Wada T, Yasui M, Toma T, et al. Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome. Blood 2008; 112:1872.
  8. Shibata F, Toma T, Wada T, et al. Skin infiltration of CD56(bright) CD16(-) natural killer cells in a case of X-SCID with Omenn syndrome-like manifestations. Eur J Haematol 2007; 79:81.
  9. Slatter MA, Angus B, Windebank K, et al. Polymorphous lymphoproliferative disorder with Hodgkin-like features in common γ-chain-deficient severe combined immunodeficiency. J Allergy Clin Immunol 2011; 127:533.
  10. Speckmann C, Pannicke U, Wiech E, et al. Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency. Blood 2008; 112:4090.
  11. Wada T, Candotti F. Somatic mosaicism in primary immune deficiencies. Curr Opin Allergy Clin Immunol 2008; 8:510.
  12. Walshe D, Gaspar HB, Thrasher AJ, et al. Signal transducer and activator of transcription 5 tyrosine phosphorylation for the diagnosis and monitoring of patients with severe combined immunodeficiency. J Allergy Clin Immunol 2009; 123:505.
  13. Somech R, Roifman CM. Mutation analysis should be performed to rule out gammac deficiency in children with functional severe combined immune deficiency despite apparently normal immunologic tests. J Pediatr 2005; 147:555.