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Background:Progressive pseudorheumatoid dysplasia(PPRD) is considered as a degenerative genetic bone disorder. It is caused by loss of function mutation in WNT-1 inducible signaling pathway protein-3(WISP-3)1. WISP-3 gene function is required for the normal function of cartilage and skeletal development. The patients are normal at birth and start developing symptoms around 3-6 years of age2. The disease is characterised by stiffness, pain, deformity due to enlargement of the ends of short and long bones. Often, such patients are misdiagnosed as Juvenile idiopathic arthritis(JIA). In general, PPRD being considered as non-inflammatory disease, immunosuppressants or disease modifying anti rheumatic drugs(DMARDS) like methotrexate treatment are not used for treatment.Objectives:We report a patient with characteristic findings of PPRD but with coexisting clinical and imaging evidence of inflammation.Methods:16 year old male boy born of third degree consanguineous asymptomatic parents presented with progressive swelling, deformity of bilateral small and large joints of upper and lower limbs. He also had pain in both hip and knee for past two years. Pain is associated with difficulty in walking and squatting. On examination he had bony enlargement around bilateral elbow, wrist, proximal and distal interphalangeal joints(Figure 1A). He also had restriction of bilateral hip movements and swelling of bilateral knee with effusion. He had exaggerated lumbar lordosis and flexion deformity of bilateral hip, knee. His blood counts, ESR, CRP were normal. Analysis of Knee joint synovial fluid showed cell count of 200/mm3 with no crystals and sterile culture. USG knee showed evidence of synovial thickening with increased power Doppler signals. Skeletal survey showed typical findings of PPRD with enlargement of epiphysis and osteoarthritis changes(Figure 1B). MRI hip showed minimal effusion, synovial thickening, edema with STIR hyperintensity and enlargement of bilateral femoral epiphysis. MRI knee showed minimal effusion, marrow edema in patella(Figure 1C, arrow head), femoral condyle, diffuse synovial thickening with contrast enhancement(Figure 1D, arrow) and deformed patellar contour. Immunological tests showed negative RF, ACPA and positive ANA(Hep2) speckled 4+. Immunoblot for ENA was negative. His ophthalmological evaluation showed no evidence of uveitis.Figure 1.Clinical picture showing typical hand deformity and swelling at bone ends(A), hand radiograph showing epiphyseal enlargement(B), MRI knee T2 STIR showing bone marrow edema(arrow head) in patella(C) and synovial thickening(arrow) with contrast enhancement in fat saturated T1 MRI with contrast.Results:Patient tested positive for homozygous mutation in WISP-3 gene. He was treated with ibuprofen and supportive measures. Orthopedic consultation obtained and planned for hip, knee replacement during follow up. Follow up imaging and acute phase response was advised after three months.Conclusion:Although PPRD was classically described as a degenerative disease, the findings presented in our case show coexisting inflammation. Bone marrow edema in weight bearing areas, synovial effusion may be explained as part of cartilage degeneration like in osteoarthritis but synovial hypertrophy with contrast enhancement, power Doppler signals in ultrasound, ANA positivity may be signs of coexisting inflammatory or autoimmune phenomenon.References:[1]Hurvitz JR, Suwairi WM et al. Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. Nat Genet. 1999 Sep;23(1):94-8. doi: 10.1038/12699. PMID: 10471507.[2]Garcia Segarra N, Mittaz L et al. The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): a review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):217-29. doi: 10.1002/ajmg.c.31333. Epub 2012 Jul 12. PMID: 22791401.Disclosure of Interests:None declared

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Background:Deficiency of Adenosine Aminase deficiency 2 is monogenic disease presenting with multisystem involvement of vasculitis,Stroke1,hematological manifestations. We hereby present a young child who presented with PRES initially and later diagnosed as DADA2.Only one case of DADA2 presenting as PRES is reported so far2.This case highlights the atypical presentation of DADA2.Objectives:A case report to highlight the rare presentation of DADA2 vasculits.Methods:8 year old developmentally normal male child,born out of consanguineous marriage presented with with fever,abdominal pain, seizures 1 year back.Ultrasound of abdomen revelaed mesenteric lymphadenitis and MRI Brain was suggestive of Meningoencephalitis.He was managed with antivirals and antibiotics then.6 months later,he had fever,skin rash,pain abdomen,status epilepticus,hypertension followed by gangrene of fingers and toes.APLA,ANA,ANCA workup was negative. Complete Hemogram was normal. CRP was 130mg/dl. CT Abdomen was normal and no evidence of aneurysms. Renal Doppler Ultrasound was normal.CT upper limb showed left radial and ulnar artery significant narrowing with patchy occlusion. MRI Brain showed bilateral fronto parietal,occipital,putamen,left insula and subcortical and cortical T2W FLAIR hyperintensity without diffusion restriction suggestive of PRES. He was diagnosed as Childhood Polyarteritis Nodosa and treated with cyclophosphamide. Genetic Analysis of ADA2(CECR1) gene mutation by Sanger Sequencing of exons 2 to 10 showed a known variant (rs202134424) in ADA2 gene.Figure 1.Gangrene of left 1-5th digits and right 4th and 5th digit resorptionFigure 2.T2W FLAIR image showing bilateral fronto parietal,occipital,putamen,left insula and subcortical and cortical hyperintensity without diffusion restriction suggestive of PRES.Results:He was started on Infliximab and is on follow up. No further events noted so far.Rehabilitation of left upper hand was done.Conclusion:DADA2 can present with varied CNS manifestations like infarct,hemorrhage,aneurysms and PRES.High index of suspicion and early recognition can help in maintaining vascular integrity.References:[1]Ganhão S, Loureiro G, Oliveira D, dos-Reis-Maia R, Aguiar F, Quental R et al. Two cases of ADA2 deficiency presenting as childhood polyarteritis nodosa: novel ADA2 variant, atypical CNS manifestations, and literature review. Clinical Rheumatology. 2020;39(12):3853-3860.[2]Sharma A, Naidu G, Sharma V, Jha S, Dhooria A, Dhir V et al. Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India. Arthritis & Rheumatology. 2020;73(2):276-285.Disclosure of Interests:None declared