Meyahealth
HomeGeneticsConditionZAP70-related severe combined immunodeficiency
Back to Condition
ZAP70-related severe combined immunodeficiency
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

ZAP70-related severe combined immunodeficiency

ZAP70-related severe combined immunodeficiency (SCID) is a rare inherited disorder that severely impairs the immune system, leaving affected children vulnerable to repeated, life-threatening infections due to a lack of immune protection.

Overview

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.

Frequency

ZAP70-related SCID is a rare disorder. Only about 20 affected individuals have been identified. The prevalence of SCID from all genetic causes combined is approximately 1 in 50,000.

Causes

As the name indicates, this condition is caused by variants (also called 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.

Variants 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.

Gene Associated with ZAP70-related Severe Combined Immunodeficiency

  • ZAP70

Inheritance

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

Other Names

  • Selective T-cell defect
  • ZAP70-related SCID
  • Zeta-associated protein 70 deficiency

Frequently Asked Questions

Even after a successful transplant, long-term follow-up is essential. Children will need ongoing monitoring of their immune function, regular vaccinations (once immune system is stable), and careful management of any potential transplant-related complications like graft-versus-host disease. They may also require lifelong immune globulin replacement or other supportive therapies, and regular check-ups with an immunologist to ensure continued health and prevent late complications.
Parents should be highly vigilant for any signs of infection, as they can quickly become life-threatening. Critical warning signs include persistent fever, difficulty breathing, a cough that worsens, chronic diarrhea, widespread or unusual skin rashes, poor feeding, or a lack of energy and responsiveness. Any of these symptoms warrant immediate medical evaluation.
The most effective treatment for ZAP70-related SCID is hematopoietic stem cell transplantation (HSCT), often referred to as a bone marrow transplant. This procedure replaces the faulty immune system with healthy stem cells. Gene therapy is also an emerging option. Without successful immune reconstitution, children typically do not survive beyond early childhood due to severe infections. Early diagnosis and treatment significantly improve outcomes.
Diagnosis often begins with newborn screening in some regions, which can identify a lack of T cells. If SCID is suspected, further tests include a complete blood count with differential to assess lymphocyte numbers, specialized flow cytometry to count specific immune cell types (T cells, B cells, NK cells), and genetic testing to confirm variants in the ZAP70 gene. Immune function tests may also be performed.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ