About Adenosine Deaminase (ADA) Deficiency

What Is Adenosine Deaminase (ADA) Deficiency?

Adenosine deaminase [uh-DEN-uh-seen dee-AM-ih-nayz] deficiency, also called ADA deficiency, is a rare genetic disorder that affects the immune system. It happens when the body does not make enough of an enzyme called adenosine deaminase. This enzyme helps break down substances made during normal cell activity. Without enough ADA, these substances can build up and damage lymphocytes, a type of white blood cell that helps the body fight infections. As a result, people with ADA deficiency may have a weakened immune system and a higher risk of serious or repeated infections.

ADA deficiency is different from adenosine deaminase 2 deficiency, also called ADA2 deficiency or DADA2. ADA deficiency is caused by changes in the ADA gene and mainly affects immune cell development and infection risk. ADA2 deficiency is caused by changes in the ADA2 gene and more often causes inflammation in blood vessels or other tissues. This can lead to symptoms such as fevers, skin changes, strokes, low blood cell counts, or immune problems. Because the names sound similar, a healthcare professional can explain which condition a person has and what testing or treatment may be needed.

What Causes Adenosine Deaminase Deficiency?

ADA deficiency is caused by changes, also called variants, in the ADA gene. This gene gives the body instructions for making the adenosine deaminase enzyme. ADA is found throughout the body, but it is especially important in lymphocytes, a type of white blood cell that helps protect the body from infections.

When ADA enzyme activity is very low, certain substances can build up inside cells. These substances are especially harmful to lymphocytes. When lymphocytes are damaged or do not develop normally, the immune system cannot fight infections as well as it should.

ADA deficiency is a genetic disorder in an autosomal recessive pattern. This means a person usually has ADA deficiency only if they inherit one changed ADA gene from each parent. Parents who carry one changed ADA gene typically do not have symptoms. ADA deficiency is not caused by lifestyle choices or anything a parent did or did not do during pregnancy.

Symptoms of ADA Deficiency

Many babies with severe ADA deficiency, also called ADA-SCID, develop symptoms in the first few months of life. Symptoms can vary, but early signs may include:

Frequent or serious infections, such as pneumonia
Long-lasting diarrhea
Skin rashes
Poor growth or trouble gaining weight
Developmental delays in some children

Some people have a milder or later-onset form of ADA deficiency. Symptoms may appear later in childhood or, rarely, adulthood. These symptoms may include:

Repeated sinus, ear, or lung infections
Chronic cough or breathing problems
Lung damage from repeated infections
Poor weight gain, fatigue, or other health problems related to ongoing infections

ADA deficiency should not be confused with ADA2 deficiency, also called DADA2. ADA2 deficiency is a separate genetic condition that more often causes inflammation in blood vessels and other tissues.

How Is ADA Deficiency Diagnosed?

ADA deficiency may be found through newborn screening, blood tests, enzyme testing, or genetic testing. A healthcare provider may recommend one or more of the following tests:

Family and medical history: A healthcare provider asks about symptoms, infections, and any family history of immune system conditions.
Blood tests: Blood tests can check the number and types of immune cells, including lymphocytes.
ADA enzyme activity test: This test measures how well the ADA enzyme is working.
Genetic testing: Genetic testing can look for changes in the ADA gene and help confirm the diagnosis.
Newborn screening: In places where screening is available, a small blood sample collected shortly after birth may show signs of severe immune deficiency, including ADA-SCID.
Prenatal testing: If a family is known to be at risk, testing during pregnancy may be available through procedures such as chorionic villus sampling or amniocentesis.

Early diagnosis is important because treatment started soon after diagnosis can help lower the risk of serious infections and improve outcomes. The right testing plan depends on a person’s symptoms, age, family history, and the healthcare provider’s recommendations.

Treatment Options for ADA Deficiency

Treatment for ADA deficiency depends on the person’s age, symptoms, overall health, and whether a suitable stem cell donor is available. The main goals of treatment are to:

Help the immune system work better
Prevent or treat serious infections
Reduce the buildup of harmful substances caused by low ADA enzyme activity
Support healthy growth and development
Improve long-term health and quality of life

Treatment options may include:

Enzyme replacement therapy: This treatment gives the body a form of the ADA enzyme it is missing. It can help improve immune function and may be used while a person is waiting for another treatment or when other treatments are not possible. It usually needs to be given regularly over time.
Hematopoietic stem cell transplant, also called a bone marrow or stem cell transplant: This treatment replaces the person’s blood-forming stem cells with healthy donor stem cells. These new cells can make working immune cells. A transplant from a well-matched related donor is often preferred when available.
Gene therapy: Gene therapy uses a person’s own stem cells. The cells are collected, corrected in a lab so they can make ADA enzyme, and then returned to the body. This may be an option for some people with ADA-SCID, depending on availability, eligibility, and local approvals.

Supportive care is also important. This may include prompt treatment of infections, medicines to prevent certain infections, immunoglobulin replacement in some cases, and avoiding live vaccines until an immune specialist says they are safe.

The best treatment plan is different for each person. Families should discuss the benefits, risks, timing, and availability of each option with a healthcare team experienced in treating ADA deficiency or ADA-SCID.