Severe combined immunodeficiency
SCID, or severe combined immunodeficiency, is a group of rare, life-threatening diseases present at birth that impair the immune system. Without a healthy immune system the body cannot fight infections and individuals can easily become seriously ill from common infections.
SCID is one type of Primary Immunodeficiency Diseases (PID) and is considered the most severe. There are approximately 70 forms of PID. Primary immunodeficiency diseases are where a person is missing a component of the immune system—either an organ or cells of the immune sytem. Some deficiencies are deadly, while others are mild.
SCID is also known as the "boy in the bubble" syndrome, because living in a normal enviroment can be fatal. SCID initially was called Swiss agammaglobulinemia because it was first described in Switzerland in 1961. Any exposure to germs can pose a risk for infection, including bacterial, viral, and fungal. In the first few months of life, children with SCID become very ill with infections such as pneumonia (infection of the lungs which prevents oxygen from reaching the blood, making breathing difficult), meningitis (infection of the covering of the brain and spinal cord), sepsis (infection in the bloodstream) and chickenpox, and can die within the first year of life, since their immune system is unable to fight off these infections.
Children with SCID do not respond to medications like other children because their immune system does not function properly. They may also not have a developed thymus gland. Medication usually stimulates a person's immune system to fight infection, but in the case of SCID, the immune system is unable to respond. The immune system is a complex network of cells and organs that protect the body from infection. The thymus and lymphatic system (lymph nodes and lymphatic vessels) house and tranport two very important cells that fight infection: the B and T cells. The bone marrow (center of bones) produces cells that become blood cells as well as cells for the immune system. One type of cell, called lymphocytes or white blood cells, mature in the bone marrow to form "B" cells, while others mature in the thymus to become "T" cells. B and T cells are the two major groups of lymphocytes that recognize and attack infections. Children with SCID have either abnormal or absent B and T cells.
Other infections can be seen in children with SCID including skin infections, yeast infections in the mouth and diaper area, diarrhea, and infection of the liver. Children with SCID fail to gain weight and grow normally. Treatment for SCID is available, however, many children with SCID are not diagnosed in time and die before their first birthday.
A diagnosis of SCID, besides being painful, frightening, and frustrating, needs to be made quickly since common infections can prove fatal. In addition, permanent damage can result in the ears, lungs, and other organs.
SCID is a group of inherited disorders with about half inherited by a gene on the X chromosome called IL2RG, 15% inherited by an autosomal recessive gene called ADA, and the remaining 35% caused by either an unknown autosomal recessive gene or are the result of a new mutation.
Genetic information is carried in tiny packages called chromosomes. Each chromosome contains thousands of genes and each gene contains the information for a specific trait. All human cells (except egg and sperm cells)
The last pair of human chromosomes, either two X's (female) or one X and one Y (male)—determines gender. X-linked means the gene causing the disease or trait is located on the X chromosome. The term "recessive" usually infers that two copies of a gene—one on each of the chromosome pair—are necessary to cause a disease or express a particular trait. X-linked recessive diseases are most often seen in males, however, because they only have one copy of the X chromosome. Therefore, if a male inherits a particular gene on the X chromosome, he expresses the gene, even though he only has a single copy. Females, on the other hand, have two X chromosomes, and therefore can carry a gene on one of their X chromosomes yet not express any symptoms. (Their second X chromosome copy works normally). A mother usually carries the gene for SCID unknowingly, and has a 50/50 chance with each pregnancy to transmit the gene. If the child is a male, he will have SCID; if the child is female, she will be a carrier for SCID like the mother.
New mutations—alterations in the DNA of the gene—can cause disease. In these cases, neither parent has the disease-causing mutation. This may occur because the mutation in the gene happened for the first time only in the egg or sperm for that particular pregnancy. New mutations are thought to happen by chance and are therefore referred to as "sporadic", meaning, by chance.
It is estimated that about 400 children a year are born with some type of primary immunodeficiency disease. Approximately one in 100,000 children are born with SCID each year, regardless of the part of the world the child is from, or the ethnic background of the parents. This disease can affect both males and females depending on its mode of inheritance.
Signs and symptoms
Babies with SCID fail to thrive, are frail, and do not grow well. They have numerous, serious, life-threatening infections that usually begin in the first few months of life. Because they do not respond to medications like other children, they may be on antibiotics for 1-2 months with no improvement before a physician considers a diagnosis of SCID. The types of infections typically include chronic (developing slowly and persisting for a long period of time) skin infections, yeast infections in the mouth and diaper area, diarrhea, infection of the liver, pneumonia, meningitis, and sepsis. They can also have serious sinus and ear infections, as well as a swollen abdomen. Sometimes deep abscesses occur, which are
About half of children who see a doctor for frequent infections are normal; another 30% may have allergies, 10% have some other type of serious disorder, and 10% have a primary or secondary immunodeficiency. A diagnosis of SCID is usually made based on a complete medical history and physical examination, in addition to multiple blood tests and chest x rays. The gene in X-linked recessive SCID is called the interleukin receptor gamma chain gene or IL2RG. The autosomal recessive forms of SCID are caused by a variety of different genes; one of the more common is called the adenosine deaminase gene or ADA. Since newborns do not routinely have a test to count white blood cells, SCID is not usually suspected and then diagnosed until the child develops their first infection. A pattern of recurrent infections suggests an immunodeficiency.
Once a couple has had a child with SCID, and they have had the genetic cause identified by DNA studies (performed from a small blood sample), prenatal testing for future pregnancies may be considered on a research basis for some types of SCID. (Note that prenatal testing may not be possible if a mutation cannot be identified). Prenatal diagnosis is available via either CVS (chorionic villus sampling) or amniocentesis. CVS is a biopsy of the placenta performed in the first trimester or the first 12 weeks of pregnancy under ultrasound guidance. Ultrasound is the use of sound waves to visualize the locations of the developing baby and the placenta. The genetic makeup of the placenta is identical to the fetus (developing baby) and therefore the prescence or absence of one of the SCID genes can be determined from this tissue. Amniocentesis is a procedure performed under ultrasound guidance where a long thin needle is inserted into the mother's abdomen, into the uterus, to withdraw a couple of tablespoons of amniotic fluid (fluid surrounding the developing baby) to study. The SCID gene can be studied using cells from the amniotic fluid. Other genetic tests, such as a chromosome analysis, may also be performed on either a CVS or amniocentesis. A small risk of miscarriage is associated with CVS and amniocentesis.
Treatment and management
The best treatment for SCID is a bone marrow transplant (BMT). A bone marrow transplant involves taking cells that are normally present in bone marrow (the center of bones that produce and store blood cells), and giving them back to the child with SCID or to another person. The goal of BMT is to infuse healthy bone marrow cells into a person after their own unhealthy bone marrow has been eliminated. BMT helps to strengthen a child with SCID's immune system.
Other treatment for SCID includes treating each infection promptly and accurately. Injections are also available to help boost a child's immune system.
In the year 2000, gene therapy was first reported to be successful in two French patients with SCID. The idea behind gene therapy is to replace an abnormal gene with a normal copy. In SCID, bone marrow is removed to isolate the patients' stem cells. Stem cells are special cells in the bone marrow that produce lymphocytes. In a laboratory, the normal gene is added to the abnormal stem cells. The genetically altered stem cells now have the normal gene and are transplanted back into the patient. Once the functioning stem cells with the normal gene enter the bone marrow, they reproduce quickly and replace stem cells that have the abnormal gene. So, ultimately, the patient with SCID produces B and T cells normally and can fight off infections without antibiotics or other treatment. The long-term effects of gene therapy are unknown, since the children treated are still very young.
When SCID is diagnosed early, successful bone marrow transplantation usually corrects the problem and the child lives a normal life. This means children can go to school, mix with playmates, and take part in sports. However, the quality of life for individuals with severe cases of SCID can be greatly impaired if they do not receive a bone marrow transplant. Children with SCID may not live long if they do not receive the proper treatment or if their disease goes undiagnosed.
Buckley, Rebecca H. "Gene Therapy for Human SCID: Dreams Become Reality." Nature Medicine 6 (June 2000): 623.
Stephenson, Joan. "Gene Therapy Trials Show Efficacy." Journal of the American Medical Association 283 (February 2, 2000): 589.
Immune Deficiency Foundation. 40 W. Chesapeake Ave., Suite 308, Towson, MD 21204. (800) 296-4433. Fax: (410) 321-9165. <http://www.primaryimmune.org>.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
International Patient Organization for Patients with Primary Immunodeficiencies. <www.ipopi.org>.
Pediatric Primary ImmuneDeficiency. <www.pedpid.com>.
Severed Combined ImmuneDeficiency Homepage. <www.scid.net>.
Catherine L. Tesla, MS, CGC