An Overview of Severe Combined Immunodeficiencies

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Severe combined immunodeficiencies are a group of closely related genetic diseases that severely impair the immune system. They are sometimes called “SCID” (pronounced “skid”). If unrecognized and untreated, SCIDs are potentially fatal. SCIDs are rare, affecting roughly one infant in 58,000. Over 200 different forms of SCID have been identified.

SCIDs cause severe problems with the development of the immune system, which plays an important role in recognizing potentially dangerous microorganisms and destroying them. In a normal immune system, white blood cells called T cells play many important roles in battling these microorganisms. Another type of white blood cell called B cells also participate in defense, particularly by secreting antibodies.

In people with SCIDs, T cells (and sometimes B cells) fail to work properly. This causes problems with a variety of the body’s immune mechanisms, including your body's ability to respond quickly to previously encountered organisms. Because of these defects in immune cells, people with SCIDs are very susceptible to certain forms of infection.

In the 1970s and 80s, the term “bubble boy disease” became popularized due to a famous child with a SCID who lived for most of his shortened life in a plastic bubble (to protect him from microorganisms). However, treatments for these conditions have radically improved since this time.

Symptoms

The immune system problems of SCIDs can cause various symptoms due to the body’s impaired immune system. Children born with a SCID usually appear healthy at birth. During early infancy, the child has partial protection from certain illnesses because of antibodies it has received from the mother. However, this protection lessens over time. These infants are predisposed to severe viral, bacterial, and fungal infections, as the body has trouble fighting off these microorganisms.

Common symptoms and problems during the first year of life include:

  • Oral fungal infection (oral candidiasis or more severe infections)
  • Recurring and persistent gastrointestinal infections (causing problems like diarrhea)
  • Failure to gain weight normally (usually after a period of normal weight gain)
  • Recurring and persistent lung infections (causing symptoms like cough and congestion)
  • Other bacterial infections (causing middle ear infections, pneumonia, or other problems)
  • Graft versus host disease

Unfortunately, sometimes these infections are severe and fatal.

Depending on the exact type of SCID, certain symptoms and types of infections are more likely to occur. That’s because the immune impairment isn’t identical in all cases of SCID. For example, in “classic SCID,” these problems usually begin during the first year of life. In people with “atypical SCID,” problems usually aren’t quite as severe and they don’t usually become obvious until later.

Depending on the exact genetic cause of the SCID, extra symptoms may occur as well. For example, in a type of SCID known as Omenn syndrome, the following symptoms are also common:

  • Thickened, red rash
  • Hair loss
  • Enlargement of the spleen and liver

Causes

People with a SCID lack functioning T lymphocytes, a type of immune system cell. In some people with SCIDs, B lymphocytes are also impaired. Another group of important immune cells, called natural killer cells, also work poorly in some people with a SCID. These problems with cells of the immune system cause the body to respond very poorly to various infections. 

Ultimately, SCIDs are caused by genetic defects—problems with the genes inherited from one's parents. Researchers have identified mutations in several different genes that can lead to SCIDs. Some of these genes are necessary for the normal maturation of T cells. A protein normally produced by the affected gene might not work properly, preventing the T cell from developing into a normal immune cell. Other types of genes might play an important role in the survival of T cells or B cells. Problems with these genes can cause a person to have dramatically reduced immune function. Researchers are still working to identify the specific genetic causes of certain types of SCID.

You might hear SCID called a primary immunodeficiency. That means that it arises from problems with the immune system that are due to genetic problems present from birth. This contrasts with secondary immunodeficiencies, problems with the immune system that come from environmental factors (like becoming infected with HIV).

Some other types of primary immunodeficiency diseases cause more minor problems with susceptibility to infection. SCIDs are some of the most severe forms of primary immunodeficiency.

How Different Diseases Can Make Your Body Immunocompromised

Diagnosis

It’s very important that children with a SCID be diagnosed as quickly as possible.

Without treatments to improve the child’s immune system, children with a SCID usually die within the first two years of life from a fatal infection.

SCIDs are diagnosed based on clinical exam, medical history, family history, and laboratory tests. A key test is a blood test for the number of T cells present. In people with a SCID, this number is much lower than normal. Genetic testing may be needed to confirm the diagnosis and to find the specific SCID subtype.

Other blood tests may be needed to test for infection and assess general organ function. For example, it is important to rule out HIV infection as the possible cause of symptoms. Children with atypical forms of SCID may take longer to diagnose because their clinical and laboratory findings are not as easy to distinguish.

In most U.S. states and in some countries around the world, infants are screened for SCIDs at birth along with screening for other rare and severe genetic diseases. This enables infants to be identified and treated as quickly as possible. However, not all newborns receive such early screening tests for SCIDs. 

The Prevalence of Immunocompromised Kids

Treatment

Infants with a SCID need specialized treatment by a doctor with experience treating these rare conditions.

Currently, there is only one treatment that can potentially cure most forms of SCID: allogeneic (from a donor) hematopoietic stem cell transplantation (HSCT). Depending on the circumstances, these stem cells are taken from a bone marrow donation through a specific type of blood donation, or via blood taken from the umbilical cord. Prior to the procedure, the affected individual receives chemotherapy to help prepare them to receive new stem cells. Then the person with a SCID receives stem cells that have been taken from a donor (often a relative). The idea is that these stem cells can mature into normal T and B immune cells, curing the individual of their SCID.

The ideal donor of stem cells is a sibling who shares specific genetic similarities with the affected infant (known as an HLA match). However, HSCT may still be an option even if a sibling or other relative with an exact HLA match is not available. This might use stem cells from a non-related donor, or it might use a donation from a relative with only a partial HLA match. If the treatment is initially successful, affected persons can usually live normal lives without ongoing medication.

Gene therapy and enzymatic therapy are currently available for certain forms of SCID with specific genetic causes. For example, both gene therapy and enzymatic treatments are available to people with SCID due to a mutation in a gene known as ADA. Like HSCT, gene therapy is a potentially curative treatment. It may particularly be a good option if an HLA match for HSCT is not available. Enzymatic therapy is another potential option for certain types of SCID, but it requires lifelong therapy. HSCT is likely to remain the key treatment for most types of SCID.

Before HSCT occurs, it is important to do everything possible to prevent infection. It may be necessary to reduce the number of people involved in the care of infants with HSCT, and health care providers may need to take special precautions to help prevent illness. Infants may need to avoid certain types of vaccines which contain live viruses. Sometimes antibiotics are given even before an infection occurs in order to help prevent it. Infusions of antibodies may also be given to temporarily boost immunity.

Children with a SCID also need treatment for infections when they do occur. This may involve a variety of interventions, like the following:

  • Antibiotics
  • Antifungal drugs
  • Intravenous fluids
  • Intravenous feedings for nutritional support
  • Artificial ventilatory care and support in the neonatal intensive care unit

Inheritance

SCIDs are genetic diseases and they can run in families. Some forms of the disease are autosomal recessive, meaning a person has to receive a copy of an affected gene from both their mother and their father. People with only one affected gene (called carriers) do not have the condition. If a couple has had one child born with this kind of SCID, there is a one in four chance that their next child will also have that SCID.

Other forms of SCID are sex-linked. For these forms, an affected female receives two affected genes: one from her mother and one from her father. Boys, however, only need to receive one affected gene to get the disease. For example, an unaffected mother who is a carrier of a SCID might pass the disease to her son. Such a woman would have a 50 percent chance that her next boy would also have SCID. However, a future daughter would be extremely unlikely to have a SCID. These particular forms of SCID are much more common in boys than in girls.

It can be very helpful to talk to a genetic counselor about the risks in your particular situation. In some cases, prenatal testing may be available.

How Genetic Disorders Are Inherited

A Word From Verywell

SCIDs are very serious conditions. Understandably, it can be overwhelming to learn that your child has a potentially fatal disease. However, a team of health professionals are available to help you and your child through this difficult time. It’s reassuring to know that a high percentage of infants who receive treatment do survive. Don’t hesitate to reach out to friends, family members, and other families who have been affected by SCIDs. This can help give you the strength and knowledge you need to make the best health decisions for your family. 

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