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Adenosine deaminase deficiency

Reviewed February 2008

What is adenosine deaminase deficiency?

Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. Infants with SCID typically experience pneumonia, chronic diarrhea, and widespread skin rashes, and grow much more slowly than healthy children. Some also have neurological problems such as developmental delay, movement disorders, and hearing loss. If not treated in a way that restores immune function, children with SCID usually live only a year or two.

Most individuals with adenosine deaminase deficiency are diagnosed with SCID in the first 6 months of life. In about 10 percent to 15 percent of cases, onset of immune deficiency is delayed to between 6 and 24 months of age (delayed onset) or even until adulthood (late onset). Immune deficiency in these later-onset cases tends to be less severe, causing primarily recurrent upper respiratory and ear infections. Over time, affected individuals may develop chronic lung damage, allergies, and other health problems.

How common is adenosine deaminase deficiency?

Adenosine deaminase deficiency is very rare and is estimated to occur in approximately 1 in 200,000 to 1,000,000 newborns worldwide. This disorder is responsible for approximately 15 percent of SCID cases.

What genes are related to adenosine deaminase deficiency?

The ADA gene provides instructions for producing the enzyme adenosine deaminase. This enzyme is found throughout the body but is most active in lymphocytes, the specialized white blood cells that protect the body against potentially harmful invaders by making antibodies or by directly attacking virus-infected cells. Lymphocytes are produced in specialized lymphoid tissues including the thymus, which is a gland located behind the breastbone, and lymph nodes, which are found throughout the body. Together, lymphocytes in the blood and in lymphoid tissues make up the immune system.

The function of the adenosine deaminase enzyme is to eliminate a molecule called deoxyadenosine, which is generated when DNA is broken down. Adenosine deaminase converts deoxyadenosine, which is toxic to lymphocytes, to another molecule called deoxynosine that is not harmful. Mutations in the ADA gene reduce or eliminate the activity of adenosine deaminase and allow the buildup of deoxyadenosine to levels that are toxic to lymphocytes.

Immature lymphocytes in the thymus are particularly vulnerable to a toxic buildup of deoxyadenosine. The number of lymphocytes in other lymphoid tissues is also greatly reduced, resulting in the signs and symptoms of SCID.

How do people inherit adenosine deaminase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about treatment for adenosine deaminase deficiency?

You may find information on treatment or management of adenosine deaminase deficiency or some of its symptoms in the links below, particularly the links for Gene Reviews, Educational resources, and Patient support.

Where can I find additional information about adenosine deaminase deficiency?

You may find the following resources about adenosine deaminase deficiency helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Health Topic: Immune System and Disorders (http://www.nlm.nih.gov/medlineplus/immunesystemanddisorders.html)
    • Health Topic: Metabolic Disorders (http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html)
  • Additional NIH Resources - National Institutes of Health
    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.153)
    • National Human Genome Research Institute: Learning About Severe Combined Immunodeficiency (http://genome.gov/13014325)
    • National Institute of Child Health and Human Development: Primary Immunodeficiency: When the Body's Defenses are Missing (http://www.nichd.nih.gov/publications/pubs/primary_immuno.cfm)
  • Educational resources - Information pages
    • KidsHealth (http://kidshealth.org/parent/medical/allergies/severe_immunodeficiency.html)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,69/)
    • Merck Manual (http://www.merck.com/mmhe/sec16/ch184/ch184i.html)
    • National Marrow Donor Program (http://www.marrow.org/PATIENT/Undrstnd_Disease_Treat/Lrn_about_Disease/Immune_System/SCID_and_Tx/)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=277)
    • University of Utah Genetic Science Learning Center (http://learn.genetics.utah.edu/content/disorders/whataregd/ada/index.html)
  • Patient support - For patients and families
    • Children Living with Inherited Metabolic Diseases (http://www.climb.org.uk/)
    • Immune Deficiency Foundation (http://www.primaryimmune.org/)
    • Jeffrey Modell Foundation (http://www.info4pi.org/)
    • National Organization for Rare Disorders (http://rarediseases.org/search/rdbdetail_abstract.html?disname=Severe+Combined+Immunodeficiency)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ada)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=25480)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22Severe+Combined+Immunodeficiency%22+OR+%22adenosine+deaminase+deficiency%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Severe+Combined+Immunodeficiency[MAJR])+AND+((adenosine+deaminase+deficiency[TIAB])+OR+(ada-scid[TIAB])+OR+(adenosine+deaminase+deficient+severe+combined+immunodeficiency[TIAB])+OR+(ada+deficiency[TIAB]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1800+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Immunodeficiency Diseases Caused by Adenosine Deaminase Deficiency and Purine Nucleoside Phosphorylase Deficiency (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=109)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=102700)

What other names do people use for adenosine deaminase deficiency?

  • ADA deficiency
  • ADA-SCID
  • adenosine deaminase deficient severe combined immunodeficiency
  • SCID due to ADA deficiency
  • severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about adenosine deaminase deficiency?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding adenosine deaminase deficiency?

antibody ; autosomal ; autosomal recessive ; bacteria ; cell ; chronic ; deficiency ; developmental delay ; DNA ; enzyme ; fungus ; gene ; immune system ; immunodeficiency ; infection ; lymph ; lymph node ; lymphocyte ; lymphoid ; molecule ; mutation ; neurological ; NK cells ; pneumonia ; recessive ; respiratory ; sign ; symptom ; thymus ; tissue ; toxic ; virus ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol. 2004;22:625-55. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15032591)
  • Hershfield MS. Genotype is an important determinant of phenotype in adenosine deaminase deficiency. Curr Opin Immunol. 2003 Oct;15(5):571-7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14499267)
  • Hershfield MS. New insights into adenosine-receptor-mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency. Eur J Immunol. 2005 Jan;35(1):25-30. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15580654)
  • Nofech-Mozes Y, Blaser SI, Kobayashi J, Grunebaum E, Roifman CM. Neurologic abnormalities in patients with adenosine deaminase deficiency. Pediatr Neurol. 2007 Sep;37(3):218-21. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17765813)
  • Nyhan WL. Disorders of purine and pyrimidine metabolism. Mol Genet Metab. 2005 Sep-Oct;86(1-2):25-33. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16176880)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2008
Published: January 23, 2009