Can ADA deficiency be inherited, and what is the risk for future children?

DA deficiency follows an autosomal recessive inheritance pattern. If both parents carry a defective ADA gene, each pregnancy has a 25 % chance of producing an affected child, a 50 % chance of a carrier, and a 25 % chance of a normal child. Genetic counseling and carrier testing for both parents are recommended before conception.===

How can a family prepare for an ADA deficiency genetic test?

sk the ordering clinician for a detailed consent form that explains the purpose of the test, potential results, and implications for family members. Bring a list of all family medical histories, especially any cases of immune deficiency or early childhood infections. The test is usually done via a blood draw or a cheek swab; no special fasting or medication changes are required.

What are the earliest warning signs that a newborn might have ADA deficiency?

In the first weeks of life, infants may develop persistent, severe infections such as pneumonia or thrush, chronic diarrhea, or skin rashes that do not respond to standard treatments. They may also show poor weight gain and delayed developmental milestones. If these symptoms appear, a pediatrician should order a lymphocyte count and consider a flow cytometry test for T‑cell function.

What treatment options are available for children with ADA‑SCID, and how do they differ?

The main treatments are enzyme replacement therapy (ERT) with pegademase bovine, hematopoietic stem cell transplantation (HSCT), and gene therapy using lentiviral vectors. ERT can provide temporary immune support but requires lifelong infusions. HSCT offers a potential cure but carries risks of graft-versus-host disease and requires a matched donor. Gene therapy is emerging as a less invasive option that corrects the ADA gene in the patient’s own cells, but it is still under clinical investigation and may not be available in all centers.

Adenosine deaminase deficiency

Adenosine deaminase (ADA) deficiency is a rare genetic disorder that severely impairs the immune system, leading to life-threatening infections and developmental issues, particularly in its most severe form, ADA-SCID.

Overview

Adenosine deaminase (ADA) deficiency is a disorder that affects the immune system. Specifically, ADA deficiency impairs the development and function of immune cells called lymphocytes. Lymphocytes are white blood cells that help the body fight infections. As a result, people with ADA deficiency often develop pneumonia, chronic diarrhea, and widespread skin rashes. Additional signs and symptoms of ADA deficiency include slow growth and developmental delays.

About 80 percent of individuals with ADA deficiency also have severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be 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. People with ADA deficiency with SCID (ADA-SCID) typically develop health problems within the first 6 months of life. Without treatment, these babies usually do not survive past age 2.

About 15 to 20 percent of people with ADA deficiency develop health problems that begin between 1 and 10 years of age (delayed onset) or in adulthood (late onset). In people with this form of ADA deficiency (known as delayed or late-onset combined immunodeficiency or ADA-CID), the immune deficiency tends to be less severe than in people with ADA-SCID. People with ADA-CID typically have recurrent upper respiratory and ear infections. Over time, affected individuals may develop chronic lung damage, malnutrition, and other health problems.

In some individuals, ADA deficiency only impacts red blood cells. Since white blood cells are not affected, these individuals have normal immune systems. This form of the condition is known as partial ADA deficiency. Individuals with this form do not have any health problems related to the condition. They often only find out they have ADA deficiency when they undergo testing because of an affected relative or during a normal health screening.

Frequency

Adenosine deaminase deficiency is very rare. It is estimated to occur in approximately 1 in 500,000 newborns worldwide. Approximately 15 percent of people with SCID have ADA deficiency.

Causes

Adenosine deaminase deficiency is caused by variants (also called mutations) in the ADA gene. This gene provides instructions for producing the enzyme adenosine deaminase. This enzyme is found throughout the body but is most active in lymphocytes. These cells protect the body against foreign invaders, such as bacteria and viruses. Lymphocytes are produced in specialized lymphoid tissues throughout the body, including in a gland located behind the breastbone called the thymus and in the lymph nodes.

The adenosine deaminase enzyme works to get rid of a molecule called deoxyadenosine, which is generated when DNA is broken down. A buildup of deoxyadenosine in cells can lead to early cell death. Adenosine deaminase converts deoxyadenosine to another molecule called deoxyinosine, which is not harmful. Variants in the ADA gene reduce or eliminate the activity of adenosine deaminase and allow deoxyadenosine to build up in cells. The severity of ADA deficiency generally depends on how much working enzyme is available. Individuals with ADA-SCID have no enzyme activity. Those with ADA-CID have greatly reduced enzyme activity, and people with partial ADA deficiency have somewhat reduced enzyme activity.

Immature lymphocytes in the thymus are particularly vulnerable to a toxic buildup of deoxyadenosine. These cells die before they can mature and help fight infection. The number of lymphocytes in other lymphoid tissues is also greatly reduced. The loss of infection-fighting cells results in the signs and symptoms of ADA deficiency.

Associated Gene

Inheritance

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

Other Names

ADA deficiency
ADA-Related Immune Deficiency, Adenosine Deaminase 1 Deficiency
ADA-SCID
ADA1 Deficiency
Adenosine deaminase deficient severe combined immunodeficiency
SCID due to ADA deficiency
Severe combined immunodeficiency due to ADA deficiency
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Additional Information & Resources

Genetic Testing Information

Genetic Testing Registry: Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Genetic and Rare Diseases Information Center

Severe combined immunodeficiency due to adenosine deaminase deficiency

Patient Support and Advocacy Resources

National Organization for Rare Disorders (NORD)

Clinical Trials

ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY

Scientific Articles on PubMed

PubMed

References

Blackburn MR, Thompson LF. Adenosine deaminase deficiency: unanticipated benefits from the study of a rare immunodeficiency. J Immunol. 2012 Feb 1;188(3):933-5. doi: 10.4049/jimmunol.1103519. No abstract available.
Dabrowska-Leonik N, Piatosa B, Slominska E, Bohynikova N, Bernat-Sitarz K, Bernatowska E, Wolska-Kusnierz B, Kalwak K, Koltan S, Dabrowska A, Gozdzik J, Ussowicz M, Pac M. National experience with adenosine deaminase deficiency related SCID in Polish children. Front Immunol. 2023 Jan 6;13:1058623. doi: 10.3389/fimmu.2022.1058623. eCollection 2022.
Grunebaum E, Booth C, Cuvelier GDE, Loves R, Aiuti A, Kohn DB. Updated Management Guidelines for Adenosine Deaminase Deficiency. J Allergy Clin Immunol Pract. 2023 Jun;11(6):1665-1675. doi: 10.1016/j.jaip.2023.01.032. Epub 2023 Feb 1.
Hershfield M, Tarrant T. Adenosine Deaminase Deficiency. 2006 Oct 3 [updated 2025 Dec 4]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026.
Hershfield MS. Genotype is an important determinant of phenotype in adenosine deaminase deficiency. Curr Opin Immunol. 2003 Oct;15(5):571-7. doi: 10.1016/s0952-7915(03)00104-3.
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. doi: 10.1002/eji.200425738.
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. doi: 10.1016/j.pediatrneurol.2007.03.011.
Nyhan WL. Disorders of purine and pyrimidine metabolism. Mol Genet Metab. 2005 Sep-Oct;86(1-2):25-33. doi: 10.1016/j.ymgme.2005.07.027.

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