What is severe combined immunodeficiency?
Severe combined immunodeficiency (SCID) is very rare, genetic disorder, affecting between 50 and 100 children born in the U.S. every year. SCID is often called “bubble boy disease,” made known by the 1976 movie “The Boy in the Plastic Bubble.”
Essentially, children with SCID lack the ability to produce an immune system. The human immune system constantly patrols, protects and defends the body from all types of “enemies,” including:
The immune system first takes root in a developing fetus’s bone marrow. That’s where some stem cells eventually mature into the two cell types that play the biggest role in warding off infection: T cells (white blood cells that identify and attack perceived “invaders”) and B cells (white blood cells that produce antibodies against infection).
A child with SCID:
- can't produce T cells
- doesn't have working B cells (because there are no T cells for them to work with)
- has virtually no immune system
Without a functioning immune system, a child with SCID has no way of warding off infections. He or she will be at constant risk for:
Severe Combined Immunodeficiency | Symptoms & Causes
What are the symptoms of severe combined immunodeficiency?
Severe combined immunodeficiency (SCID) can be difficult to detect because babies with the disorder may not show any signs of illness until they develop a telltale infection. In most cases, infections are the first indication that a child may have SCID, though in some children the first sign is a failure to thrive.
What causes SCID?
There are more than 15 recognized kinds of SCID, but the most common type, known as SCID-X1 (for “X-linked severe combined immunodeficiency”), involves a defect in a gene on the X chromosome. Because girls have two X chromosomes while boys have only one, SCID-X1 affects only male children. However, girls can be “carriers” and can pass the disorder on to their own sons later in life.
Different genetic defects cause each form of SCID. But all types of SCID are genetic — meaning they are caused by an error or mutation in the child’s genes.
Even though SCID is a genetic condition, having one child with SCID does not necessarily mean other family members, including siblings, are going to develop the disease. However, it is a good idea to ask your doctor about genetic counseling for you and your other children.
Severe Combined Immunodeficiency | Diagnosis & Treatments
How is severe combined immunodeficiency diagnosed?
A diagnosis of severe combined immunodeficiency (SCID) is usually based on a complete medical history and physical examination of your child. In addition, multiple blood tests — including a complete blood cell count — may be ordered to help confirm the diagnosis.
Newborn screening also plays an important role in detecting SCID before symptoms emerge. A growing number of states test for SCID as part of a mandated newborn screening process. Having a screening performed is especially important, because many infants with SCID show no signs until they actually develop an infection.
Screening does have its limitations. A positive result for SCID on a newborn screen is not the same as a conclusive diagnosis, and screening does not catch all children with SCID and SCID variants. However, it is an important means by which children who may have SCID can be detected early.
What are the treatment options for SCID?
Guarding against infection
Nothing is more important to the health of a child with SCID than warding off potential infections. Your child's clinician can advise you about the exact steps you should be taking to help reduce the risk of infection.
Mothers of newborn children with SCID should discuss the pros and cons of breastfeeding with their clinicians, as some infections can be passed through breast milk.
As a rule, children with SCID should not receive the standard childhood vaccinations. Because the B cells of children with SCID do not function properly, their bodies can't produce the normal antibodies that fight off viruses. Since many vaccines are actually live viruses, they pose too high a risk of infection to be safe for a child with a drastically weakened immune system.
Other ways to avoid potential infections include basic precautions such as:
- keep your child away from crowds, dirty places or anyone who is ill or seems to be "coming down with something"
- follow a strict hand washing regimen for your child, your family and any visitors
- use protective face masks at the recommendation of your child's doctor
- give your child antibiotics, antifungal or antiviral medications at the direction of your child's doctor
Because your child's body does not have healthy B cells that produce antibodies against infection, he or she may need regular intravenous (IV, administration through a vein) or subcutaneous infusions (administration under the skin) of the antibody immunoglobin (also known as immune globin, gammaglobin, IVIG or SCIG).
Stem cell/bone marrow transplants
Nearly every child with SCID is treated with a stem cell transplant, also known as a bone marrow transplant. This is the only available treatment option that has a chance of providing a permanent cure. The bone marrow cells or stem cells are administered through an IV, similar to a blood transfusion.
Stem cells are a versatile type of cell found in bone marrow. These cells have a unique and powerful ability: they can develop into several different types of specialized cells.
In the case of a child with SCID, the transplanted stem cells are injected into the bloodstream. They will then become healthy white blood cells that replenish immune functions — essentially building a whole new, functional immune system for the child. If the immune system regains complete function, the child may be permanently cured.
The effectiveness of a stem cell transplant for SCID depends on:
- your child's overall health at the time of the procedure
- the match between your child and donor's bone marrow (If the donated marrow comes from a matched sibling, the procedure has a better than 90 percent success rate.)
- your child's age at the time of the transplant (For optimal success, a baby should have the transplant performed no later than the age of 3 months; some studies have shown that, if stem cell transplants are performed within the first 28 days of a baby's life, the success rate is as high as 95 percent.)
There can be some obstacles to a successful stem cell transplant. For instance, a suitable donor may not be available. In addition, any transplant carries a risk of a phenomenon known as graft-versus-host disease. This means that the donated bone marrow attacks the recipient, which can be a fatal complication.
SCID-X1 gene therapy
Gene therapy is a potential new option for boys with the X-linked form of SCID (SCID-X1), involving mutations in the IL-2RG gene, who don’t have a matched brother or sister to donate their bone marrow. Since 2010 we have helped to lead an international clinical trial of SCID-X1 gene therapy. This approach treats patients’ own blood stem cells, so a bone marrow donor is not needed. SCID-X was the first inherited condition in which gene therapy in blood stem cells was performed successfully.
December 2020 marked a decade since Agustín Cáceres of Argentina was "renacido" — reborn. That’s how his parents describe the day their son received his new gene.
Patients undergoing SCID-X1 gene therapy first have their blood stem cells collected from their blood and treated in a highly specialized laboratory. A self-inactivating virus, specially designed for safety, is used as a carrier to insert a correct version of the faulty IL2RG gene into the patient’s stem cells. Then, the patient receives chemotherapy to make room for the genetically altered cells. Finally, the cells are given back to the patient via an intravenous infusion.
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What is the long-term outlook for children with SCID?
If your child's immune system is restored to good working order, he or she should be able to enjoy a rich, active adult life, including having a family.
It is important to note, some forms of SCID can run in families. For example, SCID-X1 is passed on to boys from mothers who carry the gene mutation on the X chromosome. Genetic counseling is essential for prospective parents with a family history of SCID or any other immune deficiency.
How we care for severe combined immunodeficiency
Boston Children’s Hospital has a long history of caring for children with complex disorders of the immune system. Clinicians in our Division of Allergy and Immunology are international leaders in understanding and treating rare conditions like SCID.
We offer stem cell transplant, also known as a bone marrow transplant, which enables children to develop new white blood cells, replenishing their immune systems. We are also completing a clinical trial of gene therapy for children with the X-linked form of SCID (SCID-X), which accounts for 40-50% of all cases. This international trial, which we helped lead, genetically corrects stem cells from a child’s own bone marrow and returns them to the child.