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ZAP-70 Deficiency

By

James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Last full review/revision Dec 2019| Content last modified Dec 2019
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NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version

ZAP-70 (zeta-associated protein 70) deficiency is an immunodeficiency involving impaired T-cell activation caused by a signaling defect.

ZAP-70 deficiency is a primary immunodeficiency disorder that involves cellular immunity deficiencies. Inheritance is autosomal recessive.

ZAP-70 is important in T-cell signaling and in T-cell selection in the thymus. ZAP-70 deficiency causes T-cell activation defects.

Patients who have ZAP-70 deficiency present during infancy or early childhood with recurrent infections similar to those in severe combined immunodeficiency (SCID); however, they live longer, and the deficiency may not be diagnosed until they are several years old.

Diagnosis

  • Routine neonatal screening using the T-cell receptor excision circle (TREC) test

  • White blood cell (WBC) count

  • Mitogen and vaccine antigen stimulation assays

Diagnosis of ZAP-70 deficiency is similar to that for SCID.

ZAP-70 deficiency may be suspected in older children with a history of recurrent infections or other characteristic manifestations. Complete blood count, including absolute WBC count and differential, is done; immunoglobulin levels are measured. Responses to mitogens and to standard vaccine antigens are determined to evaluate WBC and antibody function.

The disorder is considered in patients with the following:

  • Lymphopenia

  • A low number of or no T cells

  • Absent lymphocyte proliferative responses to mitogens

Other tests may be done; they include flow cytometry to determine T, B, and natural killer cell counts. Adenosine deaminase (ADA) and purine nucleoside phosphorylase levels in WBCs, red blood cells, and fibroblasts are measured.

Patients have normal, low, or elevated serum immunoglobulin levels and normal or elevated numbers of circulating CD4 T cells but essentially no CD8 T cells. Their CD4 T cells do not respond to mitogens or allogeneic cells in vitro and do not produce cytotoxic T cells. In contrast, natural killer cell activity is normal.

Treatment

  • Hematopoietic stem cell transplantation

Treatment of ZAP-70 deficiency generally involves preventing infection, managing acute infection, and replacing missing immune globulins.

The ZAP-70 deficiency is fatal unless treated by hematopoietic stem cell transplantation.

Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
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