Adenosine deaminase 2 deficiency

Adenosine deaminase 2 (ADA2) deficiency is a disorder characterized by abnormal inflammation of various tissues. Signs and symptoms can begin anytime from early childhood to adulthood, and severity varies even among affected members of the same family. The inflammation is unprovoked and can damage the body's tissues and organs, particularly blood vessels, where inflammation is known as vasculitis; the skin, gastrointestinal system, liver, kidneys and nervous system can also be affected. Depending on the severity and location of the inflammation, the disorder can cause disability or be life-threatening. Signs include fevers that come and go, net-like mottled skin discoloration called livedo racemosa, an enlarged liver and spleen, and recurrent strokes affecting structures deep in the brain that can start in the first few years of life, and some people have additional immune system abnormalities that raise the risk of bacterial and viral infections. The condition is sometimes described as a form of polyarteritis nodosa, a systemic vasculitis, although not all researchers classify it that way. It is caused by mutations in the ADA2 gene, which makes the enzyme adenosine deaminase 2; the enzyme plays an essential role in the growth and development of certain immune cells including macrophages, and researchers speculate that its loss upsets the balance between pro-inflammatory and anti-inflammatory macrophages. It is inherited in an autosomal recessive pattern. More than 160 individuals have been described in the medical literature, but many more may be affected and researchers are examining whether it underlies other forms of vasculitis and stroke of unknown cause. Other names include DADA2, childhood-onset polyarteritis nodosa and Sneddon syndrome.