Background/Purpose: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease resulting from a loss-of-function mutation in Cat Eye Syndrome Chromosome Region Candidate 1 (CERC1) gene encoding for ADA2 protein. Patients present with systemic inflammation and vasculopathy.   In this study, we presented the characteristics of the pediatric and adult DADA2 cases.

Methods: Clinical and laboratory features of thirteen DADA2 patients (8 Male, 5 Female), diagnosed at Hacettepe University Pediatric and Adult Rheumatology Department between 2014-2016, have been summarized. Mutations in CECR1 were detected by Sanger sequencing.

Results: Ten patients were homozygous for G47R; one was compound heterozygous for G47R and G47V while two patients were heterozygous for G47R mutation. Nine patients had been followed up with the diagnosis of polyarteritis nodosa (PAN). There was consanguinity in 6 cases, and 2 were siblings. The median (min-max) age at onset of the symptoms and diagnosis was 6.5 (1.5-35) and 17 (3-45) years, respectively. All patients suffered from recurrent episodes of fever and abdominal pain with elevated acute phase reactants. Livedo reticularis (n= 12, (92.3%)), erythema nodosum (n=6, (46.2%)), raynaud’s phenomenon (n=4, (30.8%)) and digital ulcers (n=1, (7.7%)) were common skin manifestations. Neurological and musculoskeletal involvement was;  in the form of myalgia (n = 13, (100%)), arthralgia (n= 12, (92.3%)), arthritis (n= 9, (69.2%)), peripheral neuropathy (n=7, (53.8%)), ischemic stroke (n=7, (53.8%)), strabismus (n=5, (38.5%)), hemorrhagic stroke (n=2, (15.4%)), spinal cord atrophy (n = 1, (7.7%)), and optic neuritis (n = 1, (7.7%)) . One patient had been diagnosed with core myopathy through co-incidental muscle biopsy finding. Eight patients had aneurysms in medium-sized abdominal visceral arteries (hepatic artery, renal artery, and superior mesenteric artery). As renal involvement, one patient had focal segmental glomerulosclerosis (collapsing variant), one mesangial proliferative glomerulonephritis, and one had renal amyloidosis. There was testicular involvement in 3 (23.1%) patients and one had testicular torsion. One patient had intestinal perforation. Two adult patients died soon after diagnosis of DADA2. One patient was asymptomatic on only colchicine for almost 10 years. Rest of the patients responded well to etanercept therapy.

Conclusion: ADA2 deficiency is a recently defined disease and the data about its phenotype increases with the introduction of new cases with different symptoms. Stroke, peripheral neuropathy, livedo reticularis, myalgia, recurrent episodes of fever and recurrent abdominal pain are important findings to suspect DADA2. In our series, we have described for the first time spinal cord atrophy, core myopathy, and mesangial proliferative glomerulonephritis in DADA2 patients.