Summary about Disease
ZAP-70-related severe combined immunodeficiency (ZAP-70-SCID) is a rare genetic disorder that affects the immune system. Specifically, it impairs the development and function of T cells, a type of white blood cell critical for fighting off infections. Individuals with ZAP-70-SCID are highly susceptible to severe and recurrent infections from an early age. However, B cell function is usually normal.
Symptoms
Recurrent and severe infections, such as pneumonia, sepsis, meningitis, and chronic diarrhea.
Failure to thrive (poor growth and weight gain).
Skin rashes (eczema).
Oral thrush (fungal infection in the mouth).
Enlarged liver and spleen (hepatosplenomegaly).
Causes
ZAP-70-SCID is caused by mutations in the ZAP70 gene. This gene provides instructions for making the ZAP-70 protein, which is essential for T cell signaling and development. Mutations in the gene lead to a non-functional or absent ZAP-70 protein, disrupting T cell maturation and function. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Antibiotics, antivirals, and antifungals: Used to treat and prevent infections.
Intravenous immunoglobulin (IVIG): Provides temporary passive immunity by supplying antibodies from healthy donors.
Hematopoietic stem cell transplantation (HSCT): A potentially curative treatment that involves replacing the patient's defective immune system with healthy stem cells from a donor.
Gene therapy: Experimental but shows promise for correcting the genetic defect.
Is Communicable
ZAP-70-SCID itself is not communicable. It is a genetic disorder and cannot be spread from person to person. However, individuals with ZAP-70-SCID are highly susceptible to communicable diseases (infections) due to their weakened immune system.
Precautions
Strict hygiene: Frequent handwashing, avoiding contact with sick individuals.
Prophylactic antibiotics, antivirals, or antifungals: To prevent opportunistic infections.
Avoiding live vaccines: Because the immune system cannot mount an appropriate response, live vaccines can cause serious illness.
Isolation: In some cases, protective isolation may be necessary to minimize exposure to pathogens.
How long does an outbreak last?
There are no "outbreaks" of ZAP-70-SCID, as it is not an infectious disease. However, a person with ZAP-70-SCID can experience recurrent infections, and the duration of each infection will vary depending on the pathogen, the severity of the infection, and the effectiveness of treatment. Without treatment, infections can be chronic and life-threatening.
How is it diagnosed?
Newborn screening: Some regions include SCID in their newborn screening programs, which detects low T cell receptor excision circles (TRECs).
Complete blood count (CBC) with lymphocyte subset analysis: Reveals low or absent T cells, specifically CD8+ T cells, while CD4+ T cells may be present but non-functional.
T cell function tests: Demonstrates impaired T cell activation and proliferation.
ZAP-70 protein expression analysis: Assesses the presence and amount of ZAP-70 protein in T cells.
Genetic testing: Confirms the diagnosis by identifying mutations in the ZAP70 gene.
Timeline of Symptoms
Early infancy (first few months of life): Onset of recurrent infections, failure to thrive, diarrhea, and skin rashes.
Without treatment: Infections become increasingly severe and frequent, leading to life-threatening complications.
With treatment (IVIG and prophylactic medications): Infections may be controlled to some extent, but the underlying immune deficiency persists.
After HSCT: Immune reconstitution may occur, leading to improved immune function and reduced susceptibility to infections. The timeline for immune reconstitution varies.
Important Considerations
Early diagnosis and treatment are crucial for improving outcomes.
HSCT is the preferred curative treatment, but finding a suitable donor can be challenging.
Long-term monitoring and management are necessary, even after successful HSCT, to detect and manage potential complications.
Genetic counseling is recommended for families with a history of ZAP-70-SCID.