Summary about Disease
ZAP70-associated Severe Combined Immunodeficiency (ZAP70-SCID) is a rare, inherited disorder of the immune system. It is a type of SCID, characterized by a profound deficiency of T cells (a type of white blood cell crucial for immunity). While individuals with ZAP70-SCID often have a normal or even elevated number of B cells (another type of white blood cell), these B cells do not function properly without functional T cell help. This leads to severe susceptibility to infections, similar to other forms of SCID. The disease is caused by mutations in the ZAP70 gene, which is vital for T-cell receptor signaling.
Symptoms
Symptoms of ZAP70-SCID are similar to other forms of SCID and typically appear in infancy. These include:
Recurrent, severe infections (e.g., pneumonia, sepsis, meningitis)
Failure to thrive (poor growth and weight gain)
Chronic diarrhea
Skin rashes (eczema-like)
Oral thrush (Candida infection)
Pneumocystis pneumonia (PCP)
Opportunistic infections (infections caused by organisms that typically don't affect healthy individuals)
Causes
ZAP70-SCID is caused by mutations in the ZAP70 gene. This gene provides instructions for making a protein called zeta-chain-associated protein kinase 70 (ZAP-70). This protein is crucial for T-cell receptor (TCR) signaling, which is essential for T-cell development and activation. Mutations in the *ZAP70* gene lead to a deficiency or dysfunction of the ZAP-70 protein, disrupting T-cell development and function, resulting in immunodeficiency. It is inherited in an autosomal recessive manner, meaning that both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
The primary treatment for ZAP70-SCID aims to restore immune function.
Hematopoietic Stem Cell Transplantation (HSCT): This is the most effective treatment. A healthy donor's stem cells replace the patient's defective immune system cells.
Gene Therapy: While still experimental, gene therapy involves inserting a normal copy of the ZAP70 gene into the patient's cells.
Intravenous Immunoglobulin (IVIG): This provides temporary passive immunity by supplying antibodies to help fight infections. It is used as a supportive therapy, particularly before HSCT or gene therapy.
Prophylactic Antibiotics and Antifungals: Used to prevent infections, especially Pneumocystis jirovecii pneumonia.
Supportive Care: This includes nutritional support, treatment of infections, and management of complications.
Is Communicable
ZAP70-SCID itself is not communicable. It is a genetic disorder caused by inherited gene mutations, not by an infectious agent. However, individuals with ZAP70-SCID are highly susceptible to communicable diseases due to their weakened immune system.
Precautions
For individuals with ZAP70-SCID, the following precautions are crucial:
Strict Isolation: Minimize exposure to potential sources of infection.
Hand Hygiene: Frequent and thorough handwashing is essential.
Avoid Crowds: Avoid crowded places, especially during outbreaks of respiratory illnesses.
Vaccinations: Live vaccines are contraindicated (harmful) due to the risk of overwhelming infection. Inactivated or subunit vaccines might provide some protection, but their effectiveness may be limited. The family members of the affected child should all receive live vaccines to reduce spread from healthy individuals.
Prophylactic Medications: Take prescribed prophylactic antibiotics and antifungals.
Monitor for Signs of Infection: Be vigilant for any signs of infection (fever, cough, diarrhea, etc.) and seek prompt medical attention.
Washed Food: All food must be cleaned before consumption.
Bottled water: All water consumed should be bottled.
How long does an outbreak last?
An "outbreak" in the context of ZAP70-SCID refers to an infection the individual contracts. The duration of an infection outbreak in a person with ZAP70-SCID depends on:
The specific infection.
The severity of the immunodeficiency.
The effectiveness of treatment.
The presence of any complications. Without treatment (HSCT or gene therapy), infections can become chronic and recurrent, leading to a persistently weakened state. With successful treatment, the frequency and severity of infections should decrease over time.
How is it diagnosed?
Diagnosis of ZAP70-SCID typically involves:
Newborn Screening: Many states include SCID in their newborn screening programs, which can detect T-cell lymphopenia (low T-cell count) using a TREC (T-cell receptor excision circle) assay. A low TREC result requires further investigation.
Complete Blood Count (CBC) with Differential: Shows the number and types of blood cells. In ZAP70-SCID, the T-cell count will be low or absent, but the B-cell count may be normal or elevated.
Lymphocyte Phenotyping: Flow cytometry is used to identify and quantify different types of immune cells. This will show a severe deficiency of CD8+ T cells and a normal or reduced number of CD4+ T cells that are non-functional.
T-Cell Function Assays: Assess the ability of T cells to proliferate and respond to stimulation. T cells from individuals with ZAP70-SCID will show impaired function.
Genetic Testing: Confirms the diagnosis by identifying mutations in the ZAP70 gene.
Family History: A family history of SCID or other immune deficiencies can raise suspicion.
Timeline of Symptoms
The timeline of symptoms in ZAP70-SCID typically follows this pattern:
Birth to 3 Months: Often asymptomatic at birth due to maternal antibodies. However, susceptibility to infections begins to increase as maternal antibodies wane.
3 to 6 Months: Onset of recurrent infections, failure to thrive, chronic diarrhea, and skin rashes.
6 Months and Beyond: Progression of infections, potentially leading to severe complications such as pneumonia, sepsis, meningitis, and opportunistic infections. Without treatment, the condition is usually fatal in the first one to two years of life.
Post-Treatment: After successful HSCT or gene therapy, immune function gradually improves, and the frequency and severity of infections decrease over time. However, immune reconstitution may take several months or even years.
Important Considerations
Early Diagnosis and Treatment: Early diagnosis through newborn screening and prompt treatment with HSCT or gene therapy are crucial for improving outcomes.
Genetic Counseling: Genetic counseling is recommended for families with a history of ZAP70-SCID to assess the risk of recurrence and discuss reproductive options.
Long-Term Follow-Up: Even after successful treatment, individuals with ZAP70-SCID require long-term follow-up to monitor immune function, manage potential complications (e.g., graft-versus-host disease after HSCT), and provide ongoing support.
Psychosocial Support: Families affected by ZAP70-SCID face significant emotional and practical challenges. Psychosocial support and access to resources are essential.
Research: Ongoing research is aimed at improving diagnostic methods, treatment strategies, and long-term outcomes for individuals with ZAP70-SCID.