Two independent studies describe a new vascular inflammatory syndrome caused by loss-of-function mutations in CECR1, which encodes the extracellular adenosine deaminase ADA2. Ivona Aksentijevich and colleagues (N. Engl. J. Med. 370, 911–920, 2014) performed exome sequencing of three unrelated subjects with a spectrum of phenotypes that included recurrent fevers and early-onset stroke, discovering biallelic mutations in CECR1 in all three cases. They subsequently identified six other individuals with biallelic CECR1 mutations and overlapping clinical features. Separately, Ephrat Levy-Lahad and colleagues (N. Engl. J. Med. 370, 921–931, 2014) performed exome sequencing of several individuals of Georgian Jewish ancestry diagnosed with polyarteritis nodosa, a systemic necrotizing vasculitis, and identified a homozygous missense mutation in CECR1 in all cases. They subsequently found compound heterozygous CECR1 mutations in individuals of German and Turkish ancestry with similar clinical presentations. In both studies, the mutations were associated with reduced ADA2 activity in plasma. Given the known biological roles of ADA2, the disease phenotypes may result from upregulation of the adenosine inflammatory response pathway or from loss of ADA2-mediated growth factor activity.