Severe combined immunodeficiency

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Overview
Severe combined immunodeficiency, or Boy in the Bubble Syndrome, 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. The most famous case is the boy David Vetter.

Chronic diarrhea, ear infections, recurrent Pneumocystis jirovecii pneumonia, and profuse oral candidiasis commonly occur. These babies, if untreated, usually die within 1 year due to severe, recurrent infections. However, treatment options are much improved since David Vetter.

Prevalence
Classical SCID has a reported incidence of about 1 in 65,000 live births in Australia.

Recent studies indicate that one in every 2,500 children in the Navajo population inherit severe combined immunodeficiency. This condition is a significant cause of illness and death among Navajo children. Ongoing research reveals a similar genetic pattern among the related Apache people.

Detection
Standard testing of SCID is not currently available for newborns due to the diversity of the genetic defect. Some 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 because newborns carry their mother's antibodies for the first few weeks of life and SCID babies look normal.

Treatment
The most common treatment for SCID is bone marrow transplantation, which has been successful using either a matched donor (a sibling is generally best)or a half-matched donor, who would be either parent. The half-matched type of transplant is called haplo-identical and was perfected by Memorial Sloan Kettering Cancer Center in New York and also Duke University Medical Center which currently does the highest number of these transplants of any center in the world. David Vetter, the original "bubble boy", had one of the first transplantations but eventually died because of an unscreened virus, Epstein-Barr (tests were not available at the time), in his newly transplanted bone marrow from his sister. Today, transplants done in the first three months of life have a high success rate. Physicians have also had some success with in utero transplants done before the child is born and also by using cord blood which is rich in stem cells.

More recently gene therapy has been attempted as an alternative to the bone marrow transplant. Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID. The first gene therapy trials were performed in 1990, with peripheral T cells. In 2000, the first gene therapy "success" resulted in SCID patients with a functional immune system. These trials were stopped when it was discovered that two of ten patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. In 2007, four of the ten patients have developed leukemias. Work is now focusing on correcting the gene without triggering an oncogene. No leukemia cases have yet been seen in trials of ADA-SCID, which does not involve the gamma c gene that may be oncogenic when expressed by a retrovirus.

Trial treatments of SCID have been gene therapy's only success; since 1999, gene therapy has restored the immune systems of at least 17 children with two forms (ADA-SCID and X-SCID) of the disorder.