Adenosine deaminase 2 deficiency

Adenosine Deaminase 2 Deficiency (DADA2) is a rare genetic disorder that affects multiple body systems, including the immune system and blood vessels. It is characterized by a variety of symptoms, including but not limited to, recurrent strokes, immune deficiency, and systemic inflammation. This condition is caused by mutations in the CECR1 gene, which encodes for the enzyme adenosine deaminase 2. The deficiency of this enzyme leads to an accumulation of adenosine and deoxyadenosine, which are toxic to cells, particularly those of the immune system and endothelial cells lining the blood vessels.

Symptoms and Signs

The clinical presentation of DADA2 can vary significantly among affected individuals. Common symptoms include:

• Vasculitis: Inflammation of blood vessels, which can lead to blockages or weakening of vessels, potentially causing strokes or bleeding.
• Immunodeficiency: Increased susceptibility to infections due to impaired immune system function.
• Fever: Recurrent fevers without an obvious source of infection.
• Skin Rash: Various skin lesions, often resembling those seen in patients with polyarteritis nodosa.
• Musculoskeletal Pain: Joint and muscle pains.

Genetics

DADA2 is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. The gene implicated in DADA2 is CECR1, located on chromosome 22. Mutations in this gene lead to reduced or absent activity of the adenosine deaminase 2 enzyme.

Diagnosis

Diagnosis of DADA2 involves a combination of clinical evaluation and laboratory tests, including:

• Genetic testing to identify mutations in the CECR1 gene.
• Measurement of adenosine deaminase 2 enzyme activity in the blood.
• Assessment of immune function and inflammatory markers.

Treatment

There is no cure for DADA2, but treatments are available to manage symptoms and prevent complications. Treatment strategies may include:

• Immunosuppressants to control inflammation and immune system hyperactivity.
• Antibiotics or antifungal medications to prevent or treat infections.
• Hematopoietic stem cell transplantation has been successful in some cases, offering a potential cure by correcting the genetic defect.

Prognosis

The prognosis for individuals with DADA2 varies depending on the severity of symptoms and the effectiveness of treatment. Early diagnosis and appropriate management are crucial for improving outcomes and preventing serious complications.

See Also

• Adenosine Deaminase Deficiency
• Vasculitis
• Genetic Disorders
• Immunodeficiency