Severe combined immunodeficiency

Title

Other Names:

SCID; Bubble boy disease; ADA deficiency; SCID; Bubble boy disease; ADA deficiency; Severe combined immunodeficiency due to adenosine deaminase deficiency See More

Categories:

Congenital and Genetic Diseases; Immune System Diseases; Metabolic disorders; Congenital and Genetic Diseases; Immune System Diseases; Metabolic disorders; RDCRN See More

Summary Summary

Severe combined immunodeficiencies (SCID) are inherited immune system disorders characterized by abnormalities with responses of both T cells and B cells (specific types of white blood cells needed for immune system function). Common signs and symptoms include an increased susceptibility to infections including ear infections; pneumonia or bronchitis; oral thrush; and diarrhea. Due to recurrent infections, affected children do not grow and gain weight as expected (failure to thrive). SCID may be caused by mutations in any of several genes and can be inherited in an X-linked recessive (most commonly) or autosomal recessive manner. The most effective treatment is transplantation of blood-forming stem cells from the bone marrow of a healthy person. Without treatment, affected children rarely live past the age of two.^[1]

Last updated: 5/27/2014

Inheritance Inheritance

Severe combined immunodeficiency (SCID) can be inherited in an X-linked recessive or autosomal recessive manner depending on the genetic cause of the condition. X-linked SCID is the most common type of SCID and is inherited in an X-linked recessive manner.

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 chromosome 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. Because fathers only pass their Y chromosome on to their sons, fathers cannot pass X-linked conditions on to their sons.

The other, less common causes of SCID are inherited in an autosomal recessive manner. These types are due to mutations in responsible genes on other chromosomes (not the sex chromosomes). In autosomal recessive conditions, a person must have mutations in both copies of the responsible gene in order to have signs or symptoms of the condition. In most cases, the affected person inherits one mutated copy of the gene from each of the parents, who are typically unaffected carriers.

Last updated: 5/27/2014

Diagnosis Diagnosis

A diagnosis of severe combined immunodeficiency (SCID) may be suspected if a baby shows any of the following persistent symptoms within the first year of life:^[2]

Eight or more ear infections
Two or more cases of pneumonia
Infections that do not resolve with antibiotic treatment for two or more months
Failure to gain weight or grow normally
Infections that require intravenous antibiotic treatment
Deep-seated infections, such as pneumonia that affects an entire lung or an abscess in the liver
Persistent thrush in the mouth or throat
A family history of immune deficiency or infant deaths due to infections

Diagnosis can be confirmed by blood tests. Blood tests show significantly lower-than-normal levels of T cells and antibodies.^[2]

For further details on diagnosis see the following Web pages:

The Primary Immunodeficiency Resource Center provides further details regarding diagnosis of SCID. Click on the embedded link to view the page.

An article from Medscape Reference provides detailed information on the diagnosis of SCID. Click on eMedicine Journal to view the page. You may need to register to view the article, but registration is free.

Last updated: 5/28/2014

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.
Bonilla, Francisco A. Development of Population-Based Newborn Screening for Severe Combined Immunodeficiency. Pediatrics 2006;118:S47.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

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.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Pegademase bovine (Brand name: Adagen®) - Manufactured by Enzon, Inc.
FDA-approved indication: For enzyme replacement therapy for ADA deficiency in patients with severe combined immunodeficiency.
National Library of Medicine Drug Information Portal

Research Research

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 studying or have studied Severe combined immunodeficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Patient Registry

Primary Immunodeficiency Diseases Registry (PIDR)
Toll-free: 1-800-296-4433
Web site: Primary Immunodeficiency 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.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Suggest an organization to add.

Organizations Supporting this Disease

Canadian Immunodeficiencies Patient Organization (CIPO)
362 Concession Road 12
RR #2
Hastings Ontario K0L 1Y0
Canada
Telephone: 877-262-2476 (toll-free)
Fax: 866-942-7651 (toll-free)
E-mail: info@cipo.ca
Website: http://cipo.ca
Immune Deficiencies Foundation Australia
PO Box 969
Penrith NSW 2751
Australia
Telephone: 800-100-198
E-mail: info@idfa.org.au
Website: http://www.idfa.org.au/
International Patient Organization for Primary Immunodeficiencies (IPOPI)
Firside Main Road
Downderry
Cornwall PL11 3LE
United Kingdom
Telephone: 44-01503-250-668
E-mail: Info@ipopi.org
Website: http://www.ipopi.org/
National Primary Immunodeficiency Resource Center
747 Third Avenue
New York, NY 10017
Toll-free: 800-533-3844
Telephone: 212-819-0200
Fax: 212-764-4180
E-mail: info@jmfworld.org
Website: http://www.info4pi.org
United States Immunodeficiency Network (USIDNET)
Towson, MD 21204-4803
Toll-free: 800-296-4433
Fax: 410-321-9165
E-mail: info@usidnet.org
Website: http://www.usidnet.org

Living With Living With

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

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More 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 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

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.
The 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 Severe combined immunodeficiency. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Kaufman, et al. Cerebral Lymphoma in an Adenosine Deaminase-Deficient Patient With Severe Combined Immunodeficiency Receiving Polyethylene Glycol-Conjugated Adenosine Deaminase. Pediatrics 2005;116:e876-e879.

News & Events News & Events

NCATS Co-Sponsored Conferences

The Jak/Stat Pathway: 20 Years from Discovery to Drugs Thursday, September 22, 2011 - Saturday, September 24, 2011
Location: NIH Natcher Center, Bethesda, MD
Description: As a scientific conference, the primary goal is the dissemination of recent data and developments in the field to intersted researchers in the field. The conference includes a scientific program and reception, which will help to foster collaboration and networking. Participants should achieve a better understanding of the state of the art research in this exciting and clinically relevant field.

Contact: Megan Laycock,(301) 594-7527Megan.laycock@nih.gov

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Rare Diseases Research
- Agenda ( - 49KB)
Primary Immune Deficiency Treatment Consortium (PIDTC) Scientific Workshop Thursday, April 7, 2011 - Saturday, April 9, 2011
Location: San Francisco, CA
Description: This was a 3-day meeting. Participation at the workshop was by invitation and included representatives from each of the centers participating at PIDTC as well as representatives of CIBMTR, USIDNET, NIAID, ORDR, EBMT, and ESID. This was meant to favor collaboration and promote international collaborative trials in the field of these rare disorders. Special attention was paid to invitation of young investigators at a senior stage in their training or at the beginning of their academic careers. The meeting was open to representatives of the patient advocacy groups that are active in the field of primary immune deficiencies (PIDs) with the intent of promoting communication and collaboration. The results of the meeting will be published in a peer-reviewed journal.

Contact: Nancy Coulter,(301) 496-1886, ncoulter@niaid.nih.gov

Co-funding Institute(s): National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research
- Participants ( - 183KB)
Fifth International Meeting of Gene and Cell Therapies for Arthritis and Related Diseases Tuesday, April 29, 2008 - Thursday, May 1, 2008
Location: Bell Harbor Conference Center, Seattle, WA
Description: The goals of this meeting were to share advances in cellular biology that offer the opportunity to harness regulatory immune cells to combat autoimmune disease, to harness the use of multipotent progenitor cells to augment tissue regeneration and repair, and to accelerate the development of molecular and cellular therapies for rheumatologic and orthopaedic disorders. The GTARD conference series was initiated 9 years ago as a dedicated forum for investigators performing research in these areas to review and discuss scientific progress and to share ideas and technologies. Proceedings from the first three meetings have been published and proceedings from the 2006 meeting are currently in revision. The proceedings from this meeting will be similarly published.

Contact: Dr. Theresa Smith, NIAMS(301) 435-5595smiththe@mail.nih.gov

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Agenda ( - 119KB)
- Summary ( - 65KB)
Workshop on Registries for Primary Immunodeficiency Diseases Tuesday, November 19, 1996
Location: NIH Campus, Bethesda, MD
Contact: Dr. Howard Dickler(301) 496-7104

Co-funding Institute(s): National Institute of Allergy and Infectious Diseases

Related Diseases Related Diseases

The following diseases are related to Severe combined immunodeficiency. If you have a question about any of these diseases, you can contact GARD.

GARD Answers GARD Answers

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
My baby has low CD3 and CD4 cells. I have consulted a hematologist and was told it is doubtful my baby has SCID. When can we consider it is SCID? See answer

References References

Learning About Severe Combined Immunodeficiency (SCID). NHGRI. December 27, 2013; http://www.genome.gov/13014325. Accessed 5/27/2014.
Learning about severe combined immunodeficiency (SCID). National Human Genome Research Institute. July 2010; http://www.genome.gov/13014325. Accessed 8/9/2011.

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