General Condition Information
- Severe combined immune deficiency
- Severe combined immunodeficiency
- Severe combined immunodeficiency disease
- X-linked severe combined immunodeficiency, JAK3-deficient severe combined immunodeficiency, ZAP70-related severe combined immunodeficiency
What is Severe combined immunodeficiencies
Severe combined immunodeficiencies (SCID) are a group of genetic conditions where a baby is born with a nonworking or poorly working immune system.
We need the immune system to fight infections. The immune system uses white blood cells called lymphocytes to fight against germs that invade the body. Lymphocytes include T cells, B cells, and natural killer (NK) cells.
In SCID, these T cells, B cells, or NK cells are absent or do not work correctly. There are several types of SCID. The type of SCID your baby has depends on which part of the immune system is problematic. The most common types of SCID are X-linked SCID and adenosine deaminase (ADA) deficiency.
X-linked SCID occurs mostly in boys and is also called “bubble-boy” disease. That is because a boy with the condition, David Vetter, lived in a plastic enclosure for 12 years before the availability of current treatments. In this condition, a protein needed to make normal T cells and NK cells is absent or nonworking. B cells are present, but they cannot work as well without help from the T cells. This type of SCID is in a category called T-B+NK- SCID, named after the types of lymphocytes affected.
ADA deficiency occurs when the enzyme adenosine deaminase is not made correctly. This enzyme helps remove toxic substances in cells that can destroy lymphocytes. Without working adenosine deaminase enzymes, these toxic products build up and kill all lymphocytes – T, B, and NK cells. This type of SCID is placed in the category T-B-NK- SCID.
There are also many other rare causes of SCID. In all causes of SCID, a change in the baby’s genes leads to similar problems with their immune system.
The most severe type of SCID is referred to as classic or typical SCID.
Another form of the condition is called leaky SCID. Unlike typical SCID, babies with leaky SCID may have small numbers of T cells, or only have T cells that do not work normally. This condition is also called Omenn syndrome.
If the immune system is absent or weak, your baby’s body has trouble fighting infections. They can get sick from germs that do not infect people with normal working immune systems, leading to the signs and symptoms of the condition. Without treatment and special protection from germs, SCID can lead to life-threatening illness or death.
Newborn Screening and Follow-Up
Newborn screening for SCID is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a machine measures how many small pieces of DNA, called T cell receptor excision circles, (TRECs) are in your baby’s blood. The body produces TRECs when it is developing the T cells of the immune system. Babies without an immune system, or one that does not work as it should, will have little or no TRECs. These babies might have SCID.
If your baby’s blood spot screening result for SCID is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has SCID. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood tests
- Genetic tests using a blood sample or other sample (collected from the mouth or skin, if needed)
You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems in the first few months after birth if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition do occur. Screening samples collected from babies who were born early (premature) or who are very sick (in the newborn intensive care unit, or NICU) for other reasons can have false-positive results. This screening can also pick up other conditions that affect the immune system.
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
Signs of SCID usually appear in the first few months after birth. SCID is often categorized into two types based on what signs and symptoms appear and how severe they are.
Signs of classic or typical SCID may include the following:
- High number of infections or infections caused by germs that do not affect healthy babies
- Infections that do not get better with antibiotic treatment
- Skin rashes
- Creamy white dots in the mouth or throat that do not get better (thrush)
- Poor weight gain or growth (failure to thrive)
Babies with leaky SCID have signs and symptoms similar to typical SCID.
Signs of leaky SCID may include the following:
There are many different genetic causes of SCID. In nearly all cases, SCID is caused when one of several genes, which gives the body instructions for making parts of the immune system does not work.
X-linked SCID is caused by changes in the IL2RG gene. ADA deficiency is caused by changes in the ADA gene. There are several other genes associated with SCID that can be found by newborn screening. These types include those caused by changes in the RAG1, RAG2, DCLRE1C, NHEJ1, CD247, CD3E, CD3D, AK2, IL7RA, or PTPRC genes, among others.
In SCID, the immune system’s white blood cells, including T cells, B cells, or NK cells, are not made or do not work properly. Without these cells, especially T cells, the body cannot fight infections.
SCID is a genetic condition that is usually inherited. Babies inherit it from their biological (birth) parents. Rarely, a baby may spontaneously develop a genetic change associated with SCID, which is not inherited from either parent. To learn more about genetic conditions, visit MedlinePlus Genetics.
- The most common type of SCID, X-linked SCID, is inherited in an X-linked recessive pattern, which means babies inherit this condition on their X chromosome.
- Girl babies have two X chromosomes, so only girls with two nonworking genes have SCID. Girls with one nonworking gene are carriers.
- Boy babies only have one X chromosome, so boys with only one nonworking gene have SCID. This condition is more common in boys.
- Some types of SCID, including ADA deficiency, are autosomal recessive conditions. Babies inherit the condition when each parent passes down a nonworking gene to their baby. Only babies with two nonworking genes—one from the mom and one from the dad—have this condition.
- People with one working copy and one nonworking copy of the gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the gene, they have a 1 in 4 chance of having a child with SCID.
- Carriers for SCID often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with SCID.
- Parents who already have a child with SCID still have a 1 in 4 chance of having another child with SCID. This 1 in 4 chance stays the same for all future children.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
Treatment options for this condition are listed below. It is important to talk to your health care provider about which treatment(s) are best for your baby.
The goal of treatment is to prevent the health problems caused by this condition. Treatments may include the following:
- Isolation (avoiding infections/germs)
- Antibody treatment (also called immunoglobulin replacement therapy)
- Antimicrobial therapy (antibiotics, antifungals, antiviral medications)
- Bone marrow transplant to help replace and grow an immune system
- Thymus transplant (for specific forms of SCID)
- Gene therapy (for certain forms of SCID, e.g., X-linked SCID and ADA-SCID).
Children who receive early and ongoing treatment for SCID are less likely to have life-threatening infections and illnesses and have better long-term survival. Children who receive bone marrow, thymus transplants, or gene therapy can lead healthier lives.