Rare Gastroenterology News

Disease Profile

Combined immunodeficiency due to partial RAG1 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.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

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

no.svg

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

no.svg

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.

no.svg

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

no.svg

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.

no.svg

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.

no.svg

Not applicable

no.svg

Other names (AKA)

CID due to partial RAG1 deficiency; CID with expansion of gamma delta T cells; Combined immunodeficiency with expansion of gamma delta T cells;

Summary

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

Orpha Number: 231154

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.

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
B lymphocytopenia
Low B cell count
0010976
Interstitial pneumonitis
0006515
Sepsis
Infection in blood stream
0100806
Severe combined immunodeficiency
0004430
Splenomegaly
Increased spleen size
0001744
T lymphocytopenia
Low T cell count
Reduced number of T cells

[ more ]

0005403
30%-79% of people have these symptoms
Autoimmune hemolytic anemia
0001890
Neutropenia in presence of anti-neutropil antibodies
0001904

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.