Adenosine deaminase deficiency




Adenosine deaminase deficiency is an inherited condition that affects the immune system and typically leads to severe combined immunodeficiency (SCID). People with SCID have a reduced or absent immune response which leaves them vulnerable to frequent bacterial, viral, and fungal infections. Most people affected by ADA develop symptoms of the condition before 6 months of age. However, approximately 10-15% of affected people have a "delayed" onset of symptoms; diagnosis of these cases, which are often less severe, typically takes place later in childhood (often between age 1 and 10) or even into adulthood.


In most cases, signs and symptoms of adenosine deaminase deficiency (ADA) develop before 6 months of age. These affected babies are usually diagnosed with severe combined immunodeficiency (SCID), a condition characterized by a reduced or absent immune response. Babies with SCID are vulnerable to frequent bacterial, viral, and fungal infections. Although many of these infections would cause no illness or only mild disease in healthy children, they can be very severe and even life-threatening in children with SCID. Signs and symptoms of SCID include chronic diarrhea; pneumonia and other lung infections; widespread skin rashes; slowed growth; absent tonsils and lymph nodes; bone abnormalities; and/or developmental delay.

Approximately 10-15% of affected people have a "delayed" onset of symptoms, which typically develop later in childhood (often between age 1 and 10) or even into adulthood. In these cases, people are usually diagnosed with "combined immunodeficiency (CID)" since signs and symptoms are initially milder than those seen in SCID. However, the immune response becomes more damaged the longer the condition goes undiagnosed. Over time, these affected people may develop chronic lung damage, malnutrition, and other health problems.


Adenosine deaminase deficiency is caused by changes (mutations) in the ADA gene. This gene encodes an enzyme that is found in the lymphocytes (specialized white blood cells), which are an important part of the immune system and help protect the body from infections. The function of this enzyme is to convert a substance that is harmful to lymphocytes (called deoxyadenosine) to a non-toxic material. Mutations in the ADA gene cause this enzyme to have reduced or absent function, allowing deoxyadenosine to buildup in the lymphocytes. This results in the loss of lymphocytes before they are able to mature and fight infection, leading to severe combined immunodeficiency.

The enzyme adenosine deaminase is encoded by a gene on chromosome 20. ADA deficiency is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome (chromosome 20 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. Age of onset and severity is related to some 29 known genotypes associated with the disorder.

Adenosine deaminase deficiency is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.


Genetic testing is available for ADA, the gene known to cause adenosine deaminase deficiency. Carrier testing for at-risk relatives and prenatal testing are possible if the disease-causing mutations in the family are known.

In some states of the United States, newborns are screened for various conditions that can cause severe combined immunodeficiency, including adenosine deaminase deficiency (ADA). In the absence of newborn screening, ADA is typically suspected in people with frequent infections and other characteristic symptoms. The diagnosis can be confirmed by blood tests that demonstrates the following:

  • Evidence of combined immunodeficiency such as low levels of certain types of lymphocytes (white blood cells) and/or absent lymphoid tissue (i.e. thymus, tonsils, and lymph nodes)
  • Low (<1%) adenosine deaminase (the enzyme encoded by the ADA gene) activity

Other tests that are helpful in establishing a diagnosis include x-rays that show ADA-associated bone abnormalities and genetic testing that identifies a change (mutation) in each copy of the ADA gene.


The long-term outlook (prognosis) for people with adenosine deaminase deficiency (ADA) varies depending on the severity of the condition, the timing of the diagnosis and the response to treatment. For example, without early diagnosis and treatment, babies with ADA usually do not survive past age 2. However, if bone marrow transplant/stem cell transplant (transplantation of blood-forming stem cells from the bone marrow of a healthy person) is effective, the prognosis is typically good.


The treatment of adenosine deaminase deficiency usually consists of the following:

  • Early diagnosis and therapy for bacterial, viral, and fungal infections
  • Prophylactic medications for certain types of pneumonia
  • Intravenous (IV) immunoglobulin to boost the body's natural response to infections

It is also important to restore the function of the immune system, if possible. The most effective treatment is transplantation of blood-forming stem cells from the bone marrow of a healthy person (called bone marrow transplant/stem cell transplant or BMT/SCT). This therapy cures the condition in approximately 70% or more of people with severe combined immunodeficiency (SCID), including those affected by ADA. 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 synthetic form of the enzyme.

Other Treatments include:

  • Bone marrow transplant
  • Gene therapy
  • ADA enzyme in PEG vehicle 

On September 14, 1990, the first gene therapy to combat this disease was performed by Dr. William French Anderson on a four-year-old girl, Ashanti DeSilva, at theNational Institutes of Health, Bethesda, Maryland, U.S.A.

See also : Strimvelis, a stem cell therapy nearing EU approval in 2016.

The European Medicines Agency (EMA) endorsed a therapy, called Strimvelis, for a tiny number of children with ADA Severe Combined Immune Deficiency (ADA-SCID) for whom no matching bone marrow donor is available on Friday, April 1, 2016.


  • NIH