Summary about Disease
X-linked severe combined immunodeficiency (X-linked SCID), also known as SCID1, is a rare genetic disorder characterized by the absence or severely dysfunctional T cells and natural killer (NK) cells, which are critical components of the immune system. This deficiency makes individuals extremely vulnerable to severe and life-threatening infections from bacteria, viruses, and fungi. Because of this severe immune deficiency, individuals with X-linked SCID can not survive without a bone marrow transplant or gene therapy. X-linked SCID is caused by mutations in the IL2RG gene, located on the X chromosome.
Symptoms
Frequent and severe infections, often starting in early infancy (e.g., pneumonia, sepsis, meningitis)
Failure to thrive (poor weight gain and growth)
Chronic diarrhea
Skin rashes (eczema)
Oral thrush (candidiasis)
Absence of tonsils and lymph nodes
Pneumocystis pneumonia (PCP) is a common initial infection.
Causes
X-linked SCID is caused by mutations in the IL2RG gene, which encodes the interleukin-2 receptor gamma chain (also known as CD132). This protein is a component of several cytokine receptors crucial for the development and function of T cells, NK cells, and some B cells. Mutations in *IL2RG* disrupt the signaling pathways essential for these immune cells to mature and function properly. Because the *IL2RG* gene is located on the X chromosome, males are predominantly affected. Females can be carriers of the mutation, typically without exhibiting symptoms.
Medicine Used
Prophylactic antibiotics: To prevent bacterial infections.
Antifungal medications: To prevent fungal infections, like PCP.
Antiviral medications: To prevent viral infections.
Intravenous immunoglobulin (IVIG): Provides passive immunity by supplying antibodies from healthy donors.
Bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT): To replace the defective immune system with a healthy one.
Gene therapy: Using a viral vector to deliver a functional copy of the IL2RG gene into the patient's cells.
Is Communicable
X-linked SCID itself is not communicable. It is a genetic disorder, not an infectious disease. However, individuals with X-linked SCID are highly susceptible to infections that are communicable.
Precautions
Strict hygiene: Frequent handwashing, avoiding contact with sick individuals.
Protective isolation: Keeping the infant/child in a controlled environment to minimize exposure to pathogens.
Avoidance of live vaccines: Because the immune system is severely compromised, live vaccines can cause serious infections.
Prophylactic medications: As prescribed by the physician to prevent common infections.
Cook all food thoroughly, and filter drinking water: To eliminate the possibility of food or waterborne infectious agents.
How long does an outbreak last?
X-linked SCID is not an outbreak-related disease. It is a chronic condition that lasts a lifetime if untreated. Infections in individuals with X-linked SCID can be prolonged and severe due to their immune deficiency.
How is it diagnosed?
Newborn screening: Many regions now include SCID in newborn screening programs, using a T-cell receptor excision circle (TREC) assay to detect a lack of T cells.
Complete blood count (CBC) with differential: Shows low lymphocyte counts.
Immunoglobulin levels: Typically low or absent.
T cell subset analysis: Demonstrates the absence or severe reduction of T cells.
Lymphocyte proliferation assays: Assess the ability of lymphocytes to respond to stimulation.
Genetic testing: Confirms the diagnosis by identifying mutations in the IL2RG gene.
Timeline of Symptoms
Birth: Usually no obvious symptoms at birth.
First few months: Onset of recurrent infections (e.g., pneumonia, diarrhea, thrush), failure to thrive.
Without treatment: Infections become increasingly severe and life-threatening within the first year of life.
Important Considerations
Early diagnosis is critical: Newborn screening is essential for timely intervention.
Prompt treatment is life-saving: Bone marrow transplantation or gene therapy should be considered as soon as possible.
Genetic counseling: Important for families with a history of X-linked SCID.
Long-term monitoring: Even after successful treatment, individuals require ongoing monitoring for immune function and potential complications.
Family support: Coping with a rare and serious condition requires significant support for the affected child and family.