Case Report: Deficiency in Adenosine Deaminase 2 mimicking a childhood Polyarteritis Nodosa: A case report of two siblings with a novel mutation

<ns3:p>Background Polyarteritis Nodosa (PAN) is a systemic vasculitis with cutaneous, renal, cerebral and arterial manifestations. At an early age, it could be very similar to a Deficiency in Adenosine Deaminase 2(DADA2). This genetic autoinflammatory disease is caused by pathogenic variants of the Adenosine Deaminase 2 gene. We present the cases of two siblings with DADA2 misdiagnosed initially as Polyarteritis Nodosa. They were diagnosed with previously unreported pathogenic variants of Adenosine Deaminase 2. Case presentation We report the case of a 21-year-old patient diagnosed with juvenile PAN at the age of 5 years, who presented with recurrent fever, weight loss, livedo reticularis, and subcutaneous nodules. At age 21 years, he presented with headache, vertigo, and tinnitus. MRI revealed small cortical haemorrhages, and CT angiography showed multiple microaneurysms in the peripancreatic, hepatic, and mesenteric arteries. Looking further into the patient’s family history, his 24-year-old brother also had juvenile PAN since the age of 7 years, which was associated with immunoglobulin deficiency. The symptoms at onset included recurrent fever, myalgia, and livedo. In 2020, he was diagnosed with peripheral nervous system manifestations and treated with steroids and azathioprine. ADA2 Deficiency was suspected and confirmed in both patients by genetic screening for a mutation in the gene coding for ADA2 using, Sanger sequencing. Both boys, with non-consanguineous healthy parents, were homozygous for the c.1458–1459insTTGp mutation. (Leu486dup), a novel ADA 2 homozygous pathogenic variant that has not been previously described in the literature. Both patients were treated with Tumor Necrosis Factor inhibitors, with no relapse after a 2-year follow-up. Conclusion This case illustrates the difficulty in distinguishing DADA2 from PAN and highlights the importance of genetic testing in early onset vasculitis. The identified mutation in the gene encoding ADA2 has not been previously described.</ns3:p>