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: http://www.primaryimmune.org.

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

WEB SITES

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

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