Severe combined immune deficiency

Severe Combined Immune Deficiency
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Increased susceptibility to infections
Complications	Infections, autoimmune disorders
Onset	Infancy
Duration	Lifelong
Types	N/A
Causes	Genetic mutations
Risks	Family history
Diagnosis	Genetic testing, blood tests
Differential diagnosis	N/A
Prevention	N/A
Treatment	Bone marrow transplant, gene therapy
Medication	N/A
Prognosis	Variable
Frequency	Rare
Deaths	N/A

Severe Combined Immune Deficiency (SCID) is a rare, life-threatening genetic disorder characterized by a severely compromised immune system. Individuals with SCID are highly susceptible to infections due to the absence or dysfunction of T cells and B cells, which are critical components of the adaptive immune response.

Etiology

SCID is caused by mutations in genes that are essential for the development and function of lymphocytes. The most common form of SCID is X-linked SCID, which is caused by mutations in the IL2RG gene located on the X chromosome. Other forms of SCID can result from mutations in genes such as ADA, RAG1, RAG2, and JAK3.

Genetic Mutations

• X-linked SCID: Caused by mutations in the IL2RG gene, leading to a lack of functional interleukin-2 receptor gamma chain, which is crucial for lymphocyte signaling.
• Adenosine Deaminase Deficiency (ADA-SCID): Results from mutations in the ADA gene, leading to toxic accumulation of metabolites that are harmful to lymphocytes.
• RAG1/RAG2 Deficiency: Mutations in these genes impair the recombination of antigen receptor genes, preventing the development of functional T and B cells.

Pathophysiology

In SCID, the immune system's ability to fight off infections is severely impaired due to the absence or dysfunction of T and B lymphocytes. This leads to:

• Lack of cell-mediated immunity, as T cells are crucial for recognizing and responding to infected cells.
• Impaired humoral immunity, as B cells are responsible for producing antibodies.
• Increased susceptibility to opportunistic infections, including bacterial, viral, and fungal pathogens.

Clinical Presentation

Infants with SCID typically present within the first few months of life with recurrent, severe infections. Common clinical features include:

• Chronic diarrhea
• Failure to thrive
• Recurrent pneumonia
• Oral thrush
• Skin rashes

Diagnosis

Early diagnosis of SCID is critical for effective management. Diagnostic approaches include:

• Newborn screening: Detects low levels of T-cell receptor excision circles (TRECs) in dried blood spots.
• Genetic testing: Identifies specific mutations associated with SCID.
• Flow cytometry: Assesses the presence and function of T, B, and NK cells in the blood.

Management

The primary treatment for SCID is hematopoietic stem cell transplantation (HSCT), which can restore immune function. Other treatment options include:

• Gene therapy: Experimental approach that involves correcting the genetic defect in the patient's own hematopoietic stem cells.
• Enzyme replacement therapy: Used in ADA-SCID to provide the missing enzyme.
• Prophylactic antibiotics and antifungals: To prevent infections.
• Immunoglobulin replacement therapy: Provides passive immunity by supplying antibodies.

Prognosis

The prognosis for individuals with SCID varies depending on the type of SCID, the timing of diagnosis, and the success of treatment. Early diagnosis and treatment, particularly with HSCT, significantly improve outcomes.

Epidemiology

SCID is a rare disorder, with an estimated incidence of 1 in 50,000 to 100,000 live births. It affects both males and females, although X-linked SCID is more common in males due to its inheritance pattern.

See Also

• Primary immunodeficiency
• Bone marrow transplant
• Gene therapy

External Links

• NIAID - Severe Combined Immunodeficiency
• SCID.net