AB1090 CECR1/ADA2 MUTATION IN A BRAZILIAN FAMILY

Abstract

<h3>Background</h3> Deficiency of adenosine deaminase 2 (DADA2) is a recently identified disease caused by mutations in the CECR1/ADA2 gene, encoding for adenosine deaminase 2 protein. Clinical presentation is variable and includes early-onset polyarteritis nodosa, hemorrhagic and ischemic strokes, hypogammaglobulinemia and cytopenia <h3>Objectives</h3> To present the clinical cases of two Brazilian siblings with early stroke episodes carrying a homozygous CECR1/ADA2 mutation. <h3>Methods</h3> Chart review of clinical data, laboratory tests and mutation analysis <h3>Results</h3> The index case is a 7-year-old boy who presented to the emergency unit with right lower limb weakness, rhyme deviation and palpebral ptosis, associated with recurrent and intermittent fever, mood change and hypertension. The physical exam revealed drowsiness, lateral and vertical ocular paresis, diplopia, facial palsy, and bilateral ataxia. The brain MRI showed acute left mesencephalic small vessel lacunar stroke, previous right mesencephalic subacute stroke, and cerebellar cavity related with anterior cerebellar artery segmental narrowing. Laboratory tests revealed increased inflammatory markers and anemia. Autoantibodies and viral screening were negative. Renal ultrasound showed a pattern of low resistance in the intrarenal arteries bilaterally. At this time, he was diagnosed as polyarteritis nodosa (PAN). Despite of adequate treatment (cyclosphosphamide and corticosteroids), two new stroke episode occurred at left head of caudate and right thalamus. His brother, a 9-year-old healthy boy at that time, had a previous history of ischemic stroke when he was 4 years old, after receiving a vaccine, with complete recover. Considering this family history and the fact that parents are consanguineous, mutation analysis of CECR1/ADA2 gene was performed and showed homozygosity for the p.Y453C mutation in exon 9 in both siblings and heterozygosity for the same mutation in both parents. Although the eldest boy remained asymptomatic for 5 years without any specific treatment, shortly after the identification of the gene mutation, he presented recurrent fever episodes, myalgia, livedo reticularis and increased inflammatory markers. Anti-TNF treatment was initiated for both patients with good disease control. <h3>Conclusion</h3> DADA2 should be suspected in patients with PAN-like phenotype and history suggestive of an inherited disease (eg.: affected siblings and consanguineous parents) or resistance to conventional treatment. <h3>References</h3> [1] Fayand A, Sarraby G, Belot A, et al. Multiple facets of ADA2 deficiency: Vasculitis, auto-inflammatory disease and immunodeficiency: A literature review of 135 cases from literature Rev. Med Interne 2018 39:297 [2] Caorsi R, Penco F, Grossi, 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: <h3>Disclosure of Interests</h3> None declared