Bubble Boy Disease

Other Names: Severe combined immunodeficiency (SCID), or Boy in the Bubble Syndrome, (also known as “Alymphocytosis,” “Glanzmann–Riniker syndrome,” “Severe mixed immunodeficiency syndrome,” and “Thymic alymphoplasia”


Definition:

It 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 some of them, such as David Vetter, become famous for living in a sterile environment.

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David Vetter poses inside of his bubble in his Houston home in this Dec. 17, 1976

The body’s immune system fights against diseases and infections. The SCID syndromes are inherited disorders that result in severe defects in the immune system. White blood cells (which fight infection) are produced in the bone marrow by stem cells. In people with SCID, the bone marrow stem cells are absent or defective. This leaves the affected person open to any and all germs around him because he has no way to fight them off.

Prevalence:-
The most commonly quoted figure for the prevalence of SCID is around 1 in 100,000 births, although this is regarded by some to be an underestimate of the true prevalence; and a figure of about 1 in 65,000 live births has been reported for 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.

Types
:-
1. X-linked severe combined immunodeficiency:

Most cases of SCID are due to mutations in the gene encoding the common gamma chain (?c), a protein that is shared by the receptors for interleukins IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. These interleukins and their receptors are involved in the development and differentiation of T and B cells. Because the common gamma chain is shared by many interleukin receptors, mutations that result in a non-functional common gamma chain cause widespread defects in interleukin signalling. The result is a near complete failure of the immune system to develop and function, with low or absent T cells and NK cells and non-functional B cells.
The common gamma chain is encoded by the gene IL-2 receptor gamma, or IL-2R?, which is located on the X-chromosome. Therefore, immunodeficiency caused by mutations in IL-2R? is known as X-linked severe combined immunodeficiency. The condition is inherited in an X-linked recessive pattern.


2.Adenosine deaminase deficiency:-

The second most common form of SCID after X-SCID is caused by a defective enzyme, adenosine deaminase (ADA), necessary for the breakdown of purines. Lack of ADA causes accumulation of dATP. This metabolite will inhibit the activity of ribonucleotide reductase, the enzyme that reduces ribonucleotides to generate deoxyribonucleotides. The effectiveness of the immune system depends upon lymphocyte proliferation and hence dNTP synthesis. Without functional ribonucleotide reductase, lymphocyte proliferation is inhibited and the immune system is compromised.

3. Omenn syndrome:

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 V(D)J recombination, the process by which segments 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 V(D)J recombination, causing SCID.

4.Bare lymphocyte syndrome:-

MHC class II is not expressed on the cell surface of all antigen presenting cells. Autosomal recessive. The MHC-II gene regulatory proteins are what is altered, not the MHC-II protein itself.

5.JAK3 :-  Janus kinase-3 (JAK3) is an enzyme that mediates transduction downstream of the ?c signal. Mutation of its gene also causes SCID.

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6.Artemis/DCLRE1C:-
Mortan Cowan, MD, director of the Pediatric Bone Marrow Transplant Program at the University of California-San Francisco, noted that although researchers have identified about a dozen genes that cause SCID, the Navajo and Apache population has the most severe form of the disorder. This is due to the lack of a gene designated Artemis. Without the gene, children’s bodies are unable to repair DNA or develop disease-fighting cells.


Symptoms:

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.


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The list of signs and symptoms mentioned in various sources for SCID includes the 35 symptoms listed below:

Causes
:
Click to see :New Genetic Cause Of Boy In The Bubble Syndrome :

New gene mutation found to cause ‘bubble boy disease’ :


How Gene Defects Cause Disease :


Diagnosis:

Several US states are performing pilot studies to diagnose SCID in newborns through the use of T-cell recombinant excision circles.[citation needed] Wisconsin and Massachusetts (as of February 1, 2009) screen newborns for SCID.

Despite these pilot programs, standard testing for SCID is not currently available in 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 diagnosed 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.

You may click to see :Diagnostic Tests for SCID :

Treatment
:-
The most common treatment for SCID is bone marrow transplantation, which has been successful using either a matched related or unrelated donor, or a half-matched donor, who would be either parent. The half-matched type of transplant is called haploidentical 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. In 1990, 12-year-old Ashanthi DeSilva became the first patient to undergo successful gene therapy. Researchers collected samples of Ashanthi’s blood, isolated some of her white blood peripheral T cells, and incorporated into them a virus engineered to contain a healthy immune system enzyme: adenosine deaminase (ADA) gene. These cells were then injected back into her body. She is now given a weekly shot of ADA that without would have her destined for a life of isolation. 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 [11]. 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.

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Drugs and Medications used to treat SCID:
A new hope for gene therapy

Breakthrough for “Bubble Boy” Disease

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:

http://en.wikipedia.org/wiki/Severe_combined_immunodeficiency#cite_note-Bolognia-0
http://rarediseases.about.com/od/immunedisorders/a/scid.htm
http://www.wrongdiagnosis.com/s/scid/intro.htm

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