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Deficiency of Adenosine Deaminase 2 (DADA2)

  • Amanda OmbrelloEmail author
  • Reeval Segel
Chapter

Abstract

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease resulting from mutations in ADA2 (formerly named CECR1). Initially described by two groups in 2014, additional reports have documented that the phenotypic expression is quite broad. Although commonly presenting in childhood, patients can present throughout their lives with varying forms of inflammatory, neurologic, hematologic, and immunologic phenotypes. Frequently reported disease manifestations include lacunar strokes, non-cirrhotic portal hypertension, immunodeficiencies, and bone marrow involvement that can include an overt pancytopenia ranging to cell-specific immune destruction. The role of adenosine deaminase 2 (ADA2) remains incompletely understood. The lack of ADA2 in patients with DADA2 results in endothelial cell fragility and a skewing of macrophage development toward the inflammatory, M1 macrophage. Current treatment options are tailored toward the individual clinical presentations but the utilization of anti-tumor necrosis factor (TNF) medications has been highly effective at reducing the risk for stroke. Hematopoietic stem cell transplant offers a potential cure for the disease.

Keywords

Adenosine deaminase 2 DADA2 ADA2 Autoinflammation Polyarteritis nodosa Stroke Cytopenia Immunodeficiency Hematopoietic stem cell transplantation Anti-tumor necrosis factor drugs 

Abbreviations

ADA1

Adenosine deaminase 1

ADA2

Adenosine deaminase 2

ADGF

ADA-related growth factor

CERC1

Cat eye syndrome chromosome region, candidate 1

DADA2

Deficiency of adenosine deaminase 2

FFP

Fresh frozen plasma

GvHD

Graft versus host disease

HSCT

Hematopoietic stem cell transplant

IL

Interleukin

MPO

Myeloperoxidase

MRA

Magnetic resonance angiography

NIH

National Institutes of Health

NRH

Nodular regenerative hyperplasia

PAN

Polyarteritis nodosa

PHA

Phytohemagglutinin

PMA

Phorbol myristate acetate

SCID

Severe combined immunodeficiency

shRNA

Short hairpin RNA

TNF

Tumor necrosis factor

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.National Human Genome Research InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Medical Genetics Institute and Pediatrics, Shaare Zedek Medical CenterHebrew University School of MedicineJerusalemIsrael

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