It accounts for about 10–20% of all cases of autosomal recessive forms of severe combined immunodeficiency (SCID) after excluding disorders related to inbreeding.

The main symptoms of ADA deficiency include pneumonia, chronic diarrhea, widespread skin rashes, jaundice (from hepatic infections), and candidiasis of the mouth and esophagus.

[citation needed] Diagnosis in developed nations is usually done through standardized newborn screening tests for a range of congenital diseases, including ADA deficiency.

Most newborns with SCID, including those with ADA deficiency as an underlying cause, can be identified before the onset of major infections due to their decreased levels of T-cell receptor excision circles (TRECs).

[4] In the absence of newborn screening or to differentiate from other causes of SCID, some (but not all) children will display one or more of these features which are sometimes seen in ADA deficiency but not other forms of SCID:[4] When ADA deficiency is suspected, the diagnosis may be confirmed through several lab tests of the patient's red blood cells, or via genetic testing.

Due to the frequency it is encountered and its indifference to most antibiotics, clinicians must be careful to include a medication that can prevent Pneumocystis pneumonia.

[12] Long-term definitive treatment of ADA deficiency is typically achieved by transplantation of hematopoietic stem cells from a matched family member donor, preferably a sibling.

[11] In September 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 the National Institutes of Health, Bethesda, Maryland, U.S.A.[13] In April 2016 the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed and recommended for approval a stem cell gene therapy called Strimvelis, for children with ADA-SCID for whom no matching bone marrow donor is available.