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Disease Profile

Severe combined immunodeficiency due to complete RAG1/2 deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

D81.1

Inheritance

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

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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

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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.

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

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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.

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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.

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Not applicable

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Other names (AKA)

SCID, AR, T-cell negative, B-cell negative, NK cell-positive; SCID due to complete RAG1/2 deficiency; Severe immunodeficiency, autosomal recessive, T-cell negative, B-cell negative, NK cell-positive

Categories

Congenital and Genetic Diseases; Immune System Diseases; Newborn Screening

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 331206

Definition
Severe combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-Bsevere combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound Tand Bcell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia.

Visit the Orphanet disease page for more resources.

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
Abnormal B cell count
0010975
Decreased circulating IgA level
0002720
Decreased circulating IgG level
0004315
Decreased circulating total IgM
0002850
30%-79% of people have these symptoms
Decreased lymphocyte proliferation in response to mitogen
0031381
Decreased proportion of CD3-positive T cells
0045080
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fever
0001945
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number

[ more ]

0001888
Protracted diarrhea
0004385
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections

[ more ]

0002718
Recurrent enteroviral infections
0002743
Recurrent fungal infections
0002841
Recurrent upper and lower respiratory tract infections
0200117
Reduced antigen-specific T cell proliferation
0031402
5%-29% of people have these symptoms
Abnormal natural killer cell count
0040089
Autoimmune hemolytic anemia
0001890
Elevated hepatic transaminase
High liver enzymes
0002910
Eosinophilia
High blood eosinophil count
0001880
Hepatomegaly
Enlarged liver
0002240
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Lymphadenitis
Inflammation of the lymph nodes
0002840
Pallor
0000980
Skin rash
0000988
Thrombocytopenia
Low platelet count
0001873
Percent of people who have these symptoms is not available through HPO
Arthritis
Joint inflammation
0001369
Autosomal recessive inheritance
0000007
B lymphocytopenia
Low B cell count
0010976
Conjunctivitis
Pink eye
0000509
Diarrhea
Watery stool
0002014
Failure to thrive secondary to recurrent infections
Faltering weight secondary to recurrent infections
Weight faltering secondary to recurrent infections

[ more ]

0008866
Mastoiditis
0000265
Meningitis
0001287
Otitis media
Middle ear infection
0000388
Panhypogammaglobulinemia
0003139
Pneumonia
0002090
Purulent rhinitis
0040334
Recurrent opportunistic infections
0005390
Severe combined immunodeficiency
0004430
T lymphocytopenia
Low T cell count
Reduced number of T cells

[ more ]

0005403

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.

    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

      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

      • MedlinePlus Genetics contains information on Severe combined immunodeficiency due to complete RAG1/2 deficiency. 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.
        • 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.

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