Background Deficiency of adenosine deaminase 2 (DADA2) associated with mutations in the CECR1 gene causes a vasculopathy with systemic inflammation. The full clinical spectrum and management of these patients are yet to be defined.

Objectives We aimed to assess the characteristics and course of our DADA2 patients and compare them to the cases in the literature.

Methods This is a descriptive case series of Turkish patients diagnosed with DADA2 at the Hacettepe University. For mutation analysis we performed Sanger sequencing of 10 protein-coding exons of CECR1.

Results We report five Turkish patients with DADA2. All were initially diagnosed as polyarteritis nodosa (PAN) due to the systemic nature of their disease fulfilling the classification criteria for the disease and all but one having necrotizing arteritis lesions based on skin biopsy. Two had arterial aneurysms. All had skin lesions varying from livedo racemosa to necrotic ulcers on fingers. Four had varying features and degrees of central nervous system involvement. Mutation analysis showed homozygosity for the p.G47R (c. 139G>A) mutation in the CECR1 gene in all five patients. All were initially treated with corticosteroids; however none responded. One adult patient with extensive systemic amyloidosis was resistant to immunosuppressive and plasma treatments and died due to necrotizing pneumonia. The second adult patient partially improved with etanercept and plasmapheresis. The pediatric patients had better prognosis; one is on monthly plasma replacement and the other one on etanercept treatment with a good control of disease. The patient with a previous diagnosis of cutaneous PAN has responded to mycophenolate mofetil treatment. At literature review there are 44 DADA2 patients reported, including five ours. Patients who are homozygous for the p.G47R mutation have fewer strokes and predominantly a PAN-like phenotype compared to patients with other mutations.

Conclusions DADA2 may be classified as a secondary vasculitis due to a probable cause. The response to immunosuppressive treatment and the B cell defects in these patients places the disease in between the spectrum of innate and adaptive immune dysregulation. A genotype-phenotype correlation may exist for DADA2, with the G47R mutation causing a predominantly PAN-like phenotype while other mutations causing predominantly a vasculopathy with central nervous system disease (especially strokes).

References

1. Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 2014;370(10):921-931

2. Zhou Q, Yang D, Ombrello AK, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 2014;370(10):911-920

3. Garg N, Kasapcopur O, Foster J, 2nd, et al. Novel adenosine deaminase 2 mutations in a child with a fatal vasculopathy. Eur J Pediatr 2014;173(6):827-830

Disclosure of Interest None declared