Combined immunodeficiency due to partial RAG1 deficiency

Title

Other Names:

CID due to partial RAG1 deficiency; CID with expansion of gamma delta T cells; Combined immunodeficiency with expansion of gamma delta T cells; CID due to partial RAG1 deficiency; CID with expansion of gamma delta T cells; Combined immunodeficiency with expansion of gamma delta T cells; Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity See More

Summary Summary

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

Orpha Number: 231154

Disease definition

Combined immunodeficiency due to partial RAG1 deficiency is a form of combined T and B cell immunodeficiency (CID; see this term) characterized by severe and persistent cytomegalovirus (CMV) infection and autoimmune cytopenia.

Epidemiology

Prevalence is unknown. To date, 9 cases have been reported.

Clinical description

Patients present before the age of one year with severe disseminated CMV infection, which can manifest with fever and splenomegaly, and recurrent and severe co-infections including sepsis and pneumonitis. Autoimmune cytopenia also occurs and can include autoimmune hemolytic anemia (see these terms) or neutropenia.

Etiology

SCID due to partial RAG1 deficiency is caused by hypomorphic mutation in the RAG1 gene (11p13). This results in oligoclonal expansion of T cell receptor (TCR) gamma-delta T cells and TCR alpha-beta T cell lymphopenia, although total lymphocyte counts are normal, in combination with CMV infection and autoimmunity.

Diagnostic methods

Diagnosis is based on clinical evaluation, immunological investigation, including lymphocyte subset phenotyping, lymphocyte proliferation to mitogen stimulation, immunoglobulin levels and antibody response to vaccine antigens, and genetic confirmation.

Differential diagnosis

Differential diagnoses include other combined immunodeficiencies.

Antenatal diagnosis

Prenatal diagnosis can be performed in families where there is a family history and in which the genetic mutation has been identified.

Genetic counseling

Transmission is autosomal recessive.

Management and treatment

Treatment involves antiviral treatment and management of recurrent infections. Bone marrow transplant has been attempted but may result in graft versus host disease (GVHD; see this term) associated with reactivation of CMV disease. Patients should be treated in centers with experience of transplanting complex primary immunodeficiencies.

Prognosis

The majority of patients reported to date have died within the first few years of life.

Visit the Orphanet disease page for more resources.

Last updated: 7/1/2012

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
B lymphocytopenia	Low B cell count	0010976
Decrease in T cell count	Low T cell count Reduced number of T cells [ more ]	0005403
Interstitial pneumonitis		0006515
Sepsis	Infection in blood stream	0100806
Severe combined immunodeficiency		0004430
Splenomegaly	Increased spleen size	0001744
30%-79% of people have these symptoms
Autoimmune hemolytic anemia		0001890
Neutropenia in presence of anti-neutropil antibodies		0001904

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

Last updated: 4/1/2019

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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.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Combined immunodeficiency due to partial RAG1 deficiency. 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 Combined immunodeficiency due to partial RAG1 deficiency:
United States Immunodeficiency Network (USIDENT) Registry

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.

In-Depth Information

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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