Severe combined immunodeficiency
Severe Combined Immunodeficiency, or SCID, is a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune system are crippled, due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency. It is also known as the "bubble boy" disease because its victims are extremely vulnerable to infectious diseases and must live (if untreated) in a completely sterile environment. The most famous case is the boy David Vetter. more...
SCID affects about 1 in 80,000 live births. These babies, if untreated, usually die within 1 year due to severe, recurrent infections. Chronic diarrhea, ear infections, recurrent Pneumocystis jiroveci pneumonia, and profuse oral candidiasis commonly occur. Treatment options are much improved since David Vetter, and living in a bubble is no longer necessary.
IL-7 signalling pathway
Most cases of SCID are derived from mutations in the γc chain in the receptors for interleukins IL-2, IL-4, IL-7, IL-9 and IL-15. These interleukins and their receptors are involved in the development and differentiation of T and B cells. Deleterious mutations in the gamma-chain or in the JAK3 protein cause a form of SCID that is characterized by low numbers of T and NK cells, and presence of non-functional B cells.
The IL-2 receptor γ (IL-2Rγ) gene is located on the X chromosome and mutation of this gene causes X-linked SCID.
Janus kinase-3 (JAK3) is an enzyme that mediates transduction downstream of the γc signal. Mutation of its gene also causes SCID.
The manufacture of immunoglobulins requires recombinase enzymes derived from the recombination activating genes RAG-1 and RAG-2. These enzymes are involved in the first stage of VDJ recombination, the process by which segements of a B cell or T cell's DNA are rearranged to create a new T cell receptor or B cell receptor (and, in the B cell's case, the template for antibodies). Certain mutations of the RAG-1 or RAG-2 genes prevent VDJ recombination, causing SCID.
Another well-known form of SCID is caused by a defective enzyme, adenosine deaminase (ADA), necessary for the breakdown of purines. Lack of ADA causes accumulation of dGTP. This metabolite is toxic to lymphoid stem cells.
Standard testing of SCID is not performed for newborns due to the rarity of the disease and the cost of the testing. SCID can be detected by sequencing fetal DNA if a known history of the disease exists. Otherwise, SCID is not detected until about six months of age, usually indicated by recurrent infections. The delay in detection is due to the fact that newborns carry their mother's antibodies for the first few weeks of life and have not yet been exposed to any diseases.
The most common treatment for SCID is bone marrow transplantation, which requires matched donors (a sibling is generally best). David Vetter, the original "bubble boy," endured several failed transplantations, and finally passed away because of an unscreened virus, Epstein-Barr, in his newly-transplanted bone marrow from his sister. Today, transplants done in the first three months of life have a high success rate.
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