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Disease Profile

Combined immunodeficiency with skin granulomas

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

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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)

CID due to RAG 1/2 deficiency; Combined immunodeficiency due to RAG 1/2 deficiency; Combined immunodeficiency with granulomatosis;

Categories

Congenital and Genetic Diseases; Immune System Diseases; Skin Diseases

Summary

Combined immunodeficiency with skin granulomas is characterized by recurrent viral infections and the presence of granulomas in the skin, mucous membranes and/or internal organs. There is a gradual reduction in the number and function of B cells (a type of white blood cell that makes antibodies), and  T lymphocytes (a type of white blood cell, that protect the body from infection attacking the infected cells directly), hypogammaglobulinemia (reduction in all types of gamma globulins, including antibodies that help fight infection.) and defective autoinmunity where the immune system attacks the body itself.[1] Some people may develop associated auto-immune diseases such as myasthenia gravis, vitiligo, low blood red and white cells, psoriasis, and Guillain–Barré syndrome.[2] 

It is caused by mutations in the RAG1 and/or RAG2 genes.[2] These genes provide instructions for making a member of a group of proteins called the RAG complex, which is involved in the process, known as V(D)J recombination, needed for maintaining the diversity of the B and T cells so they can be able to recognize diverse foreign agents allowing the body to fight infections. The mutations can impair RAG complex formation and function, resulting in an impaired B and T cells' function. Depending on the residual activity of the RAG proteins the disease can be more or less severe. In less severe cases symptoms are milder and may appear later in life.[1][2][3] Treatment is with bone marrow transplantation.[3]

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
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
B lymphocytopenia
Low B cell count
0010976
Combined immunodeficiency
0005387
Decreased circulating IgG level
0004315
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
T lymphocytopenia
Low T cell count
Reduced number of T cells

[ more ]

0005403

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.

References

  1. Ravin SSD, Cowen EW, Zarember KA et al. Hypomorphic Rag mutations can cause destructive midline granulomatous disease. Blood. 2010; 116:1263:1271. https://www.bloodjournal.org/content/116/8/1263.long?sso-checked=true.
  2. Notarangelo LD, Kim M-S, Walter JE & Lee YN. Human RAG mutations: biochemistry and clinical implications. Nature reviews Immunology. 2016; 16(4):234-246. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757527/.
  3. Abolhassani H, Wang N, Aghamohammadi A, et al. A Hypomorphic RAG1 Mutation Resulting in a Phenotype Resembling Common Variable Immunodeficiency. The Journal of allergy and clinical immunology. 2014; 134(6):1375-1380. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261008/.