What is X-Linked Severe Combined Immunodeficiency? X-linked severe combined immunodeficiency (X-SCID), caused by harmful genetic changes (variants) 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 critical pieces of the immune system: T lymphocytes and natural killer lymphocytes. These individuals also have B lymphocytes that do not work. Since the immune system cannot function properly, individuals with X-SCID cannot fight off infections. X-SCID is inherited in an X-linked manner. This means the condition is typically more severe in individuals assigned male at birth (XY). Individuals assigned female at birth (XX) usually do not have symptoms of the condition. 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 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. Additional considerations for carriers Most XX individuals (who are typically assigned female at birth) are carriers of X-SCID and do not have symptoms. However, there are rare cases reports of carriers affected by X-SCID. 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 XY individuals. 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 for X-SCID. Gene therapy may also be considered for patients who 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 entirely 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. Other names forX-linked severe combined immunodeficiency SCIDX1 Swiss-type agammaglobulinemia X-linked SCID XSCID References Allenspach et al., 2016, GeneReviews, http://www.ncbi.nlm.nih.gov/books/NBK1410/ Fischer, 2000, Clin Exp Immunol, 122(2):143-9, PMID: 11091267 Puck, 1997, JAMA, 278(22):1835-41, PMID: 9396644