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Genetics Home Reference: your guide to understanding genetic conditions
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ZAP70-related severe combined immunodeficiency

Reviewed November 2009

What is ZAP70-related severe combined immunodeficiency?

ZAP70-related severe combined immunodeficiency (SCID) is an inherited disorder that damages the immune system. ZAP70-related SCID is one of several forms of severe combined immunodeficiency, a group of disorders with several genetic causes. Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people. Infants with SCID typically experience pneumonia, chronic diarrhea, and widespread skin rashes. They also grow much more slowly than healthy children. If not treated in a way that restores immune function, children with SCID usually live only a year or two.

Most individuals with ZAP70-related SCID are diagnosed in the first 6 months of life. At least one individual first showed signs of the condition later in childhood and had less severe symptoms, primarily recurrent respiratory and skin infections.

How common is ZAP70-related severe combined immunodeficiency?

ZAP70-related SCID is a rare disorder. Only about 15 affected individuals have been identified. The prevalence of SCID from all genetic causes combined is approximately 1 in 50,000.

What genes are related to ZAP70-related severe combined immunodeficiency?

As the name indicates, this condition is caused by mutations in the ZAP70 gene. The ZAP70 gene provides instructions for making a protein called zeta-chain-associated protein kinase. This protein is part of a signaling pathway that directs the development of and turns on (activates) immune system cells called T cells. T cells identify foreign substances and defend the body against infection.

The ZAP70 gene is important for the development and function of several types of T cells. These include cytotoxic T cells (CD8+ T cells), whose functions include destroying cells infected by viruses. The ZAP70 gene is also involved in the activation of helper T cells (CD4+ T cells). These cells direct and assist the functions of the immune system by influencing the activities of other immune system cells.

Mutations in the ZAP70 gene prevent the production of zeta-chain-associated protein kinase or result in a protein that is unstable and cannot perform its function. A loss of functional zeta-chain-associated protein kinase leads to the absence of CD8+ T cells and an excess of inactive CD4+ T cells. The resulting shortage of active T cells causes people with ZAP70-related SCID to be more susceptible to infection.

Related Gene(s)

Changes in this gene are associated with ZAP70-related severe combined immunodeficiency.

  • ZAP70

How do people inherit ZAP70-related severe combined immunodeficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of ZAP70-related severe combined immunodeficiency?

These resources address the diagnosis or management of ZAP70-related severe combined immunodeficiency and may include treatment providers.

  • Baby's First Test: Severe Combined Immunodeficiency (http://www.babysfirsttest.org/newborn-screening/conditions/severe-combined-immunodeficiency-scid)
  • Gene Review: ZAP70-Related Severe Combined Immunodeficiency (http://www.ncbi.nlm.nih.gov/books/NBK20221)
  • Genetic Testing Registry: Severe combined immunodeficiency, atypical (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1849236)

You might also find information on the diagnosis or management of ZAP70-related severe combined immunodeficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/zap70-related-severe-combined-immunodeficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/zap70-related-severe-combined-immunodeficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about ZAP70-related severe combined immunodeficiency?

You may find the following resources about ZAP70-related severe combined immunodeficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for ZAP70-related severe combined immunodeficiency?

  • selective T-cell defect
  • ZAP70-related SCID
  • zeta-associated protein 70 deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about ZAP70-related severe combined immunodeficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding ZAP70-related severe combined immunodeficiency?

autosomal ; autosomal recessive ; bacteria ; cell ; chronic ; deficiency ; gene ; immune system ; immunodeficiency ; infection ; inherited ; kinase ; newborn screening ; pneumonia ; prevalence ; protein ; recessive ; respiratory ; screening

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Elder ME. SCID due to ZAP-70 deficiency. J Pediatr Hematol Oncol. 1997 Nov-Dec;19(6):546-50. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9407944?dopt=Abstract)
  • Elder ME. T-cell immunodeficiencies. Pediatr Clin North Am. 2000 Dec;47(6):1253-74. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11130995?dopt=Abstract)
  • Gene Review: ZAP70-Related Severe Combined Immunodeficiency (http://www.ncbi.nlm.nih.gov/books/NBK20221)
  • Grunebaum E, Sharfe N, Roifman CM. Human T cell immunodeficiency: when signal transduction goes wrong. Immunol Res. 2006;35(1-2):117-26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17003514?dopt=Abstract)
  • Picard C, Dogniaux S, Chemin K, Maciorowski Z, Lim A, Mazerolles F, Rieux-Laucat F, Stolzenberg MC, Debre M, Magny JP, Le Deist F, Fischer A, Hivroz C. Hypomorphic mutation of ZAP70 in human results in a late onset immunodeficiency and no autoimmunity. Eur J Immunol. 2009 Jul;39(7):1966-76. doi: 10.1002/eji.200939385. (http://www.ncbi.nlm.nih.gov/pubmed/19548248?dopt=Abstract)
  • Turul T, Tezcan I, Artac H, de Bruin-Versteeg S, Barendregt BH, Reisli I, Sanal O, van Dongen JJ, van der Burg M. Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency. Eur J Pediatr. 2009 Jan;168(1):87-93. doi: 10.1007/s00431-008-0718-x. Epub 2008 May 29. (http://www.ncbi.nlm.nih.gov/pubmed/18509675?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2009
Published: December 22, 2014