Summary about Disease
ZAP70 deficiency is a rare primary immunodeficiency characterized by a lack of functional ZAP70 protein in T cells. This deficiency primarily affects T cell development and function, leading to severe combined immunodeficiency (SCID)-like symptoms. Individuals with ZAP70 deficiency are particularly susceptible to opportunistic infections due to impaired T cell-mediated immunity, while B cell and NK cell numbers are generally normal.
Symptoms
Severe, recurrent infections (e.g., pneumonia, sepsis, fungal infections, viral infections).
Failure to thrive.
Diarrhea.
Skin rashes (eczema).
Lymphadenopathy (enlarged lymph nodes).
Hepatosplenomegaly (enlarged liver and spleen).
Opportunistic infections, such as Pneumocystis pneumonia or disseminated BCG (Bacille Calmette-Guérin) infection if vaccinated.
Causes
ZAP70 deficiency is caused by mutations in the ZAP70 gene. This gene provides instructions for making the ZAP70 protein, which is essential for T cell receptor (TCR) signaling during T cell development and activation. Mutations in the *ZAP70* gene result in a non-functional or absent ZAP70 protein, disrupting T cell development and function. It is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the condition.
Medicine Used
Hematopoietic stem cell transplantation (HSCT): HSCT is the only curative treatment for ZAP70 deficiency. It replaces the patient's immune system with healthy immune cells from a donor.
Intravenous immunoglobulin (IVIG): IVIG provides temporary passive immunity by supplying antibodies to help fight infections.
Antibiotics, antifungals, and antivirals: These medications are used to treat and prevent infections.
Prophylactic antibiotics/antifungals: These are used preventatively to reduce the risk of infection.
Supportive care: Nutritional support and other measures to manage symptoms.
Is Communicable
No, ZAP70 deficiency is not communicable. It is a genetic disorder caused by a mutation in the ZAP70 gene and cannot be transmitted from person to person.
Precautions
Strict hygiene: Frequent handwashing and avoiding contact with sick individuals.
Prophylactic medications: Administering prophylactic antibiotics and antifungals to prevent infections.
Avoidance of live vaccines: Live vaccines can cause serious infections in individuals with ZAP70 deficiency.
Irradiated blood products: If blood transfusions are necessary, irradiated blood products should be used to prevent graft-versus-host disease.
Isolation: In some cases, isolation may be necessary to protect the patient from exposure to pathogens.
Genetic counseling: For families with a history of ZAP70 deficiency, genetic counseling is recommended to assess the risk of recurrence in future pregnancies.
How long does an outbreak last?
ZAP70 deficiency itself is not an outbreak. It is a chronic genetic condition. The infections that individuals with ZAP70 deficiency experience can last for varying durations, depending on the specific pathogen, the severity of the infection, and the effectiveness of treatment. Without immune reconstitution (through HSCT), these individuals remain susceptible to recurrent and chronic infections throughout their lives.
How is it diagnosed?
Lymphocyte phenotyping: Blood test to evaluate the number and types of lymphocytes (T cells, B cells, NK cells). Characteristically, individuals with ZAP70 deficiency will have normal or near-normal numbers of CD8+ T cells, but very few CD4+ T cells that express the T cell receptor (TCR). CD4+ T cells are present, but lack the ability to signal properly.
T cell function testing: Assesses the ability of T cells to proliferate and produce cytokines in response to stimulation. T cells from ZAP70-deficient individuals will show impaired or absent function.
ZAP70 protein expression: Measures the level of ZAP70 protein in T cells via flow cytometry. In ZAP70 deficiency, ZAP70 protein will be absent or significantly reduced.
Genetic testing: Confirms the diagnosis by identifying mutations in the ZAP70 gene.
Newborn screening: SCID newborn screening may identify ZAP70 deficiency through TREC (T-cell receptor excision circle) analysis.
Timeline of Symptoms
Symptoms typically begin in infancy or early childhood, often within the first few months of life. The timeline can vary between individuals, but the general progression often involves:
Early infancy: Failure to thrive, diarrhea, skin rashes.
First few months: Recurrent and severe infections, such as pneumonia or sepsis.
Ongoing: Continued susceptibility to opportunistic infections and chronic health problems without treatment.
If Untreated: Increased risk of death in early childhood.
Important Considerations
Early diagnosis is critical: Early diagnosis and treatment (HSCT) are essential to improve outcomes and prevent life-threatening infections.
HSCT is the curative treatment: HSCT can restore immune function and significantly improve the quality of life for individuals with ZAP70 deficiency.
Lifelong monitoring: Even after HSCT, lifelong monitoring is necessary to detect and manage potential complications, such as graft-versus-host disease or secondary immunodeficiencies.
Family screening: If a child is diagnosed with ZAP70 deficiency, it is important to screen siblings and other family members to identify potential carriers of the ZAP70 gene mutation.
Psychosocial support: Families affected by ZAP70 deficiency require psychosocial support to cope with the challenges of a rare and serious genetic disorder.