Definition
The deficiency of adenosine deaminase type 2 (DADA2) is an autosomal recessive disease resulting from biallelic, loss-of-function mutations in ADA2 (formerly known as CECR1), located in chromosome 22q11.1. DADA2 is characterized by systemic vasculitis and features of both autoinflammation and immunodeficiency (MIM#615688).
Introduction and Background
DADA2 was initially reported in 2014 in patients who presented with inflammatory phenotypes that resembled vasculitis and polyarteritis nodosa (PAN) and recurrent ischemic and/or hemorrhagic strokes (Zhou et al. 2014; Navon Elkan et al. 2014). Since the initial publications, the clinical phenotype has expanded significantly to include additional disease manifestations. The identification of DADA2 expands the family of adenosine deaminase-related diseases from the most commonly known severe combined immune...
References
Ben-Ami T, Revel-Vilk S, Brooks R, et al. Extending the clinical phenotype of adenosine deaminase 2 deficiency. J Pediatr. 2016;177:316–320.
Caorsi R, Penco F, Schena F, Gattorno M. Monogenic polyarteritis: the lesson of ADA2 deficiency. Pediatr Rheumatol Online J. 2016;14:51.
Caorsi R, Penco F, Grossi A, et al. ADA2 deficiency (DADA2) as an unrecognized cause of early onset polyarteritis nodosa and stroke: a multicenter national study. Ann Rheum Dis. 2017;76:1648–56.
Hashem H, Kumar AR, Müller I, et al. Hematopoietic stem cell transplantation rescues the hematological, immunological and vascular phenotype in DADA2. Blood. 2017;130:2682–8.
Michniacki TF, Hannibal M, Ross CW, et al. Hematologic manifestations of deficiency of adenosine deaminase 2 (DADA2) and response to tumor necrosis factor inhibition in DADA2-associated bone marrow failure. J Clin Immunol. 2018;38:166–73.
Nanthapisal S, Murphy C, Omoyinmi E, et al. Deficiency of adenosine deaminase type 2: a description of phenotype and genotype in fifteen cases. Arthritis Rheumatol. 2016;68:2314–22.
Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014;370:921–31.
Ombrello AK, Qin J, Hoffmann P, et al. Treatment strategies for the deficiency of adenosine deaminase 2. N Engl J Med. 2019;380:1582–4.
Pichard DC, Ombrello AK, Hoffmann P, Stone DL, Cowen EW. Early-onset stroke, polyarteritis nodosa (PAN), and livedo racemosa. J Am Acad Dermatol. 2016;75:449–53.
Sahin S, Adrovic A, Barut K, Ugurlu S, Turanli E, Ozdogan H, Kasapcopur O. Clinical, imaging and genotypical features of three deceased and fiver surviving cases with ADA2 deficiency. Rheumatol Int. 2018;38(1):129–136.
Schepp J, Proietti M, Frede N, et al. Screening of 181 patients with antibody deficiency for deficiency of adenosine deaminase 2 sheds new light on the disease in adulthood. Arthritis Rheumatol. 2017;69:1689–700.
Trotta L, Martelius T, Siitonen T, et al. ADA2 deficiency: clonal lymphoproliferation in a subset of patients. J Allergy Clin Immunol. 2018;141:1534–7.
Vu D, Gonzalez RG, Schaefer PW. Conventional MRI and MR angiography of stroke. In: Gonzalez RG, Hirsch JA, Koroshetz WJ, Lev MH, Schaefer P, editors. Acute ischemic stroke: imaging and intervention. Berlin: Springer; 2006. p. 115–37.
Zavialov AV, Engstrom A. Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity. Biochem J. 2005;391:51–7.
Zavialov AV, Garcia E, Glaichenhaus N, et al. Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages. J Leukoc Biol. 2010;88:279–90.
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.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2020 This is a U.S. Government work and not under copyright protection in the U.S.; foreign copyright protection may apply
About this entry
Cite this entry
Ombrello, A.K. (2020). DADA2. In: MacKay, I., Rose, N. (eds) Encyclopedia of Medical Immunology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9209-2_118-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-9209-2_118-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-9209-2
Online ISBN: 978-1-4614-9209-2
eBook Packages: Springer Reference MedicineReference Module Medicine