X-linked severe combined immunodeficiency

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What is X-Linked Severe Combined Immunodeficiency?

X-linked severe combined immunodeficiency (X-SCID), caused by harmful genetic changes (mutations) in the IL2RG gene, is a disorder of the immune system that causes recurrent, severe infections, fevers, and skin rashes. The IL2RG gene gives our bodies instructions for making part of a protein called the common gamma chain, which helps our immune system function. Individuals with X-SCID are missing two important immune-system components, T lymphocytes and natural killer lymphocytes. These individuals also have B lymphocytes that do no work. Since the immune system is unable to function properly, individuals with X-SCID are unable to fight off infections.

X-SCID is an X-linked disease which means that the IL2RG gene is on the X chromosome. Males have one copy of the X chromosome and the IL2RG gene, while females have two copies. Because of this, men with a harmful change in IL2RG are affected by X-SCID, while most female carriers still have one working copy of the gene and do not tend to show symptoms. However, there are rare cases reports of female carriers affected by X-SCID.

Symptoms of X-SCID typically begin between three and six months of age. Most infants with untreated X-SCID will show slower than average growth, develop significant diaper and oral rashes, and will have severe, persistent infections despite active treatment. They may also have absent tonsils and lymph nodes. Babies with an atypical form of X-SCID may have immune-system dysfunction, rashes, gastrointestinal problems, and short stature.

How common is X-Linked Severe Combined Immunodeficiency?

The true incidence of X-SCID is unknown. It is thought to occur in at least 1 in 50,000 to 1 in 100,000 male births. X-SCID occurs at a similar frequency amongst all ethnicities, but X-SCID may be more prevalent in the United States due to population structure. More information about the true incidence of the condition may come as other countries adopt newborn screening and registries become more established.

How is X-Linked Severe Combined Immunodeficiency treated?

Bone-marrow transplantation is the most common form of treatment for X-SCID. Replacement of the bone marrow in a person with X-SCID with the bone marrow of a healthy individual allows the body to generate new, functional blood cells and lymphocytes. Bone-marrow transplantation has a significantly higher success rate if performed shortly after birth. Cord blood transplantation may also be an effective treatment of X-SCID. Gene therapy may also be considered for patients that are not good candidates for bone-marrow or cord blood transplantation.

What is the prognosis for an individual with X-Linked Severe Combined Immunodeficiency?

X-SCID is almost universally fatal unless a successful bone-marrow transplantation or gene therapy is completed. Approximately 90% of infants can be successfully treated with a bone-marrow transplant. For infants in which a bone-marrow transplant is not completely successful, or for those who are not candidates for a bone-marrow transplant, administration of proteins to help the immune system function may be beneficial. For infants in whom bone-marrow transplantation, gene therapy, or immunoglobulin infusion is unsuccessful, the average life expectancy is approximately one to two years.