National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

X-linked severe combined immunodeficiency


Other Names:
X-linked SCID; Severe combined immunodeficiency, X-linked; SCID, X-linked; X-linked SCID; Severe combined immunodeficiency, X-linked; SCID, X-linked; Severe combined immunodeficiency T- B+ due to gamma chain deficiency; Severe combined immunodeficiency, X-linked, T cell-negative, B cell-positive, NK cell-negative; SCIDX1; XSCID; X-SCID; SCIDX; Severe combined immunodeficiency T- B+, X-linked See More
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X-linked severe combined immunodeficiency (X-SCID) is a severe, genetic condition of the immune system.[1] Signs and symptoms often become apparent in early infancy and include failure to thrive; oral/diaper candidiasis (yeast infection); absent tonsils and lymph nodes; recurrent, persistent infections; rashes; diarrhea; fevers; and pneumonia. X-SCID is caused by mutations in the IL2RG gene and is inherited in an X-linked recessive manner; it only affects males. The condition is typically fatal in the first two years of life unless treated with a bone marrow transplant or gene therapy.[1][2]
Last updated: 5/28/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Decreased lymphocyte proliferation in response to mitogen 0031381
Decreased proportion of CD4-positive helper T cells 0005407
Decreased proportion of naive T cells 0031397
Pneumonia 0002090
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever
[ more ] 		0001954
Reduced natural killer cell count 0040218
30%-79% of people have these symptoms
Abnormally low T cell receptor excision circle level 0031545
Cough
Coughing
0012735
Decreased circulating IgA level 0002720
Decreased circulating IgG level 0004315
Decreased proportion of CD3-positive T cells 0045080
Diarrhea
Watery stool
0002014
Recurrent opportunistic infections 0005390
Sepsis
Infection in blood stream
0100806
Skin rash 0000988
5%-29% of people have these symptoms
Absent tonsils 0030813
Chronic oral candidiasis
Chronic oral thrush
0009098
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Lymph node hypoplasia 0002732
Recurrent bacterial skin infections 0005406
Recurrent Haemophilus influenzae infections 0005376
Recurrent herpes
Susceptibility to herpesvirus
0005353
Severe recurrent varicella 0005428
1%-4% of people have these symptoms
Hepatomegaly
Enlarged liver
0002240
Increased circulating IgG level 0003237
Jaundice
Yellow skin
Yellowing of the skin
[ more ] 		0000952
Lymphoma
Cancer of lymphatic system
0002665
Lymphoproliferative disorder 0005523
Percent of people who have these symptoms is not available through HPO
Agammaglobulinemia 0004432
Chronic diarrhea 0002028
Hypoplasia of the thymus
Small thymus
0000778
Recurrent bacterial meningitis 0007274
Recurrent fungal infections 0002841
Severe combined immunodeficiency 0004430
X-linked recessive inheritance 0001419
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Last updated: 7/1/2020
X-linked severe combined immunodeficiency (X-SCID) is inherited in an X-linked recessive manner.[2] A condition is X-linked if the changed (mutated) gene responsible for the condition is located on the X chromosome. The X chromosome is one of the two sex chromosomes; females have two X chromosomes, and males have one X and one Y chromosome. In males, one mutated copy of the responsible gene causes signs and symptoms of the condition because they don't have another X chromosome with a working copy of the gene. In females, having one mutated copy of the gene would make them an unaffected carrier; a mutation would have to occur in both copies of the gene to cause the condition. This is why X-linked recessive disorders, including X-linked SCID, occur much more frequently in males. In female infants who have symptoms of SCID, non-X-linked forms of SCID (autosomal recessive forms) should be considered.[2]

The father of a boy with X-SCID cannot have the disease and cannot be a carrier (having a mutated copy of the responsible gene would make him affected). If an affected boy is the only affected family member, either his mother is a carrier or the mutation occurred for the first time in the affected boy (a de novo mutation). It is thought that about 2/3 of these cases are inherited from a carrier mother, and about 1/3 are due to new de novo mutations.[2]

If there is more than one affected family member, it is assumed that the mother of the affected boy is a carrier. A carrier mother has a 50% risk to pass on the mutation in each pregnancy. Males who inherit the mutation will be affected, and females who inherit the mutation will be unaffected carriers. A man with X-SCID will pass the mutation to all of his daughters and none of his sons.[2] 

Genetic testing can often determine which family member had the first mutation. Identifying this family member is important for learning which branches of a family are at risk for X-SCID. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing IL2RG mutation has been identified in the family.[2]

People with a family history of X-SCID who are interested in learning about genetic risks to themselves and family members should speak with a genetics professional.
Last updated: 5/27/2014

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to X-linked severe combined immunodeficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with X-linked severe combined immunodeficiency. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for X-linked severe combined immunodeficiency:
    European Society for Immunodeficiencies (ESID) Registry
    United States Immunodeficiency Network (USIDENT) Registry
     
  • The Primary Immune Deficiency Treatment Consortium (PIDTC) is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with severe combined immunodeficiency, Wiskott-Aldrich syndrome, and chronic granulomatous disease through research. The Primary Immune Deficiency Treatment Consortium (PIDTC) has a registry for patients who wish to be contacted about clinical research opportunities.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The American Society of Gene & Cell Therapy provides information on the treatment of immunodeficiency diseases.
  • Genetics Home Reference (GHR) contains information on X-linked severe combined immunodeficiency. This website is maintained by the National Library of Medicine.
  • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss X-linked severe combined immunodeficiency. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • In the case of X-linked SCID, if a girl has SCID it means she inherited a defective X gene from both parents. But if the father has a defective X gene, he would have to be affected with SCID. How can a father just be a carrier in the case of an affected daughter? And what is the risk in a subsequent pregnancy to have SCID if both parents are carriers? Is it possible for a male to be a carrier? See answer


  1. X-linked severe combined immunodeficiency. Genetics Home Reference. 2009; http://ghr.nlm.nih.gov/condition/x-linked-severe-combined-immunodeficiency. Accessed 8/8/2011.
  2. Eric Allenspach, David J Rawlings, and Andrew M Scharenberg. X-Linked Severe Combined Immunodeficiency. GeneReviews. January 24, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1410/. Accessed 5/28/2014.