Severe combined immunodeficiency (SCID) is a primary immune deficiency caused by many different genetic defects that affect the immune system. In SCID, the term “severe” is used because the extent of the defect can lead to death from infections in infancy or early childhood that a normal immune system would manage more effectively. The term “combined” is due to the presence of defects in both cell mediated (T lymphocytes) immunity and humoral- antibody production (defects in B- lymphocytes). Lymphocytes are white blood cells that circulate in the blood stream as well as migrate to areas of the body where germs enter such as the lining of the mouth, nares, throat, intestinal tract and skin. In addition, lymphocytes collect in small, bean-shaped structures called lymph nodes, as well as in the spleen, bone marrow and a special organ in the chest called the thymus.
Lymphocytes have different subtypes, the most common of which, are called T-lymphocytes (T-cells) and B-lymphocytes (B-cells). T-cells have many functions including recognizing foreign intruders (germs), killing bacteria and germs where they enter the body, sending information to other parts of the immune system to help coordinate defense against germs and giving B-cells information to make antibodies against germs that enter the body. B-cells receive information from the immune system and produce specific sticky proteins called antibodies, which help in the defense against bacteria and viruses. Babies born with a genetic defect that leads to SCID do not deal well with infections from bacteria, viruses or fungi. These babies do not respond to vaccines and produce no protective immune response from the vaccines and have defects in both B-cell and T-cell function.
Types of SCID
Since SCID was first reported in 1950, studies of the pattern of disease inheritance indicated there was more than one cause for this condition. In many families, the disease was inherited through a recessive gene linked to the X chromosome (X-linked recessive) while in others it was passed on through an autosomal, or non-sex–linked, recessive gene (autosomal recessive).1,2
It is now known that SCID can be caused by mutations in at least 15 different genes, and it is likely there are other causes yet to be discovered.1
About ADA and ADA-SCID
Adenosine deaminase (ADA) is an important enzyme in blood cells. A genetic defect results from mutations (defects) in the ADA gene that leads to a severe deficiency of the enzyme. This enzyme is found throughout the body but is most active in lymphocytes. When functioning properly, the adenosine deaminase enzyme eliminates a molecule that is toxic to lymphocytes. This molecule, deoxyadenosine, is produced when DNA is broken down. Adenosine deaminase converts deoxyadenosine to deoxyinosine, a molecule that does not harm lymphocytes. However, mutations in the ADA gene reduce or eliminate the protective activity of adenosine deaminase, allowing the buildup of deoxyadenosine to toxic levels. These toxic levels cause T-cells and B-cells to accumulate biologic chemicals of normal cell function that would be processed by ADA. The buildup of these biologic products in excess of normal causes the T-cells and B-cells to die and leaves the infants with no significant immune defense.1,3
As a result, individuals with ADA-SCID lack immune protection from bacteria, viruses, and fungi, putting them at increased risk of severe and recurring infections caused by opportunistic organisms that ordinarily do not lead to illness in people with normally functioning immune systems. The most common symptoms of ADA-SCID are pneumonia, chronic diarrhea, and skin rashes. Additionally, children with ADA-SCID grow more slowly than healthy children, and some have developmental delays.1-4
The vast majority of patients with ADA deficiency (about 85% to 95%) present with ADA-SCID, which is estimated to occur in approximately one in 200,000 to one in 1,000,000 newborns around the world. ADA-SCID is typically diagnosed within the first six months of life; left untreated, babies with ADA-SCID usually die before they reach age two unless they are diagnosed early and effective treatment is started.3-4
Routine Screening for SCID
Not all states require routine screening for SCID (including ADA-SCID) in newborns. The test is routinely offered, but not yet required in some states, and in others the test is required, but not yet implemented.5 The Advisory Committee on Heritable Disorders in Newborns and Children has recommended routine newborn screening for SCID and will be determining whether national screening should be mandatory.6-7 Use of the newer technology known as TREC (T-cell Receptor Excision Circles) can be done at birth to identify babies with SCID and intervene with supportive care. Babies found to be positive can have assays (enzyme tests) for ADA to identify babies with ADA deficiency before symptoms or illness develop. 7