ZAP70 deficiency

A rare genetic disorder affecting the immune system

ZAP70 deficiency is a rare primary immunodeficiency disorder characterized by a defect in the ZAP-70 protein, which is crucial for T cell receptor signaling. This condition leads to severe combined immunodeficiency (SCID), affecting the body's ability to fight infections.

Pathophysiology

Autosomal recessive inheritance pattern

ZAP-70, or zeta-chain-associated protein kinase 70, is a tyrosine kinase that plays a critical role in the signaling pathways of T cells. It is essential for the activation and development of T lymphocytes, which are vital components of the adaptive immune system. In individuals with ZAP70 deficiency, mutations in the ZAP70 gene lead to a non-functional protein, impairing T cell receptor signaling. This results in the failure of T cell development and function, particularly affecting CD8+ T cells, while CD4+ T cells may be present but are non-functional.

Clinical Presentation

Patients with ZAP70 deficiency typically present in infancy with recurrent infections, failure to thrive, and chronic diarrhea. The lack of functional T cells leads to increased susceptibility to opportunistic infections, including viral, bacterial, and fungal pathogens. Common infections include pneumonia, chronic diarrhea, and oral thrush.

Diagnosis

Diagnosis of ZAP70 deficiency involves a combination of clinical evaluation, immunological testing, and genetic analysis. Laboratory findings often reveal normal or elevated levels of immunoglobulins but a marked reduction in CD8+ T cells. Genetic testing can confirm mutations in the ZAP70 gene, which are typically inherited in an autosomal recessive pattern.

Treatment

The primary treatment for ZAP70 deficiency is hematopoietic stem cell transplantation (HSCT), which can restore immune function by providing the patient with healthy donor stem cells capable of developing into functional T cells. Prior to transplantation, patients may require supportive care, including prophylactic antibiotics and immunoglobulin replacement therapy, to manage infections and other complications.

Prognosis

With successful HSCT, patients with ZAP70 deficiency can achieve normal immune function and lead healthy lives. However, without treatment, the condition is life-threatening due to the severe immunodeficiency and associated complications.

Related pages

• Severe combined immunodeficiency
• Primary immunodeficiency
• T cell receptor
• Hematopoietic stem cell transplantation