Deficiency of Adenosine Deaminase 2 (DADA2)

Abstract

Deficiency of adenosine deaminase type 2 (DADA2) is a recently discovered, pathogenetically complex autoinflammatory syndrome with features of autoinflammation, immunodeficiency, and autoimmunity. The disease is highly variable in regard to age at onset, disease severity, and organ involvement but typically presents as a childhood-onset vasculopathy resembling polyarteritis nodosa (PAN). Patients with DADA2 characteristically present with livedo racemosa, purpura, leg ulcers, Raynaud’s phenomenon, and digital necrosis and in more severe cases with peripheral neuropathy, and early-onset hemorrhagic and ischemic strokes. Other symptoms include subcutaneous nodules, recurrent fevers, hepatosplenomegaly, ophthalmologic manifestations, hypertension, musculoskeletal symptoms, marrow failure, and hypogammaglobulinemia. Evaluation of ADA2 enzymatic activity and genetic analysis for CECR1 gene mutations may aid in the diagnosis. Treatment for DADA2 is not yet well established and should be based on the individual presentation and severity of the disease.