SCID (Severe Combined Immunodeficiency)
Severe combined immunodeficiency (SCID) is the name for a group of inherited immune system disorders. Immune deficiency disorders are the most severe of the inherited immune system disorders. Babies are born with these disorders, which can become life-threatening within the first year of life. SCID is rare. About 1 in 500,000 babies are born with SCID.
Causes of SCID
Inherited immune disorders are also called primary immune deficiency disorders. They are caused by a mutation (mistake) in a gene that affects the immune system. Genes carry an inherited code of instructions that tells the body how to make every cell and substance in the body.
Some types of SCID are caused by a gene mutation on the X chromosome, which comes from the mother. Disorders inherited on the X chromosome appear only in males. A female with the mutated gene will not have the disease but will be a carrier. This means she may pass the mutated gene on to her children.
Other types of immunodeficiencies appear when a gene mutation is inherited from both parents (the child has two copies of the same gene mutation). These immune deficiency disorders appear in both males and females.
In most cases, no one knows what causes the mutation to appear the first time. Once a mutation appears, it can be passed from parent to child through many generations.
SCID and the Immune System
The immune system is made up of organs and cells that work together to protect the body from infection and disease. The immune system uses white blood cells to fight infections. The white blood cells mark and attack cells that they do not recognize as belonging in the body.
There are several types of white blood cells, each with its own role. In children with SCID, the immune system does not work well because of problems with certain types of white blood cells known as lymphocytes. There are three types of lymphocytes:
- B cells make antibodies. Antibodies attach to foreign cells and mark them to be attacked.
- T cells direct B cells to make antibodies against foreign cells. T cells also direct the rest of the immune system when to attack or stop attacking foreign cells. They also help in the attack.
- Natural killer cells (NK cells) destroy infected cells and cancer cells.
Symptoms and Diagnosis of SCID
Children with SCID are at risk for life-threatening infections. From their first months of life, they have infections that may be frequent, severe, long-lasting or hard to treat. Infections may occur in the lungs (pneumonia), around the brain and spinal cord (meningitis) or in the blood stream. Many babies also get diarrhea that does not go away. Babies with immune deficiency do not gain weight or grow at a healthy rate (failure to thrive). A baby diagnosed with SCID needs immediate treatment. Without effective treatment, most children with SCID die of infection with failure to thrive within the first year of life.
Diagnosis
If a baby shows signs of a possible immune disorder, a doctor can do a blood test to count the number of lymphocytes (the white blood cells affected in SCID) and test their function. Babies with SCID will have very low numbers.
Families affected by SCID may want to talk with a genetic counselor about family planning and the chances of having children with the disorder. Early diagnosis can enable early treatment and improve a child's chances of a good outcome.
Types of SCID
There are several types of SCID. Two of the more common are:
- Classical X-linked immunodeficiencies -- Almost half of patients with SCID have classical X-linked SCID (sometimes called "boy in the bubble" disease). It is inherited on the X chromosome and appears only in boys.
- ADA deficiency SCID -- About 15% of patients with SCID have adenosine deaminase (ADA) deficiency. These patients have low levels of the enzyme ADA. Lack of ADA leads to low numbers of T cells and B cells. This type of SCID can appear in either girls or boys.
Preventing Infections
For children with SCID, the first concern is to prevent infections. Children with immune deficiency disorder need to be protected from germs. This includes keeping them away from crowds and sick people. They are often treated with antibiotics to prevent infection.
They will also be given intravenous immune globulin (IVIG). Immune globulin is also called immunoglobulin or gammaglobulin. It contains antibodies that would normally be made by healthy B cells to help the body fight infection. Immune globulin is usually infused into a vein. Patients with SCID will probably get one IVIG infusion a month. Each infusion may take from one to five hours. Treatments may be given in a doctor's office, hospital outpatient unit or at home. Many people have no side effects from IVIG infusion, but some people may have side effects such as chills, headaches, fever, nausea and chest tightness. These can usually be controlled with medicine or adjustments to the rate of infusion.
Enzyme Therapy for ADA Deficiency SCID
The standard treatment for ADA immune deficiency disease is treatment with a form of the ADA enzyme called PEG-ADA. Treatment with PEG-ADA is effective in about 90% of children. However, some also still need IVIG treatments.
Gene Therapy
A treatment option being studied in clinical trials is gene therapy. Gene therapy has been a successful treatment for some patients with ADA deficiency SCID. At first, gene therapy also appeared to be a promising treatment for X-linked immunodeficiencies, but some children treated with gene therapy developed leukemia. New trials of gene therapy are in progress.