Severe combined immunodeficiency

Severe combined immunodeficiencies (SCID) are inherited immune system disorders characterized by abnormalities with responses of both T cells and B cells (specific types of white blood cells needed for immune system function). Common signs and symptoms include an increased susceptibility to infections including ear infections; pneumonia or bronchitis; oral thrush; and diarrhea. Due to recurrent infections, children with SCID do not grow and gain weight as expected (failure to thrive). SCID may be caused by mutations in any of several genes and can be inherited in an X-linked recessive (most commonly) or autosomal recessive manner. The most common type of SCID is called X-linked severe combined immunodeficiency (XSCID). Another form of SCID is caused by a deficiency of the enzyme adenosine deaminase (ADA).^[1] Infections are treated with specific antibiotic, antifungal, and antiviral agents and administration of intravenous (IV) immunoglobulin.^[2] The most effective treatment is transplantation of blood-forming stem cells from the bone marrow of a healthy person.^[1]

A diagnosis of SCID may be suspected if a baby shows any of the following persistent symptoms within the first year of life:^[3]

• Eight or more ear infections
• Two or more cases of pneumonia
• Infections that do not resolve with antibiotic treatment for two or more months
• Failure to gain weight or grow normally
• Infections that require intravenous (IV) antibiotic treatment
• Deep-seated infections, such as pneumonia that affects an entire lung or an abscess in the liver
• Persistent thrush in the mouth or throat
• A family history of immune deficiency or infant deaths due to infections

A diagnosis can be confirmed by blood tests. Blood tests show significantly lower-than-normal levels of T cells and antibodies.^[3]  

Since there are other conditions that can result in lower-than-normal numbers of the different types of lymphocytes, the most important tests are those of T-cell function by placing blood lymphocytes in culture tubes, and treating them with various stimulants. Normal T-lymphocytes react to these stimulants by undergoing cell division. In contrast, lymphocytes from patients with SCID usually do not react to these stimuli.

Immunoglobulin levels are usually very low in SCID. Most commonly (but not always), all immunoglobulin classes are depressed (IgG, IgA, IgM and IgE).

The diagnosis of SCID can also be made before the baby is born if there has been another infant in the family with the disorder and if the gene defect has been identified. If genetic analysis had been completed on the infant in the family with SCID, a diagnosis can be determined during subsequent pregnancies. This can be done by molecular testing of cells from a chorionic villous sampling (CVS) or from an amniocentesis, where a small amount of amniotic fluid (which contains fetal cells) is removed.

Early diagnosis, before the infant has had a chance to develop any infections, is very valuable since bone marrow transplants given in the first three months of life have a 94% success rate. In fact, screening newborns to detect SCID soon after birth has been made possible because of recent scientific advances. Approximately half of the babies born in the U.S. are now being screened for SCID.