Severe combined immunodeficiency

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Severe Combined Immunodeficiency

Severe combined immunodeficiency

Definition

Severe combined immunodeficiency (SCID) is the most serious primary or congenital human immunodeficiency disorder. It is a group of congenital (present from birth) disorders in which the immune system does not work properly. Children with SCID are vulnerable to recurrent severe infections, retarded growth, and early death.

Description

The immune system is composed of elements that are needed for the body to fight infections by recognizing disease agents and attacking them. It includes many classes of T-lymphocytes (white blood cells that detect foreign proteins called antigens). It also includes B cells, which are the only cells in the body that make antibodies. Natural killer (NK) cells are cells that destroy infected cells. In children with SCID, the immune system does not function properly because T, B, and NK cells are either absent or defective. When the immune system does not function correctly, the child is left open to repeated severe diseases and infections.

Several different immune system disorders are grouped under SCID. These include the following:

  • X-linked: The most common form of SCID accounts for about half of all cases. Because this is an X-linked condition, it occurs only in boys. Children with X-linked SCID have low T-cell and natural killer (NK) cell levels but elevated B-cell levels.
  • Adenosine deaminase deficiency (ADA): About 20 percent of SCID cases are of this type. ADA deficiency leads to low levels of B and T cells in the child's immune system.
  • Janus Kinase 3 (Jak3) deficiency: This form of SCID accounts for about 6 percent of cases. There are very low levels of T and NK cells, or they are not present at all. There is an elevated level of B cells. In this form of SCID the lymphocyte or white blood evaluation is identical to X-linked SCID but is autosomal recessive and, therefore, occurs in girls and boys.

Demographics

The rate of SCID is not perfectly documented. It is estimated that it occurs in between one in 50,000 and one in 500,000 infants. It is about three times more common in boys than in girls.

Causes and symptoms

SCID is an inherited disorder. In all forms of SCID, B and T cells are non-functioning. They may or may not be present in various forms of SCID, but they are always non-functioning. In some forms of SCID, NK cells are also absent or non-funtioning.

For the first few months after birth, a infant with SCID is often protected by antibodies acquired before birth from the mother's blood. As early as three months of age, however, the SCID child begins to suffer from mouth infections (thrush), chronic diarrhea , otitis media , and pulmonary infections, including pneumocystis pneumonia . The child loses weight, becomes very weak, and if untreated eventually dies from an opportunistic infection.

When to call the doctor

If a child has unusual infections, unusually severe infections, infections with unusual organisms, or unusual complications of usual infections, a doctor should be consulted to evaluate for possible immune deficiency. This is particularly important if there is a family history of immune deficiency.

Diagnosis

The first screening test for SCID is a white blood cell count with a count of the lymphocytes (differential) because in most forms of SCID the lymphocyte count will be very low. Blood tests can then be done to test for the numbers of B, T, and NK type lymphocytes. If the numbers of all of these cell types are normal and SCID is still suspected, more specialized tests can be done to test the lymphocyte cell functions. Rarely there are children with SCID who have normal lymphocyte numbers and nonfunctioning cells.

Treatment

Patients with SCID should be treated aggressively with antibiotics for any infection, and intravenous immunoglobulin should be given to replace the antibiotics the children cannot make, but these treatments cannot cure the disorder. Bone marrow transplants are as of 2004 regarded as one of the few effective standard treatments for most types of SCID. For those children with ADA deficiency, ADA infusions are the accepted treatment of choice. Up to 95 percent of children who are treated with bone marrow transplants, especially those who are treated before three months of age, survive.

Investigational treatments

As an example of gene therapy for SCID children with ADA deficiency, the child receives periodic infusions of his or her own T cells corrected with a gene for ADA that has been implanted in an activated virus. This should allow these cells to function normally. Other types of SCID have been treated with gene therapy, but these procedures have been put on hold due to serious complications (malignancies). Researchers are as of 2004 also investigating treating SCID in the yet unborn fetus, which has been done successfully a few times.

Prognosis

There is no cure for SCID. Nearly all untreated patients die before age two, most before one year of age. Children who are treated with bone marrow transplants have a much better prognosis.

Prevention

There is no known way to prevent SCID. Genetic counseling is recommended for parents of a child with SCID who are considering having more children and for potential parents who have a family history of the disease and believe they may be carriers.

Parental concerns

Without prompt treatment SCID is nearly always fatal. Treatment can be very successful if done early, preferably within the first three months of life. Research is continuing into in utero treatment options, and some in utero treatments have been successfully carried out, so fetal screening may be helpful if there is a possibility that the child has SCID.

KEY TERMS

Adenosine deaminase (ADA) An enzyme that is lacking in a specific type of severe combined immunodeficiency disease (SCID). Children with an ADA deficiency have low levels of both B and T cells.

Antigen A substance (usually a protein) identified as foreign by the body's immune system, triggering the release of antibodies as part of the body's immune response.

Bcell A type of white blood cell derived from bone marrow. B cells are sometimes called B lymphocytes. They secrete antibodies and have a number of other complex functions within the human immune system.

Congenital Present at birth.

Gene therapy An experimental treatment for certain genetic disorders in which a abnormal gene is replaced with the normal copy. Also called somatic-cell gene therapy.

Lymphocyte A type of white blood cell that participates in the immune response. The two main groups are the B cells that have antibody molecules on their surface and T cells that destroy antigens.

T cell A type of white blood cell that is produced in the bone marrow and matured in the thymus gland. It helps to regulate the immune system's response to infections or malignancy.

Thrush An infection of the mouth, caused by the yeast Candida albicans and characterized by a whitish growth and ulcers.

Resources

BOOKS

Parker, James N., and Philip M. Parker. The Official Parent's Sourcebook on Primary Immunodeficiency. Red Hill, Australia: Icon Health, 2002.

ORGANIZATIONS

Immune Deficiency Foundation. 40 W. Chesapeake Avenue Suite 308, Towson, MD 21204. Web site: <www.primaryimmune.org>.

International Patient Organization for Patients with Primary Immunodeficiencies. Alliance House, 12 Caxton Street, London SW1H 0QS. Web site: <www.ipopi.org>

WEB SITES

Ballard, Barb. The SCID Homepage, September 2004. Available online at <www.scid.net/> (accessed November 14, 2004).

Tish Davidson, A.M. Rebecca J. Frey, PhD

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Davidson, Tish; Frey, Rebecca. "Severe Combined Immunodeficiency." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. 24 Jun. 2016 <http://www.encyclopedia.com>.

Davidson, Tish; Frey, Rebecca. "Severe Combined Immunodeficiency." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. (June 24, 2016). http://www.encyclopedia.com/doc/1G2-3447200511.html

Davidson, Tish; Frey, Rebecca. "Severe Combined Immunodeficiency." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Retrieved June 24, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3447200511.html

Severe Combined Immunodeficiency

Severe Combined Immunodeficiency

Definition

Severe combined immunodeficiency (SCID) is the most serious human immunodeficiency disorder(s). It is a group of congenital disorders in which both the humoral part of the patient's immune system and the cells involved in immune responses fail to work properly. Children with SCID are vulnerable to recurrent severe infections, retarded growth, and early death.

Description

SCID is thought to affect between one in every 100,000 persons, and one in every 500,000 infants. Several different immune system disorders are currently grouped under SCID:

  • Swiss-type agammaglobulinemia. This was the first type of SCID discovered, in Switzerland in the 1950s.
  • Adenosine deaminase deficiency (ADA). About 50% of SCID cases are of this type. ADA deficiency leads to low levels of B and T cells in the child's immune system.
  • Autosomal recessive. About 40% of SCID cases are inherited from the parents in an autosomal recessive pattern.
  • Bare lymphocyte syndrome. In this form of SCID, the white blood cells (lymphocytes) in the baby's blood are missing certain proteins. Without these proteins, the lymphocytes cannot activate the T cells in the immune system.
  • SCID with leukopenia. Children with this form of SCID are lacking a type of white blood cell called a granulocyte.

In order to understand why SCID is considered the most severe immunodeficiency disorder, it is helpful to have an outline of the parts of the human immune system. It has three parts: cellular, humoral, and nonspecific. The cellular and humoral parts of the system are both needed to fight infections-they recognize disease agents and attack them. The cellular system is composed of many classes of T-lymphocytes (white blood cells that detect foreign invaders called antigens). The humoral system is made up of B cells, which are the only cells in the body that make antibodies. In SCID, neither the cellular nor the humoral part of the immune system is working properly.

Causes and symptoms

SCID is an inherited disorder. There are two ways in which a developing fetus' immune system can fail to develop normally. In the first type of genetic problem, both B and T cells are defective. In the second type, only the T cells are abnormal, but their defect affects the functioning of the B cells.

For the first few months of life, a child with SCID is protected by antibodies in the mother's blood. As early as three months of age, however, the SCID child begins to suffer from mouth infections (thrush), chronic diarrhea, otitis media and pulmonary infections, including pneumocystis pneumonia. The child loses weight, becomes very weak, and eventually dies from an opportunistic infection.

Diagnosis

SCID is diagnosed by the typing of T and B cells in the child's blood. B cells can be detected by immunofluorescence tests for surface markers (unique proteins)on the cells. T cells can be identified in tissue sections (samples) using enzyme-labeled antibodies.

Treatment

Patients with SCID can be treated with antibiotics and immune serum to protect them from infections, but these treatments cannot cure the disorder. Bone marrow transplants are currently regarded as one of the few effective standard treatments for SCID.

Investigational treatments

In 1990, the Food and Drug Administration (FDA) approved PEG-ADA, an orphan drug (not available in US but available elsewhere), for the treatment of SCID. PEG-ADA, which is also called pegademase bovine, works by replacing the ADA deficiency in children with this form of SCID. Children who receive weekly injections of PEG-ADA appear to have normal immune functions restored. Another treatment that is still in the experimental stage is gene therapy. In gene therapy, the children receive periodic infusions of their own T cells corrected with a gene for ADA that has been implanted in an activated virus.

Prognosis

Currently, there is no cure for SCID. Most untreated patients die before age two.

Prevention

Genetic counseling is recommended for parents of a child with SCID.

Resources

ORGANIZATIONS

Immune Deficiency Foundation. 25 W. Chesapeake Ave., Suite 206, Towson, MD 21204. (800) 296-4433. http://www.primaryimmune.org.

National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812-8923. (800) 999-6673. http://www.rarediseases.org.

KEY TERMS

Adenosine deaminase (ADA) An enzyme that is lacking in a specific type of SCID. Children with an ADA deficiency have low levels of both B and T cells.

Antigens A substance that usually causes the formation of an antibody. A foreign invaders in the body.

Autosomal recessive inheritance A pattern of inheritance of a recessive gene where, among other things, both parents may not show symptoms.

B cell A type of lymphocyte or white blood cell that is derived from precursor cells in the bone marrow.

Congenital Present at the time of birth. Most forms of SCID are hereditary as well as congenital.

Gene therapy An experimental treatment for SCID that consists of implanting a gene for ADA into an activated virus and merging it with some of the patient's own T cells. The corrected T cells are infused back into the patient every few months.

Humoral Pertaining to or derived from a body fluid. The humoral part of the immune system includes antibodies and immunoglobulins in blood serum.

Lymphocyte A type of white blood cell that is important in the formation of antibodies.

Orphan drug A drug that is known to be useful in treatment but lacks sufficient funding for further research and development.

PEG-ADA An orphan drug that is useful in treating SCID related to ADA deficiency.

T cells Lymphocytes that originate in the thymus gland. T cells regulate the immune system's response to infections. The thymus gland is small or underdeveloped in children with SCID.

Thrush A disease of the mouth caused by a yeast, Candida albicans.

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Frey, Rebecca. "Severe Combined Immunodeficiency." Gale Encyclopedia of Medicine, 3rd ed.. 2006. Encyclopedia.com. 24 Jun. 2016 <http://www.encyclopedia.com>.

Frey, Rebecca. "Severe Combined Immunodeficiency." Gale Encyclopedia of Medicine, 3rd ed.. 2006. Encyclopedia.com. (June 24, 2016). http://www.encyclopedia.com/doc/1G2-3451601472.html

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Severe Combined Immunodeficiency (SCID)

Severe combined immunodeficiency (SCID)

Severe combined immunodeficiency (SCID) is a rare genetic disease that is actually a group of inherited disorders characterized by a lack of immune response, usually occurring in infants less than six months old. SCID is the result of a combination of defects of both T-lymphocytes and B-lymphocytes. Lymphocytes are white blood cells that are made in bone marrow, and many move to the thymus gland where they become specialized immune T and B cells . In healthy individuals, T cells attack antigens while B cells make plasma cells that produce antibodies (immunoglobulins ). However, this immune response in SCID patients is absent making them very susceptible to invading diseases, and thus children with untreated SCID rarely live to the age of two years.

SCID is characterized by three main features. The helper T-lymphocytes are functioning poorly or are absent, the thymus gland may be small and functioning poorly or is absent, and the stem cells in bone marrow, from which mature T- and B-lymphocytes arise, are absent or defective in their function. In all of these situations, little or no antibodies are produced. If, for example, T-lymphocytes are never fully developed, then the immune system can never function normally. Moreover, the results of these defects include the following: impairment of normal functioning T- and B-lymphocytes, negative effects on the maturation process for T-helper and T-suppressor cells, and elimination and damage of the original source of the lymphocytes.

The immune disorders characterized in SCID arise because of the inheritance of abnormal genes from one or both parents. The most common form of SCID is linked to the X chromosome inherited from the mother; this makes SCID more common among males. The second most common defect is caused by the inheritance of both parents' abnormally inactive genes governing the production of a particular enzyme that is needed for the development of immunity , called adenosine deaminase (ADA). Although many defective genes for other forms of SCID have been identified in the last few years, scientists do not fully understand all of the forms of the disease.

There are many specific clinical signs that are associated with SCID. After birth, an infant with SCID is initially protected by the temporarily active maternal immune cells; however, as the child ages, his or her immune system fails to take over as the maternal cells become inactive. Pulmonary problems such as pneumonia , non-productive coughs, inflammation around the bronchial tubes, and low alveolar oxygen levels can affect the diseased infant repetitively. Chronic diarrhea is not uncommon, and can lead to severe weight loss, malnutrition, and other gastrointestinal problem. Infants with the disease have an unusual number of bacterial, fungal, viral, or protozoal infections that are much more resistant to treatment than in healthy children. Mouth thrush and yeast infections, both fungal, appear in SCID patients and are very resistant to treatment. Additionally, chronic bacterial and fungal skin infections and several abnormalities of the blood cells can persist.

Severe combined immunodeficiency is a disease that can be successfully treated if it is identified early. The most effective treatment has been hematopoietic stem cell transplants that are best done with the bone marrow of a sister or brother; however, the parent's marrow is acceptable if the infant is less than three months old. Early treatment can also help to avoid pre-transplant chemotherapy often necessary to prevent rejection of the marrow in older children. This is especially advantageous because chemotherapy can leave the patient even more susceptible to invading bodies. When successful, treatment for SCID corrects the patient's immune system defect, and as of 2002 success rates have been shown to be nearly 80% for the bone marrow transplant.

Gene therapy is the subject of ongoing research, and shows promise as a treatment for SCID. Researchers remove T cells of SCID patients and expose those cells to the ADA gene for ten days, and then return the cells intravenously. Although it was successful in one case, this treatment of SCID is still very much in the experimental stage. Nevertheless, these and other treatments hold potential for the development of a cure for SCID.

See also Immune system; Immunochemistry; Immunodeficiency disease syndromes; Immunodeficiency diseases; Immunogenetics; Immunoglobulins and immunoglobulin deficiency syndromes; Immunological analysis techniques; Immunology

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"Severe Combined Immunodeficiency (SCID)." World of Microbiology and Immunology. 2003. Retrieved June 24, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3409800511.html

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