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Disease Information

Inherited Immunodeficiencies: Severe Combined Immunodeficiency Disorder (SCID)

Alternate Names: SCID

Definition

Severe combined immunodeficiency (SCID) is an inherited disorder of the immune system that can affect males or females. It is characterized by an unusual susceptibility to infections. There are at least five types of SCID that have been described and all are a result of a mutation (mistake) in one of five different genes. Approximately half of all cases of severe combined immunodeficiency  are seen in males. This is because the most common form of SCID is passed on from the mother to male children (XSCID).
 
Patients with severe combined immunodeficiency  have poor or absent function of certain types of white blood cells. The cells affected are T cells and B cells, hence the term combined. In the normal individual, T cells are responsible for providing protection against certain viral and fungal infections.  B cells are precursors to antibody producing cells. The diagnosis of SCID is confirmed by mutation detection (laboratory test looking for a mistake in the gene).

Incidence

Severe combined immunodeficiency occurs with a frequency of about 3-4/million live births.

Influencing Factors

Pattern of Inheritance for X-linked SCID (XSCID)
The gene for the most common form of severe combined immunodeficiency is found on the X chromosome (XSCID).  Because females have two X chromosomes, if they have a mutation on one X chromosome, they have a spare X that can help compensate for the mutation.  Males have only one X chromosome and one Y chromosome.  Since they do not have a spare X chromosome, they show signs of a mutation inherited on the X chromosome.  Although a female who carries the mutation for XSCID on one of her X chromosomes shows no signs of immunodeficiency, her sons and daughters have a 50 percent chance of inheriting the X chromosome with the mutation (and a 50 percent chance of inheriting the normal X chromosome).  The sons who inherit the mutant X chromosome will have XSCID and the daughters who inherit the mutant X chromosome will be carriers like their mother.  Carriers of XSCID can be identified by mutation detection (laboratory test).

All of the daughters of a man with XSCID will be carriers of XSCID; but the sons, who have inherited his unaffected Y chromosome, will be normal.  About 50 percent of patients with XSCID will have a brother, cousin or uncle with XSCID.  In most remaining families, the affected individual represents the first sign of a new mutation (mistake) in the XSCID gene in his family.  We do not know what causes new mutations in most families.

Pattern of inheritance for autosomal recessive SCID (ARSCID)
As previously noted, the most common form of severe combined immunodeficiency is inherited in an X-linked pattern and affects only males. The remaining types of SCID are inherited in an autosomal recessive pattern and affect males and females equally (ARSCID). This form of SCID occurs if two abnormal genes, one from each parent, are present in the patient. Each parent carries an abnormal gene but does not have any physical symptoms of the disorder itself.

For each pregnancy, there is a 25 percent chance of having an unaffected child, a 25 percent chance that the child will inherit the problem and a 50 percent chance that the child will be a carrier, like their parents, for ARSCID. Each pregnancy carries the same risks or chance, and one pregnancy is not influenced by another.

Clinical Features and Symptoms

Children with severe combined immunodeficiency usually develop symptoms in the first two to seven months of life. Typically they fail to gain weight and do not grow normally. They may have persistent diarrhea, upper respiratory symptoms and a fungal infection of the mouth (thrush) and diaper area that doesn’t respond to typical treatments or medicines given for these symptoms. 

A life threatening pneumonia can also be seen which is caused by the organism (germ)  pneumocystis carinii (PCP) and often leads to the diagnosis of an immune system disorder. In normal individuals, this organism does not lead to serious disease, but in SCID can be fatal if left untreated. Meningitis and bloodstream infections can also be seen.

Survival Rates

The prognosis for severe combined immunodeficiency  has improved due to the success of bone marrow transplants and the use of antibiotics and intravenous gammaglobulin (IVIG).

Treatment Strategies

Patients with severe combined immunodeficiency  are treated with hematopoietic stem cell transplants (bone marrow transplants). The best donor is a brother or sister who is a match.  If a matched brother or sister is not available, some centers use a parent as a donor, others use a matched unrelated donor and still others use a cord blood.

Prior to bone marrow transplant, patients are kept in isolation to protect them from everyday organisms that could be harmful to their compromised immune systems. They are not allowed to go to public places (day cares, churches, malls, and doctors offices) and most often are kept in the hospital while waiting for transplant.

A child with severe combined immunodeficiency  should NOT receive any immunizations. Specifically, the live vaccines such as oral polio and chicken pox vaccine should be avoided because they are particularly dangerous to the child with SCID. Once diagnosed, IVIG will be given which will help protect the child with SCID from most of the common childhood illnesses.  In addition, siblings of the child with SCID should also avoid being immunized with the live viral vaccines.

Some types of SCID are due to deficiency of an enzyme. These enzymes can be replaced in the form of an injection given once or twice a week.

Gene therapy is also being explored as a treatment option for children with severe combined immunodeficiency  and has been successful in a small number of patients with XSCID. 

Current Research

• Better understanding the role of the severe combined immunodeficiency genes in the normal immune system
• Improving transplant to cure SCID
• Investigating the use of gene therapy to cure SCID
• Identifying other gene defects that result in SCID

 

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