Deficiency of Adenosine Deaminase 2 (DADA2)

Abstract

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease resulting from mutations in ADA2 (formerly named CECR1). Initially described by two groups in 2014, additional reports have documented that the phenotypic expression is quite broad. Although commonly presenting in childhood, patients can present throughout their lives with varying forms of inflammatory, neurologic, hematologic, and immunologic phenotypes. Frequently reported disease manifestations include lacunar strokes, non-cirrhotic portal hypertension, immunodeficiencies, and bone marrow involvement that can include an overt pancytopenia ranging to cell-specific immune destruction. The role of adenosine deaminase 2 (ADA2) remains incompletely understood. The lack of ADA2 in patients with DADA2 results in endothelial cell fragility and a skewing of macrophage development toward the inflammatory, M1 macrophage. Current treatment options are tailored toward the individual clinical presentations but the utilization of anti-tumor necrosis factor (TNF) medications has been highly effective at reducing the risk for stroke. Hematopoietic stem cell transplant offers a potential cure for the disease.