ZAP70 deficiency, or ZAP70 deficient SCID, is a rare

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosom ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

form of

severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diffe ...

(SCID) resulting in a lack of

CD8 CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-antigen int ...

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s. People with this disease lack the capability to fight infections, and it is fatal if untreated. It is cause by a mutation in the

ZAP70 ZAP-70 (Zeta-chain-associated protein kinase 70) is a protein normally expressed near the surface membrane of lymphocytes (T cells, natural killer cells, and a subset of B cells). It is most prominently known to be recruited upon antigen binding to ...

gene.

Presentation

Children with this condition typically present with infections and skin rashes. Unlike many forms of SCID, absolute lymphocyte count is normal and thymus is present.

Cause

ZAP70 deficiency SCID is caused by a mutation is the

gene, which is involved in the development of T cells.

Diagnosis

It is characterized by a lack of

s and the presence of circulating CD4+ T cells which are unresponsive to

T-cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...

(TCR)-mediated stimuli. Diagnosis is usually made within the first six months of life. Genetic testing is required.

Treatment

Hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...

is the only known cure for ZAP70 deficient SCID.

Epidemiology

ZAP70 deficiency SCID is estimated to occur in approximately 1 in 50,000 people. Fewer than fifty people with this condition have been identified.

References

External links

{{Deficiencies of intracellular signaling peptides and proteins Autosomal recessive disorders Rare diseases Combined T and B–cell immunodeficiencies