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Adenosine deaminase 2 deficiency
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Adenosine deaminase 2 deficiency

Adenosine deaminase 2 (ADA2) deficiency is an autoinflammatory disorder characterized by abnormal inflammation of tissues, particularly blood vessels, which can lead to vasculitis and stroke.

Overview

ADA2 deficiency causes the immune system to trigger abnormal, unprovoked inflammation. This inflammation can damage various organs and tissues, most notably the blood vessels, a condition known as vasculitis. The disorder can manifest anytime from early childhood to adulthood.

Symptoms

  • Vasculitis: Inflammation of blood vessels throughout the body.
  • Skin: Mottled, net-like skin discoloration known as livedo racemosa.
  • Systemic signs: Intermittent fevers and an enlarged liver and spleen (hepatosplenomegaly).
  • Neurological: Recurrent strokes, which may begin in early childhood.
  • Immune system: Additional abnormalities that may increase susceptibility to bacterial and viral infections.

Causes & Risk Factors

The condition is caused by mutations in the ADA2 gene, which provides instructions for the adenosine deaminase 2 enzyme. This enzyme is critical for the development and function of macrophages—white blood cells that regulate inflammation. A deficiency in this enzyme is thought to disrupt the balance between pro-inflammatory and anti-inflammatory macrophages, leading to chronic, abnormal inflammation.

Inheritance

ADA2 deficiency is inherited in an autosomal recessive pattern. Both copies of the gene in each cell must have mutations for the condition to occur. Parents of an affected individual are typically carriers who do not exhibit symptoms of the disorder.

Frequently Asked Questions

First‑line management includes supportive care and treatment of infections. For inflammatory manifestations, tumor necrosis factor‑α (TNF‑α) inhibitors (e.g., etanercept, adalimumab) have the strongest evidence for reducing vasculitis activity and preventing strokes. Initiate TNF‑α blockade as soon as the diagnosis is confirmed or when patients have recurrent ischemic events, severe livedo, or systemic inflammation despite conventional therapy. In refractory cases, hematopoietic stem‑cell transplantation may be considered.
ll first‑degree relatives should undergo targeted sequencing or deletion/duplication analysis for the ADA2 gene to identify carriers or affected individuals. Since the disorder is autosomal recessive, carrier parents have a 25 % chance of having another affected child with each pregnancy. Carrier testing enables informed reproductive choices, including preimplantation genetic diagnosis (PGD) or prenatal testing via chorionic villus sampling/amniocentesis.
DA2 deficiency often presents with livedo racemosa (net‑like skin discoloration), recurrent strokes or transient ischemic attacks, hepatosplenomegaly, and a family history of early‑onset stroke or autoinflammatory symptoms. Laboratory tests typically show normal acute‑phase reactants between flares and may reveal low ADA2 enzyme activity. Genetic testing for biallelic ADA2 mutations confirms the diagnosis, whereas Kawasaki disease has mucocutaneous changes and coronary artery involvement, and PAN shows necrotizing arteritis without the characteristic skin pattern.
Baseline brain MRI/MRA should be obtained at diagnosis, followed by repeat imaging every 6–12 months or after any new neurologic symptom. Antiplatelet therapy (low‑dose aspirin) is often used unless contraindicated. Aggressive control of hypertension, avoidance of smoking exposure, and prompt treatment of infections are also important. Early initiation of TNF‑α inhibitors has been shown to lower the incidence of new strokes.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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