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Severe Combined Immune Deficiency

Types And Severity Of Immunodeficiency Diseases, Scid, Gene Therapy

The development of the immune system is a very complicated process. Stem cells in the bone marrow continually give rise to the white blood cells responsible for producing antibodies (B-lymphocytes), recognizing and destroying foreign cells (T-lymphocytes) and performing immune surveillance for cancer and foreign cells. Immunodeficiency results when the normal complex interactions of the immune system required to do this fail, resulting in susceptibility to infections or cancer.


This gene is currently the only known X-linked version of SCID (all other SCID forms identified are autosomal and recessive). SCID-X1 accounts for 46 percent of all SCID cases and exhibits a high spontaneous mutation rate. It is caused by mutations in the gene for the γ subunit of the interleukin 2 (IL-2) cytokine receptor. This receptor is part of a critical cytokine signal pathway required early in immune system growth and differentiation. The most famous SCID-X1 patient was David Vetter. Known as the "bubble boy," he lived for twelve years in an isolated environment before dying from an Epstein-Barr virus infection.


This occurs in 15 percent of SCID patients. It is due to mutation in the ADA gene on chromosome 20. In the absence of ADA enzyme, accumulation of deoxyATP (a DNA nucleotide) occurs within immune cell precursors. This leads to their death through apoptosis within six months of birth. Unlike other forms of SCID, ADA-SCID patients can be treated through enzyme replacement therapy. Weekly injections of ADA enzyme (stabilized with polyethylene glycol) hinders toxic deoxyATP buildup, reducing apoptosis and permitting some B-and T-lymphocytes to mature. However, bone marrow transplantation provides better immunity if it succeeds.

JAK3 Deficiency.

This accounts for 7 percent of SCID patients. This form of SCID maps to the Janus kinase 3 gene on chromosome 19. JAK3 enzyme, a tyrosine kinase, is part of the intracellular signaling pathway (JAK-STAT) Baby David ("bubble boy") Vetter plays in his plastic-enclosed environment. This protection helped David to survive, since he was born with severe combined immune deficiency syndrome. that activates the genes for T-lymphocyte differentiation. To do so, it must bind to the SCID-X1 gene product.

Interleukin-7 receptor α Chain Deficiency.

This is responsible for SCID in a small number of patients. This receptor is part of a larger complex that includes the SCID-X1, JAK3 proteins, and four other interleukin receptors (IL-2, IL-5, IL-9 and IL-15). Thus, at least three of the known SCID genes have been found to disrupt the same receptor complex involved in immune system development.

RAG1 and 2 Deficiencies.

These can also lead to SCID. RAG1 and RAG2 are found side-by-side on chromosome 6. Mutations in either can result in SCID. They are involved in the genetic rearrangement of both the T- and B-lymphocyte receptor genes during differentiation that gives rise to the ability of the immune system to recognize foreign agents. Mutations in RAG1 or 2 also account for 50 percent of those patients with an unusual autoimmunity form of SCID called Omenn syndrome.

The genes involved in two additional rare forms of SCID, reticular dysgenesis and cartilage-hair hypoplasia, remain unknown. In addition, the gene(s) for over 30 percent of those patients diagnosed with SCID also remain unidentified, even though these patients seem to display the same phenotypes as those patients whose genetic defect has been identified.

Additional topics

Medicine EncyclopediaGenetics in Medicine - Part 4