AB1039 ADA2 DEFICIENCY PRESENTING AS INFANTILE POLYARTERITIS NODOSA
Authors: GraÇa Loureiro, Diana Oliveira, Sara Ganhão, Francisca Aguiar, Mariana Rodrigues, Iva Brito
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Polyarteritis nodosa (PAN) is a rare form of primary systemic vasculitis with heterogeneous presentations, treatments and disease course. There have been improvements in understanding of certain causes of PAN such as the association of the monogenic disorder Deficiency of Adenosine Deaminase 2 (DADA2) with a PAN phenotype. This described autoinflammatory disease is caused by loss-of-function homozygous or compound heterozygous mutations in CECR1 and can be characterised by an early onset vasculopathy with clinical and histopathological features of PAN associated with haemorrhagic and ischaemic strokes. <h3>Objectives</h3> We report a case of a 14 year-old boy, with a prenatal diagnosis of Klinefelter syndrome, whose parents are first cousins. <h3>Methods</h3> Review of patients clinical records and scientific literature. <h3>Results</h3> During his first two years of age, he suffered two small strokes, was investigated in another Hospital and no diagnosis was made. At 4 years of age he was admitted to another hospital for prolonged fever and arthralgia. At age 5 he was admitted to our hospital for fever, arthralgia and myalgia. He later developed a medular stroke and arterial hypertension. Due to suspected PAN he underwent a renal angiogram which confirmed our suspicion. He completed induction treatment with IV cyclophosphamide (6 months), steroids, acetylsalicylic acid (ASA), warfarin and ramipril, followed by maintenance with azathioprine (AZA). While on remission, 2 weeks after after stopping warfarine he suffered a transient ischemic attack; brain-MRI showed a small <i>de novo thalamic</i> lesion. CECR1 testing revealed c.1226C&gt;A variant in homozygosity, his parents are both carriers. ADA2 enzymatic activity was then tested and was absent, which confirms the diagnosis. IgM levels are low. He started adalimumab and stopped warfarin, aspirin and AZA. He mantains follow-up, with no sequelae to his strokes and apparent clinical remission. <h3>Conclusion</h3> The age of onset and clinical manifestations of DADA2 vary widely and are not clearly related to the genotype. Although this variant in CECR1 was of uncertain pathological significance, the absence of ADA2 enzymatic activity confirms the diagnosis. Timely diagnosis and treatment with anti-TNF drugs are thought to be crucial to prevent severe complications. Also, these patients should not be treated with ASA or anticoagulants which are frequently used in PAN patients. Low IgM levels can be a clue to raise the suspicion. Lack of long term outcome data in children with DADA2 makes the prognosis uncertain and underlines the need to maintain a lifelong follow-up. <h3>References</h3> [1] Zhou Q et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014 Mar 6;370(10):911-20 [2] Navon E et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014 Mar 6;370(10):921-31. <h3>Acknowledgement</h3> The authors wish to thank Gustavo M Santo for his cooperation. <h3>Disclosure of Interests</h3> None declared