Deficiency of adenosine deaminase 2 (DADA2): Review

Abstract

The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease caused by loss-of-function (LOF) mutations in the ADA2 gene and was first described in 2014. Initially, it was described as vasculopathy/vasculitis that mostly affected infants and young children and closely resembled polyarteritis nodosa (PAN). Skin rash and ischemic/hemorrhagic stroke are predominant symptoms. However, the clinical spectrum of DADA2 has continued to expand since then. It has now been reported in adults as well. Besides vasculitis-related manifestations, hematological, immunological, and autoinflammatory manifestations are now well recognized. More than 100 disease-causing mutations have been described. The decrease in ADA2 enzyme leads to an increased extracellular adenosine level that, in turn, triggers a proinflammatory cascade. The disease is highly variable, and patients carrying same mutation may have different ages of presentation and clinical features. Anti-tumor necrosis factor (TNF) agents are mainstay of treatment of the vasculitis/vasculopathy phenotype. Hematopoietic stem cell transplant (HSCT) has been performed in patients with severe hematological manifestations. Recombinant ADA2 protein and gene therapy hold a promise for future.

Keywords: Adenosine deaminase 2; Autoimmunity; Autoinflammation; Immunodeficiency; Vasculitis/vasculopathy.