X-linked severe combined immunodeficiency

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Disease Profile

1-9 / 100 000

US Estimated

Europe Estimated

Age of onset

Neonatal

ICD-10

D81.2

Inheritance

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.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

X-linked SCID; Severe combined immunodeficiency, X-linked; SCID, X-linked;

Summary

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]

Symptoms

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.

Medical Terms	Other Names	Learn More: 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
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Jaundice	Yellow skin Yellowing of the skin [ more ]	0000952
Lymphoma	Cancer of lymphatic system	0002665
Lymphoproliferative disorder		0005523
Neonatal onset		0003623
Recurrent pneumonia		0006532
Percent of people who have these symptoms is not available through HPO
Agammaglobulinemia		0004432
Chronic diarrhea		0002028
Decreased circulating IgE		0005479
Decreased circulating total IgM		0002850
Hypoplasia of the thymus	Small thymus	0000778
Impaired lymphocyte transformation with phytohemagglutinin		0003347
Recurrent bacterial meningitis		0007274
Recurrent fungal infections		0002841
Reduced natural killer cell activity		0012178
Severe combined immunodeficiency		0004430
T lymphocytopenia	Low T cell count Reduced number of T cells [ more ]	0005403
X-linked recessive inheritance		0001419

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Diagnosis

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.

Organizations

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

Canadian Immunodeficiencies Patient Organization (CIPO)
25 La Grave St
Winnepeg, MB
R3V 1J1 Canada
Telephone: 877-262-2476 (toll-free)
Fax: 866-942-7651 (toll-free)
E-mail: https://www.cipo.ca/#contact
Website: https://cipo.ca
Immune Deficiencies Foundation Australia
PO Box 969
Penrith NSW 2751
Australia
Telephone: 800-100-198
E-mail: [email protected]
Website: https://www.idfa.org.au/
International Patient Organization for Primary Immunodeficiencies (IPOPI)
Rock Bottom, Trerieve
Downderry
PL11 3LY
United Kingdom
Telephone: 44-01503-250-668/961
E-mail: [email protected]
Website: https://ipopi.org

Organizations Providing General Support

Primary Immune Deficiency UK (PID UK)
PO Box 6970
Basingstoke, RG24 4XL United Kingdom
Toll-free: 0800 987 8986
E-mail: [email protected]
Website: https://www.piduk.org/

Learn more

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

Simons, E. Gene Therapy of X-Linked Severe Combined Immunodeficiency by Use of a Pseudotyped Gammaretroviral Vector. Pediatrics 2006; 118: S48-S49.

References

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

Rare Immunology News

Rare Immunology News

Rare Immunology News

Neonatal

D81.2

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Diagnosis

Testing Resources

Newborn Screening

Organizations

Organizations Supporting this Disease

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

Selected Full-Text Journal Articles

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.