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Primary Immune Deficiency Diseases

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Severe Combined Immunodeficiency (SCID)

SCID is a group of rare disorders caused by mutations in different genes involved in the development and function of infection-fighting T and B cells. Infants with SCID appear healthy at birth, but they are highly susceptible to severe infections. The condition is fatal, usually within the first year or two of life, unless infants receive immune-restoring treatments, such as transplants of blood-forming stem cells, gene therapy, or enzyme therapy. More than 80 percent of SCID infants do not have a family history of the condition. However, development of a newborn screening test has made it possible to detect SCID before symptoms appear, helping ensure that affected infants receive life-saving treatments.

Causes

SCID is caused by defects in different genes involved in the development and function of infection-fighting immune cells. More than a dozen genes have been implicated in SCID, but gene defects are unknown in approximately 15 percent of newborn-screened SCID infants, according to an NIH-funded study.

Most often, SCID is inherited in an autosomal recessive pattern, in which both copies of a particular gene—one inherited from the mother and one from the father—contain defects. The best-known form of autosomal recessive SCID is caused by adenosine deaminase (ADA) deficiency, in which infants lack the ADA enzyme necessary for T-cell survival.

X-linked SCID, which is caused by mutations in a gene on the X chromosome, primarily affects male infants. Boys with this type of SCID have lymphocytes that cannot grow, develop, or communicate with B cells. As a consequence, they have low numbers of T cells and natural killer cells, and their B cells do not function.

Newborn Screening Test

The SCID newborn screening test, originally developed at NIH, measures T cell receptor excision circles (TRECs), a byproduct of T-cell development. Because SCID infants have few or no T cells, the absence of TRECs may indicate SCID. To confirm a SCID diagnosis, a doctor will evaluate the numbers and types of T and B cells present and their ability to function.

SCID was added in 2010 to the U.S. Department of Health and Human Services’ Recommended Uniform Screening Panel for newborns. Early diagnosis of SCID through newborn screening leads to prompt treatment and high survival rates, according to a study partly funded by NIAID.

Read more: Test Reliably Detects Immune Deficiency in Newborns

Signs and Symptoms

Typically, symptoms of SCID occur in infancy and include serious or life-threatening infections, especially viral infections, which result in pneumonia and chronic diarrhea. Candida (yeast) infections of the mouth and diaper area and pneumonia caused by the fungus Pneumocystis jirovecii also are common in affected infants.

Treatment

Hematopoetic (blood-forming) stem cell transplantation is the standard treatment for SCID. Transplants can fully restore the T-cell and, less consistently, the B-cell deficiencies of SCID.

Results from an NIAID-funded study indicate that early transplantation is critical to achieving good outcomes for SCID infants. Researchers analyzed data from 240 SCID infants at 25 transplant centers across North America. They found that infants who received transplants before the age of 3.5 months were most likely to survive, regardless of the type of stem cell donor used. Babies of any age who did not have infection at the time of transplant also had high survival rates.

Read more: Early Treatment Benefits Infants With Severe Combined Immunodeficiency

Studies have shown that gene therapy can be an effective treatment for some types of SCID, such as X-linked SCID (SCID-X1). In gene therapy, doctors remove stem cells from the patient’s bone marrow, insert a corrected gene using a carrier known as a vector, and return the corrected cells to the patient. Initial efforts to treat SCID-X1 with gene therapy successfully restored children’s T cell function. However, approximately one-quarter of the children developed leukemia two to five years after treatment. Scientists suspect that the vectors used in these studies activated genes that control cell growth, contributing to leukemia. In 2014, NIAID-funded researchers reported development of a modified vector that appears effective and safe.

Read more: Gene Therapy Shows Promise for Severe Combined Immunodeficiency

Children who have SCID with ADA deficiency have been treated somewhat successfully with enzyme replacement therapy called PEG-ADA.

Last Updated October 09, 2014

Last Reviewed October 09, 2014