ZAP70-Related Combined ImmunodeficiencyD81.8

Last updated on: 19.08.2021

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DefinitionThis section has been translated automatically.

ZAP70-Related Combined Immunodeficiency ( ZAP=Zeta-associated protein 70) is a very rare autosomal recessive cell-mediated immunodeficiency caused by abnormal T-cell receptor (TCR) signaling. Affected children usually suffer from recurrent bacterial, viral, and opportunistic infections, diarrhea, and failure to thrive during the first year of life. Severe lower respiratory tract infections and oral candidiasis are common. Affected children usually do not survive more than two years without hematopoietic stem cell transplantation (HSCT).

DiagnosticsThis section has been translated automatically.

The diagnosis of ZAP70-related CID is made by low to absent CD8+ T cells in a person with normal CD3+ and CD4+ T cell counts. Furthermore: lack of proliferation of CD4+ T cells in response to mitogens and antigens and lack of expression of ZAP-70 protein. Diagnosis is made in one subject by identifying biallelic pathogenic variants of ZAP70 in a molecular genetic assay.

LaboratoryThis section has been translated automatically.

Combined immunodeficiency (CID) characterized by the selective absence of circulating CD8 T cells in the presence of low, normal or elevated CD4 T cells in peripheral blood.

TherapyThis section has been translated automatically.

Treatment of manifestations: Supportive care includes immediate administration of intravenous immunoglobulin (IVIG) and antibacterial, antifungal and antiviral prophylaxis, as well as Pneumocystis jiroveci prophylaxis to control and reduce infections.

Prevention of primary manifestations: Allogeneic HSCT to restore the immune system, preferably before the onset of infections.

General therapyThis section has been translated automatically.

ZAP70-related CID is inherited in an autosomal recessive manner. At conception, each sibling of an affected person has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. If the pathogenic variants are known in the family, carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible.

ProphylaxisThis section has been translated automatically.

Prevention of secondary complications: use of irradiated, leukoreduced, cytomegalovirus (CMV)-safe blood products; vaccination with live viral, mycobacterial, and bacterial vaccines; contaminated water sources; contact with fungus-laden environments (e.g., construction sites, agricultural fields with active soil scarification, mulch, hay). Consider formula feeding in lieu of breastfeeding until the mother's CMV status is known.

Note(s)This section has been translated automatically.

To date, 14 unique mutations in the ZAP70 gene have been identified in patients with ZAP-70-related CID.

ZAP-70 deficiency should be considered in infants and young children with recurrent bacterial infections, even if the lymph nodes are palpable, the thymic shadow is conspicuous, and the total lymphocyte count is normal.

LiteratureThis section has been translated automatically.

  1. Adjali O et al (2005) In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transfer. J Clin Invest 115:2287-95.
  2. Akar HH et al (2017) Silent brain infarcts in two patients with zeta chain-associated protein 70 kDa (ZAP70) deficiency. Clin Immunol 158: 88-91.
  3. Aluri J et al. (2017) Low T cell receptor excision circles (TRECs) in a case of ZAP 70 deficient severe combined immunodeficiency (SCID) with a novel mutation from India. Blood Cells Mol Dis 65:95-96.
  4. Elder ME (1997) SCID due to ZAP-70 deficiency. J Pediatr Hematol Oncol 19:546-550.
  5. Gavino C et al (2017) Morpholino-based correction of hypomorphic ZAP70 mutation in an adult with combined immunodeficiency. J Allergy Clin Immunol 139:1688-1692.e10.
  6. Schroeder ML et al. (2016) Genotyping an immunodeficiency causing c.1624-11G>A ZAP70 mutation in Canadian Mennonites. BMC Med Genet. 17:50.

Last updated on: 19.08.2021