adenosine deaminase 2 deficiency

Adenosine deaminase 2 (ADA2) deficiency is a disorder characterized by abnormal inflammation of various tissues, particularly the blood vessels (vasculitis). Signs and symptoms can begin anytime from early childhood to adulthood. The severity of the disorder also varies, even among affected individuals in the same family.

Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, the uncontrolled inflammation that occurs in ADA2 deficiency can damage many of the body's tissues and organs, including the skin, gastrointestinal system, kidneys, and nervous system. Depending on the severity and location of the inflammation, the disorder can cause disability or be life-threatening. Features that have been described in people with ADA2 deficiency include fevers that are intermittent, meaning they come and go; areas of net-like, mottled skin discoloration called livedo racemosa; an enlarged liver and spleen (hepatosplenomegaly); and recurrent strokes affecting structures deep in the brain that can start in the first few years of life. ADA2 deficiency causes mild immune system abnormalities in some individuals, but it is usually not associated with a significantly increased risk of bacterial and viral infections.

ADA2 deficiency is sometimes described as a form of polyarteritis nodosa (PAN), a disorder that causes inflammation of blood vessels throughout the body (systemic vasculitis). However, not all researchers classify ADA2 deficiency as a type of PAN.

Only a few dozen individuals with ADA2 deficiency have been described in the medical literature. However, researchers suspect that it may not be a rare disease. They are working to determine whether ADA2 deficiency could underlie other, more common forms of vasculitis and stroke whose causes are currently unknown.

ADA2 deficiency is caused by mutations in the CECR1 gene. This gene provides instructions for making an enzyme called adenosine deaminase 2. Studies suggest that this enzyme plays an essential role in keeping the lining of blood vessel walls intact. It also appears to be involved in the growth and development of certain immune system cells, including macrophages, which are a type of white blood cell that plays a critical role in inflammation. Some macrophages are pro-inflammatory, meaning they promote inflammation, while others are anti-inflammatory, meaning they reduce inflammation.

Mutations in the CECR1 gene severely reduce or eliminate the function of adenosine deaminase 2. Researchers do not fully understand how a loss of this enzyme's function leads to the features of ADA2 deficiency. They speculate that a lack of this enzyme may disrupt the balance between pro-inflammatory and anti-inflammatory macrophages in various tissues, leading to abnormal inflammation. The enzyme's role in maintaining the structural integrity of blood vessels could help explain why the blood vessels are most often affected by inflammation in this disorder.

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

These resources address the diagnosis or management of adenosine deaminase 2 deficiency:

These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:

  • ADA2 deficiency
  • childhood-onset polyarteritis nodosa
  • DADA2
  • deficiency of ADA2
  • Sneddon syndrome