Severe combined immunodeficiency (SCID) represents a group of rare, sometimes fatal, congenital disorders characterized by little or no immune response.
The defining feature of SCID, commonly known as "bubble boy" disease, is a defect in the specialized white blood cells (B- and T-lymphocytes) that defend us from infection by viruses, bacteria and fungi.
There are several forms of SCID. The most common type is linked to the X chromosome, making this form affect only males. Other forms of SCID usually follow an autosomal recessive inheritance pattern or are the result of spontaneous mutations. One of these other forms is linked to a deficiency of the enzyme adenosine deaminase (ADA). Other cases of SCID are caused by a variety of other defects.
Classic signs of SCID include an increased susceptibility to infection and failure to thrive as a result of infections. A baby with SCID may have recurrent bacterial, viral, or fungal infections that are much more serious and less responsive to treatment than would normally be expected. These can include ear infections (acute otitis media), sinus infections (sinusitis), oral thrush (a type of yeast infection in the mouth), skin infections, meningitis, and pneumonia. Infants with SCID may also have chronic diarrhea. If a child has these symptoms, a doctor will test for SCID or other types of immune deficiency.
The most common treatment for SCID is (a sibling is generally best). David Vetter, the original "bubble boy", had one of the first transplantations, and finally 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.
More recently, gene therapy has proved useful. 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 three of eleven patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. 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.
