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AB0972 Childhood onset stroke and vasculitis associated with deficiency of adenosine deaminase 2 (DADA2)
  1. V Paisal1,
  2. E Al-Abadi1,
  3. T Southwood1,
  4. E Wassmer2
  1. 1Paediatric Rheumatology
  2. 2Paediatric Neurology, Birmingham Children's Hospital, Birmingham, United Kingdom


Background The deficiency of Adenosine Deaminase 2 (DADA2) is a rare autosomal recessive condition resulting from mutations in CECR1 (Cat Eye Syndrome Chromosome Region 1) gene, mapped to chromosome 22q11.1. It is a type of autoinflammatory disease, mainly characterised by early-onset polyarteritis, haemorrhagic, ischemic strokes and hypogammaglobulinemia (1). We report a case of 7-year boy presenting with haemorrhagic stroke and vasculitis responding to immunosuppression with Anti-TNF drug.

Objectives A 7 year boy presented to the emergency department with reduced consciousness, headaches and nose bleeds. Initial imaging showed an intraparenchymal haemorrhage requiring frontal craniotomy and evacuation of the haematoma. This acute presentation was preceded by a history of recurrent fevers, weight loss, testicular pain, erythema nodosum and tender lymph nodes.

Methods The laboratory findings revealed anaemia, ESR of up to 61mm/h, C-reactive protein 100, normal immunoglobulins, positive Anti nuclear antibody (ANA), mildly raised antibodies to double stranded DNA (dsDNA) and Proteinase 3 antibody. Skin biopsy confirmed panniculitis. CT imaging and angiography of the head at the time of acute presentation showed intraparenchymal haemorrhage and aneurysm of the left middle cerebral artery. Further CT angiography of the whole body revealed renal and liver microaneurysms. A provisional diagnosis of Polyarteris nodosa was made and started on steroids and cyclophosphamide. He had further genetic testing, showing mutation in CECR1, leading to Adenosine deaminase 2 deficiency. Patient responded to cyclophosphamide induction regime, which was followed by Etanercept.

Results We report a case of ADA2 deficiency presenting initially with features of an autoinflammatory disorder, complicated by acute stroke secondary to haemorrhage. Our patient exhibited most of the clinical symptoms previously reported in ADA2 deficiency, including its association with polyarteritis nodosa (2). Although, he did not exhibit hypogammaglobulinaemia (3) which has been reported, interestingly, he was positive for markers of autoimmunity (ANA, ANCA) (4). It has been reported that treatment with anti-TNF and IL-6 (5) could lead to improvement, and our patients initial response to cyclophosphamide was excellent, followed by continued treatment with Etanercept.

Conclusions Screening for adenosine deaminase 2 deficiency should be considered in all children presenting with neurological symptoms and features of vasculitis.


  1. Roberta Caorsi, Federica Penco, Francesca Schena and Marco Gattorno. Monogenic polyarteritis: the lesson of ADA2 deficiency.Pediatric Rheumatology 2016. DOI: 10.1186/s12969–016–0111–7.

  2. Nanthapisal S, Murphy C, Omoyinmi E, Hong Y, Standing, A, Berg S, Ekelund M, Jolles S, Harper L, Youngstein T, Gilmour K, Klein N, Eleftheriou D, Brogan PA. Deficiency of adenosine deaminase type 2 (DADA2): a description of phenotype and genotype in 15 cases. Arthritis and Rheumatism.

  3. Segel R, King MC, Levy-Lahad E. Mutant ADA2 in vasculopathies. N Engl J Med 2014;371:481–2. doi:10.1056/NEJMc1407114.

  4. Zhou Q, Yang D, Ombrello AK et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 2014;370:911–20. doi:10.1056/NEJMoa1307361.

  5. Van Eyck L, Liston A, Wouters C. Mutant ADA2 in vasculopathies. N Engl J Med 2014;371:480 doi:10.1056/NEJMc1405506#SA4.


Disclosure of Interest None declared

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