(See also Overview of Immunodeficiency Disorders Overview of Immunodeficiency Disorders Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more and Approach to the Patient With an Immunodeficiency Disorder Approach to the Patient With Suspected Immunodeficiency Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more .)
ZAP-70 deficiency is a primary immunodeficiency disorder Primary Immunodeficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more that involves cellular immunity deficiencies Cellular immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more . 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 Severe Combined Immunodeficiency (SCID) Severe combined immunodeficiency is characterized by low to absent T cells and a low, high, or normal number of B cells and natural killer cells. Most infants develop opportunistic infections... read more (SCID); however, they live longer, and the deficiency may not be diagnosed until they are several years old.
Diagnosis of ZAP-70 Deficiency
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 of ZAP-70 Deficiency
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 Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers (leukemias, lymphomas, myeloma) and other hematologic disorders... read more , which is potentially curative.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
adenosine |
ADENOCARD |
