Deficiency of Adenosine Deaminase 2 (DADA2), an Inherited Cause of Polyarteritis Nodosa and a Mimic of Other Systemic Rheumatologic Disorders

  • Hasan Hashem
  • Susan J Kelly
  • Nancy J Ganson
  • Michael S Hershfield
Orphan Diseases (B Manger, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Orphan Diseases


Purpose of Review

A new autoinflammatory disease, deficiency of adenosine deaminase 2 (DADA2), caused by mutations in the CECR1 gene, was first reported in 2014. This review aims to update progress in defining, treating, and understanding this multi-faceted disorder.

Recent Findings

DADA2 was first described in patients with systemic inflammation, mild immune deficiency, and vasculopathy manifested as recurrent stroke or polyarteritis nodosa (PAN). More than 125 patients have now been reported, and the phenotype has expanded to include children and adults presenting primarily with pure red cell aplasia (PRCA), or with antibody deficiency. Age of onset and clinical severity vary widely, even among related patients, and are not clearly related to CECR1 genotype. Inflammatory features often respond to anti-TNF agents, but marrow failure and severe immune deficiency may require hematopoietic stem cell transplantation.


ADA2 is expressed and secreted by monocytes and macrophages, but its biological function and the pathogenesis of DADA2 are uncertain and will remain an important area of research. Pre-clinical investigation of ADA2 replacement therapy and CECR1-directed gene therapy are warranted, but complicated by the absence of a suitable animal model.


Monogenic autoinflammatory disorder CECR1 Vasculopathy Polyarteritis nodosa Stroke Immune deficiency Pure red cell aplasia Macrophage polarization TNF inhibitor Hematopoietic stem cell transplant Adenosine deaminase Whole-exome sequencing 


Compliance with Ethical Standards

Conflict of Interest

Michael S Hershfield receives grant support from Leadiant Biosciences, Inc., the manufacturer of Adagen, a PEGylated adenosine deaminase used to treat patients with ADA1 deficiency.

Hasan Hashem, Susan J Kelly, and Nancy J Ganson declare they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Hasan Hashem
    • 1
  • Susan J Kelly
    • 2
  • Nancy J Ganson
    • 2
  • Michael S Hershfield
    • 2
    • 3
  1. 1.King Hussein Cancer CenterAmmanJordan
  2. 2.Duke University School of MedicineDurhamUSA
  3. 3.Duke University Medical CenterDurhamUSA

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