Adenosine deaminase 2 deficiency

This article is about a vasculitis syndrome caused by ADA2 gene mutations. For the metabolic disorder caused by ADA1 gene mutations, see Adenosine deaminase deficiency.
Deficiency of Adenosine Deaminase 2
Other namesDADA2
Autosomal recessive pattern is the inheritance manner of this condition
SpecialtyMedical genetics, Pediatrics, Rheumatology, Neurology, Dermatology, Immunology, Hematology
Usual onsetVariable, but commonly in early childhood
DurationLifelong
CausesMutations in the ADA2 gene
Diagnostic methodGenetic or Enzymatic Testing

Deficiency of Adenosine deaminase 2 (DADA2) is a monogenic disease associated with systemic inflammation and vasculopathy that affects a wide variety of organs in different patients. As a result, it is hard to characterize a patient with this disorder. Manifestations of the disease include but are not limited to recurrent fever, livedoid rash (reticularis or racemosa), various cytopenias, stroke, immunodeficiency, and bone marrow failure.[1][2] Symptoms often onset during early childhood, but some cases have been discovered as late as 65 years old.[3]

DADA2 is caused by mutations in the ADA2 gene, and is inherited in an autosomal recessive manner. The protein product of this gene, adenosine deaminase 2 (ADA2), is an extracellular enzyme that breaks down adenosine and may also serve as a growth factor. Pathogenic mutations decrease this enzymatic activity in patient blood, leading to disease manifestations. However, mutational status and residual enzyme activity levels do not explicitly correlate with the type of disease a patient displays.[4][2][1]

The most common treatment for DADA2 is TNF inhibitors. This therapy tends to prevent vasculitis-related manifestations such as rash and stroke,[5][6] but does not perform well in individuals presenting with severe hematologic and immunologic abnormalities such as bone marrow failure or severe recurrent infections.[7] In these cases, hematopoietic stem cell transplantation has led to major improvements in the vascular, hematologic, and immunologic manifestations of disease.[8]

  1. ^ a b Lee PY (2018). "Vasculopathy, Immunodeficiency, and Bone Marrow Failure: The Intriguing Syndrome Caused by Deficiency of Adenosine Deaminase 2". Frontiers in Pediatrics. 6: 282. doi:10.3389/fped.2018.00282. PMC 6200955. PMID 30406060.
  2. ^ a b Meyts I, Aksentijevich I (July 2018). "Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment". Journal of Clinical Immunology. 38 (5): 569–578. doi:10.1007/s10875-018-0525-8. PMC 6061100. PMID 29951947.
  3. ^ Bourgeois G, Richard M, Danset M, Pérard L, Breton AL, Berthoux E (March 2021). "Deficiency of adenosine deaminase 2 diagnosed at 65 years of age". Lancet. 397 (10277): 913. doi:10.1016/S0140-6736(20)32660-X. PMID 33676630. S2CID 232116912.
  4. ^ Lee PY, Kellner ES, Huang Y, Furutani E, Huang Z, Bainter W, et al. (June 2020). "Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2)". The Journal of Allergy and Clinical Immunology. 145 (6): 1664–1672.e10. doi:10.1016/j.jaci.2019.12.908. PMC 7282972. PMID 31945408.
  5. ^ Ombrello AK, Qin J, Hoffmann PM, Kumar P, Stone D, Jones A, et al. (April 2019). "Treatment Strategies for Deficiency of Adenosine Deaminase 2". The New England Journal of Medicine. 380 (16): 1582–1584. doi:10.1056/NEJMc1801927. PMC 7372950. PMID 30995379.
  6. ^ Sharma A, Naidu G, Sharma V, Jha S, Dhooria A, Dhir V, et al. (February 2021). "Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India". Arthritis & Rheumatology. 73 (2): 276–285. doi:10.1002/art.41500. PMC 7902299. PMID 32892503.
  7. ^ Conticini E, Sota J, Falsetti P, Lamberti A, Miracco C, Guarnieri A, et al. (April 2021). "Biologic drugs in the treatment of polyarteritis nodosa and deficit of adenosine deaminase 2: A narrative review". Autoimmunity Reviews. 20 (4): 102784. doi:10.1016/j.autrev.2021.102784. PMID 33609794. S2CID 231979636.
  8. ^ Hashem H, Kumar AR, Müller I, Babor F, Bredius R, Dalal J, et al. (December 2017). "Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2". Blood. 130 (24): 2682–2688. doi:10.1182/blood-2017-07-798660. PMC 5731089. PMID 28974505.