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Disease Profile

Adenosine deaminase deficiency

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 / 1 000 000

US Estimated

Europe Estimated

Age of onset






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


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.


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.


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


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.


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.


Not applicable


Other names (AKA)

ADA deficiency; Severe combined immunodeficiency due to adenosine deaminase deficiency; Severe combined immunodeficiency due to ADA deficiency;


Congenital and Genetic Diseases; Immune System Diseases; Metabolic disorders


Adenosine deaminase deficiency (ADA deficiency) is an inherited condition that damages the immune system and is a common cause of severe combined immunodeficiency (SCID). People with SCID due to ADA deficiency are unable to fight off most types of infections, including bacterial, viral and fungal infections. Most people with ADA deficiency develop symptoms before 6 months of age. The earliest symptoms of ADA deficiency include pneumonia, chronic diarrhea, widespread skin rashes, slowed growth, and/or developmental delay. Some people with ADA deficiency will develop symptoms later in life. The symptoms in the late-onset form are typically milder than in the form that occurs in infancy. ADA deficiency is caused by mutations in the ADA gene and is inherited in an autosomal recessive manner.[1][2] Diagnosis may be suspected by newborn screening or symptoms and confirmed by blood and genetic test results. Currently, the most effective treatment is transplantation of blood-forming stem cells from the bone marrow of a healthy brother or sister of the person with ADA deficiency.[2][3]


The symptoms of adenosine deaminase deficiency (ADA deficiency) usually begin before 6 months of age.[1][2] Babies with ADA deficiency usually develop serious lung infections and chronic diarrhea. They have trouble gaining weight and do not grow very well. Other symptoms include skin rashes, absent tonsils and lymph nodes, bone abnormalities, and developmental delay.[2][4] Approximately 10-15% of people with ADA deficiency do not develop symptoms until later in childhood, often between ages 1 and 10, or even into adulthood. In these cases, people are usually diagnosed with "combined immunodeficiency (CID)", since symptoms are initially milder than those seen in SCID. However, over time, people with the milder form of ADA deficiency may develop chronic lung damage, malnutrition, and other health problems.[1][2]

There are some people who have partial ADA deficiency. People with this condition have low amount of ADA enzyme in some cells, but have normal immune systems. Partial ADA deficiency is considered a benign condition that does not cause health problems.[2]

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:
30%-79% of people have these symptoms
Absence of lymph node germinal center
Absent tonsils
Anti-thyroid peroxidase antibody positivity
B lymphocytopenia
Low B cell count
Watery stool
Failure to thrive
Faltering weight
Weight faltering

[ more ]

Increased circulating IgE level
Inflammatory abnormality of the skin
Skin inflammation
Lack of T cell function
Pulmonary insufficiency
Recurrent opportunistic infections
Recurrent otitis media
Recurrent middle ear infection
Recurrent pneumonia
Recurrent upper respiratory tract infections
Recurrent colds
Sinus inflammation
T lymphocytopenia
Low T cell count
Reduced number of T cells

[ more ]

Percent of people who have these symptoms is not available through HPO
Abnormality of pelvic girdle bone morphology
Abnormal shape of pelvic girdle bone
Absent specific antibody response
Anterior rib cupping
Aplasia of the thymus
Absent thymus
Autoimmune hemolytic anemia
Autoimmune thrombocytopenia
Autosomal recessive inheritance
B-cell lymphoma
Decreased circulating IgA level
Decreased circulating IgG2 level
Decreased circulating total IgM
Diffuse mesangial sclerosis
High blood eosinophil count
Growth arrest lines
Enlarged liver
Flattened vertebrae
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections

[ more ]

Recurrent fungal infections
Recurrent viral infections
Reduced red cell adenosine deaminase level
Severe B lymphocytopenia
Severe combined immunodeficiency
Somatic mosaicism
Increased spleen size


Adenosine deaminase deficiency (ADA deficiency) is caused by changes (mutations) in the ADA gene. This gene is responsible for making an enzyme that is found in specialized white blood cells (lymphocytes). Lymphocytes are an important part of the immune system and help protect the body from infections. The function of the ADA enzyme is to convert a substance that is harmful to lymphocytes (called deoxyadenosine) to a non-harmful substance. Mutations in the ADA gene lead to a non-working or poorly working ADA enzyme. This causes deoxyadenosine to buildup in the lymphocytes. Because of this build up, lymphocytes are unable to grow and fight infection, leading to severe combined immunodeficiency.[1][2][4]


Most states in the United States screen newborns for severe combined immune deficiency (SCID).[2][4] One common cause of SCID is adenosine deaminase deficiency (ADA deficiency). If a newborn screen result is abnormal for SCID, additional blood tests are necessary to confirm the diagnosis of ADA deficiency (and other less common causes for SCID). These blood tests include testing for levels of immunoglobulins and white blood cells (WBCs) including T cells, B cells and natural killer cells.[2][4] Immunoglobulins and WBCs are important parts of the body’s immune system. Genetic testing to identify mutations in the ADA gene may be used to confirm the diagnosis.[2]

In children and adults with the mild form of ADA deficiency, the diagnosis is made based on symptoms which include frequent unusual infections, low WBCs in the blood, absent tonsils or lymph nodes, and low levels of the adenosine deaminase enzyme. Genetic testing for mutations in the ADA gene can confirm the diagnosis of the mild form of ADA deficiency.[2][4]

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.

    Newborn Screening

    • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
    • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
    • US National Newborn Screening Status Report (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.
    • The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.


      The treatment of severe combined immune deficiency due to adenosine deaminase deficiency (ADA deficiency) may include the following:[3][5]

      Early diagnosis and treatment of bacterial, viral, and fungal infections
      Preventative medications for certain types of pneumonia
      Intravenous (IV) immunoglobulin to boost the body's natural response to infections
      Bone marrow or stem cell transplant
      Gene therapy

      The primary treatment is transplantation of blood-forming stem cells from the bone marrow of a healthy brother or sister (allogenic bone marrow transplant /stem cell transplant or BMT/SCT). This therapy is effective in approximately 70% or more of people with severe combined immunodeficiency (SCID), including SCID caused by ADA deficiency.[5] 

      If a BMT/SCT is not an option, enzyme replacement therapy (ERT) may be recommended. ERT is a treatment that replaces the enzyme that is missing or not working properly (adenosine deaminase) with a bovine form of the enzyme that has been genetically modified to work in humans.[3][5][6]

      Gene therapy is also available through clinical trials, and appears to be successful in treating people with SCID due to ADA deficiency. Gene therapy involves replacing a copy of the non-working ADA gene with a working copy, so that a person can make the ADA enzyme on his or her own. Gene therapy for SCID due to ADA deficiency has been approved in Europe [7], but is still considered experimental in the US.

      FDA-Approved Treatments

      The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

      • Pegademase bovine(Brand name: Adagen) Manufactured by Lediant Biosciences
        FDA-approved indication: March 1990, pegademase bovine (Adagen) was approved for enzyme replacement therapy for ADA deficiency in patients with severe combined immunodeficiency.
        National Library of Medicine Drug Information Portal
      • Elapegademase-lvlr(Brand name: Revcovi) Manufactured by Leadiant Biosciences, Inc.
        FDA-approved indication: October 2018, elapegademase-lvlr (Revcovi) was approved for the treatment of Adenosine Deaminase-Severe Combined Immunodeficiency (ADA-SCID).


      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

        Organizations Providing General Support

          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

          • The American Society of Gene & Cell Therapy provides information on the treatment of immunodeficiency diseases.
          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • Genetics Home Reference (GHR) contains information on Adenosine deaminase 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.
          • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • 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.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Adenosine deaminase deficiency. Click on the link to view a sample search on this topic.


              1. Adenosine deaminase deficiency. Genetics Home Reference. July 2013; https://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency.
              2. Hershfield M. Adenosine Deaminase Deficiency. GeneReviews. Mar 2017; https://www.ncbi.nlm.nih.gov/books/NBK1483.
              3. Kohn DB, Hershfield MS, Puck JM, Aiuti A et al. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol. Sept 2018; available on-line. https://www.ncbi.nlm.nih.gov/pubmed/30194989.
              4. Rubinstein A. Adenosine deaminase deficiency: Pathogenesis, clinical manifestations, and diagnosis. UpToDate. Nov 2016; https://www.uptodate.com/contents/adenosine-deaminase-deficiency-pathogenesis-clinical-manifestations-and-diagnosis.
              5. Rubinstein A. Adenosine deaminase deficiency: Treatment. UpToDate. August 2017; https://www.uptodate.com/contents/adenosine-deaminase-deficiency-treatment.
              6. Scott O, Kim VH-D, Reid B, Pham-Huy A, Atkinson A, Aiuti A, Grunebaum E. Long-term outcome of Adenosine deaminase-deficient patients – a single-center experience. J Clin Immunol. 2017; 37:582-591. https://www.ncbi.nlm.nih.gov/pubmed/28748310.
              7. Aiuti A, Roncarolo MG, Naldini L. Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products. EMBO Molecular Med. 2017; 9(6):737-740. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452047.

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