Severe combined immunodeficiency

Información en español Title

Other Names:

SCID

Categories:

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

Subtypes:

Adenosine deaminase deficiency; DOCK2 Deficiency; Severe combined immunodeficiency with sensitivity to ionizing radiation; Adenosine deaminase deficiency; DOCK2 Deficiency; Severe combined immunodeficiency with sensitivity to ionizing radiation; Severe combined immunodeficiency, atypical; X-linked severe combined immunodeficiency 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, children with SCID 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 common type of SCID is called X-linked severe combined immunodeficiency (XSCID). Another form of SCID is caused by a deficiency of the enzyme adenosine deaminase (ADA).^[1] Infections are treated with specific antibiotic, antifungal, and antiviral agents and administration of intravenous (IV) immunoglobulin.^[2] The most effective treatment is transplantation of blood-forming stem cells from the bone marrow of a healthy person.^[1]

Last updated: 6/28/2017

Symptoms 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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Chronic diarrhea		0002028
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Fever		0001945
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Sepsis		0100806
Severe combined immunodeficiency		0004430
30%-79% of people have these symptoms
Alopecia	Hair loss	0001596
Lymphopenia	Decreased blood lymphocyte number Low lymphocyte number [ more ]	0001888
Skin rash		0000988
5%-29% of people have these symptoms
Abnormality of the dentition	Abnormal dentition Abnormal teeth Dental abnormalities Dental abnormality [ more ]	0000164
Chronic otitis media	Chronic infections of the middle ear	0000389
Hepatomegaly	Enlarged liver	0002240
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Recurrent urinary tract infections	Frequent urinary tract infections Urinary infection Urinary tract infection Urinary tract infections Urinary tract infections, recurrent [ more ]	0000010
Sensorineural hearing impairment		0000407
Splenomegaly	Increased spleen size	0001744

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2018

Do you have updated information on this disease? We want to hear from you.

Inheritance Inheritance

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 genetic disorder is X-linked if the disease-causing gene is 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 disease-causing gene causes signs and symptoms of the disorder because they do not have another X chromosome with a working copy of the gene. In females, having one copy of the disease-causing gene would make them a carrier without the genetic disorder; a mutation would have to occur in both copies of the gene to cause the disorder. 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 disorders 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 disease-causing genes on other chromosomes (not the sex chromosomes). In autosomal recessive genetic disorders, a person must have mutations in both copies of the disease-causing gene in order to have signs or symptoms of the disorder. In most cases, the affected person inherits one disease-causing copy of the gene from each of the parents, who are typically carriers with no signs and symptoms of the genetic disorder.

Last updated: 6/28/2017

Diagnosis Diagnosis

A diagnosis of SCID may be suspected if a baby shows any of the following persistent symptoms within the first year of life:^[3]

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 (IV) 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

A diagnosis can be confirmed by blood tests. Blood tests show significantly lower-than-normal levels of T cells and antibodies.^[3]

Since there are other conditions that can result in lower-than-normal numbers of the different types of lymphocytes, the most important tests are those of T-cell function by placing blood lymphocytes in culture tubes, and treating them with various stimulants. Normal T-lymphocytes react to these stimulants by undergoing cell division. In contrast, lymphocytes from patients with SCID usually do not react to these stimuli.

Immunoglobulin levels are usually very low in SCID. Most commonly (but not always), all immunoglobulin classes are depressed (IgG, IgA, IgM and IgE).

The diagnosis of SCID can also be made before the baby is born if there has been another infant in the family with the disorder and if the gene defect has been identified. If genetic analysis had been completed on the infant in the family with SCID, a diagnosis can be determined during subsequent pregnancies. This can be done by molecular testing of cells from a chorionic villous sampling (CVS) or from an amniocentesis, where a small amount of amniotic fluid (which contains fetal cells) is removed.

Early diagnosis, before the infant has had a chance to develop any infections, is very valuable since bone marrow transplants given in the first three months of life have a 94% success rate. In fact, screening newborns to detect SCID soon after birth has been made possible because of recent scientific advances. Approximately half of the babies born in the U.S. are now being screened for SCID.

Last updated: 6/28/2017

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

Treatment Treatment

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 Lediant Biosciences
FDA-approved indication: For enzyme replacement therapy for ADA deficiency in patients with severe combined immunodeficiency.
National Library of Medicine Drug Information Portal
Immune globulin intravenous (human), 10% liquid (Brand name: Privigen) - Manufactured by CSL Behring
FDA-approved indication: For the treatment of adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment, however not studied for use longer than 6 months. Also for the treatment of patients age 15 years and older with chronic immune thrombocytopenic purpura (ITP) to raise platelet counts, and as replacement therapy for primary humoral immunodeficiency (PI).
National Library of Medicine Drug Information Portal

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other combined B-cell and T-cell disorders, 22q11.2 deletion syndrome, congenital TORCH infection, X-linked or autosomal recessive agammaglobulinemia, and other forms of hypogammaglobulinemia (see these terms). Visit the Orphanet disease page for more information.

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 related to 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

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

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)
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/
Immune Deficiency Foundation
110 West Road, Suite 300
Towson, MD 21204
Toll-free: 800-296-4433
Fax: 410-321-9165
E-mail: idf@primaryimmune.org
Website: http://www.primaryimmune.org/
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/
United States Immunodeficiency Network (USIDNET)
Towson, MD 21204-4803
Toll-free: 800-296-4433 (se habla español)
Fax: 410-321-9165
E-mail: info@usidnet.org
Website: http://www.usidnet.org

Do you know of an organization? We want to hear from you.

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

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.
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

News

NCATS Rare Diseases Are Not Rare! Challenge
October 9, 2018
The NIH Undiagnosed Diseases Network Expands
September 26, 2018
From a Single Genetic Mutation, Secrets of ‘Boy in the Bubble’ Disease Revealed
January 5, 2017

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

Have a question? Contact a GARD Information Specialist.