SAT0244 EXPANDING SPECTRUM OF ADENOSINE DEAMINASE 2 (DADA2) MANIFESTATIONS: EXPERIENCE 13 PATIENTS FROM INDIA
Authors: Aman Sharma, Gsrsnk Naidu, Ramesh Jois, Chengappa Kavadichanda, Rajkiran Dudam, Sanjay Jain, Vir Negi, Pui.Y Lee
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Deficiency of adenosine deaminase 2 (DADA2) is a recently described hereditary autoinflammatory disease with limited published literature [1-5]. There are no previous case series published from Asia. <h3>Objectives:</h3> To describe the clinical features and treatment responses of patients diagnosed with DADA2 from India. <h3>Methods:</h3> Patients diagnosed with DADA2 at 4 different centres in India were included. Details of clinical features, laboratory investigations, ADA2 activity, genetic analysis of CECR1 gene, therapy received and outcomes were noted. <h3>Results:</h3> A total of 13 patients (12 Indians and one Syrian) were diagnosed with DADA2 between April 2017 and January 2019. The median age was 22 years (range: 7-39 years) and 8 (61.5%) patients were males. The diagnosis was made at a median duration of 30 months (range: 1-360 months) from the onset of first symptom. Figure 1 shows the various clinical manifestations. One patient had unknown manifestation of bad obstetric history mimicking APLA syndrome. ESR (median: 49.5 mm/hr; range: 15-130 mm/hr) was raised in all except one patient who was in remission at the time of diagnosis. CRP value was available in 11 patients and was elevated in all (median: 51.4 mg/L; range: 17.6-140 mg/L). Immunoglobulin levels assessed in 4 patients were normal. Neuroimaging done in nine patients showed infarcts in 5, bleed in 3, multiple aneurysms and features of PRES in one patient each. Abdominal microaneurysms were noted in 5 patients. Arterial occlusion of peripheral limb vessels was noted in 2 patients. ADA2 activity was assessed in 9 patients and all had nearly undetectable activity. CECR1 gene mutation analysis was available in 9 patients: 8 patients were homozygous for p.(Gly47Arg) missense mutation at exon 2 of CECR1 gene while one patient displayed compound heterozygosity for two novel mutations, P.(Leu188Val) in exon 4 and C.753+2 T&gt;A in intron 4 of CECR1 gene. Eight patients were started on anti-TNF drugs (adalimumab in 7 and etanercept in 1). One patient required higher doses of adalimumab (40mg followed by 120mg at week 1 and 80mg at week 2) for severe gastrointestinal involvement but later died due to disseminated herpes infection. Rest of the seven patients started on anti-TNF drugs achieved disease control. Our patients had CNS, eye and GI manifestations lower than those reported by Zhou et al<sup>1</sup> but higher than those reported by Nanthapisal et al<sup>2</sup> and Navon Elkan et al<sup>4</sup> <h3>Conclusion:</h3> The spectrum of clinical presentations in Indian patients is different from those reported in previous cohorts. Anti TNF therapy was effective in majority. <h3>References</h3> [1] Zhou Q, Yang D, Ombrello AK, et al. Early onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014; 370: 911–920. [2] Nanthapisal S, Murphy C, Omoyinmi E, et al. Deficiency of adenosine deaminase Type 2: a description of phenotype and genotype in fifteen cases. Arthritis Rheumatol. 2016; 68: 2314–2322. [3] Caorsi R, Penco F, Grossi A, et al. ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study. Ann Rheum Dis. 2017; 76: 1648–1656. [4] Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014; 370: 921-31. [5] Sharma A, Naidu GSRSNK, Chattopadhyay A, et al. Novel CECR1 gene mutations causing deficiency of adenosine deaminase 2, mimicking antiphospholipid syndrome. Rheumatology. 2019; 58: 181-2. <h3>Disclosure of Interests:</h3> None declared