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Adenosine deaminase deficiency

MedGen UID:
120610
•Concept ID:
C0268124
•
Disease or Syndrome
Synonym: ADA Deficiency
SNOMED CT: ADA - Adenosine aminohydrolase deficiency (44940001); Deficiency of adenosine deaminase (44940001); Adenosine deaminase deficiency (44940001); ADA deficiency (44940001); Adenosine aminohydrolase deficiency (44940001)

Definition

An autosomal recessive deficiency of the purine salvage enzyme adenosine deaminase which results in Severe Combined Immunodeficiency Disease (SCID). The most common form of SCID, accounting for about 50% of autosomal recessive cases. The first disease for which gene therapy was applied. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAdenosine deaminase deficiency

Professional guidelines

PubMed

Updated Management Guidelines for Adenosine Deaminase Deficiency.
Grunebaum E, Booth C, Cuvelier GDE, Loves R, Aiuti A, Kohn DB
J Allergy Clin Immunol Pract 2023 Jun;11(6):1665-1675. Epub 2023 Feb 1 doi: 10.1016/j.jaip.2023.01.032. PMID: 36736952
Newborn tandem mass spectroscopy screening for adenosine deaminase deficiency.
Hartog N, Hershfield M, Michniacki T, Moloney S, Holsworth A, Hurden I, Fredrickson M, Kleyn M, Walkovich K, Secord E
Ann Allergy Asthma Immunol 2022 Dec;129(6):776-783.e2. Epub 2022 Jul 30 doi: 10.1016/j.anai.2022.07.016. PMID: 35914665
Gene Therapy for the Treatment of Primary Immune Deficiencies.
Kuo CY, Kohn DB
Curr Allergy Asthma Rep 2016 May;16(5):39. doi: 10.1007/s11882-016-0615-8. PMID: 27056559Free PMC Article

Recent clinical studies

Etiology

Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency.
Kohn DB, Booth C, Shaw KL, Xu-Bayford J, Garabedian E, Trevisan V, Carbonaro-Sarracino DA, Soni K, Terrazas D, Snell K, Ikeda A, Leon-Rico D, Moore TB, Buckland KF, Shah AJ, Gilmour KC, De Oliveira S, Rivat C, Crooks GM, Izotova N, Tse J, Adams S, Shupien S, Ricketts H, Davila A, Uzowuru C, Icreverzi A, Barman P, Campo Fernandez B, Hollis RP, Coronel M, Yu A, Chun KM, Casas CE, Zhang R, Arduini S, Lynn F, Kudari M, Spezzi A, Zahn M, Heimke R, Labik I, Parrott R, Buckley RH, Reeves L, Cornetta K, Sokolic R, Hershfield M, Schmidt M, Candotti F, Malech HL, Thrasher AJ, Gaspar HB
N Engl J Med 2021 May 27;384(21):2002-2013. Epub 2021 May 11 doi: 10.1056/NEJMoa2027675. PMID: 33974366Free PMC Article
Gene therapy for primary immunodeficiencies.
Fox TA, Booth C
Br J Haematol 2021 Jun;193(6):1044-1059. Epub 2020 Dec 18 doi: 10.1111/bjh.17269. PMID: 33336808
Juvenile-onset Behçet's syndrome and mimics.
Pain CE
Clin Immunol 2020 May;214:108381. Epub 2020 Mar 10 doi: 10.1016/j.clim.2020.108381. PMID: 32165216
Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment.
Meyts I, Aksentijevich I
J Clin Immunol 2018 Jul;38(5):569-578. Epub 2018 Jun 27 doi: 10.1007/s10875-018-0525-8. PMID: 29951947Free PMC Article
Adenosine deaminase deficiency.
Hirschhorn R
Immunodefic Rev 1990;2(3):175-98. PMID: 2078332

Diagnosis

Polyarteritis nodosa.
Bilginer Y, Ozen S
Curr Opin Pediatr 2022 Apr 1;34(2):229-233. doi: 10.1097/MOP.0000000000001106. PMID: 35081554
Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India.
Sharma A, Naidu G, Sharma V, Jha S, Dhooria A, Dhir V, Bhatia P, Sharma V, Bhattad S, Chengappa KG, Gupta V, Misra DP, Chavan PP, Malaviya S, Dudam R, Sharma B, Kumar S, Bhojwani R, Gupta P, Agarwal V, Sharma K, Singhal M, Rathi M, Nada R, Minz RW, Chaturvedi V, Aggarwal A, Handa R, Grossi A, Gattorno M, Huang Z, Wang J, Jois R, Negi VS, Khubchandani R, Jain S, Arostegui JI, Chambers EP, Hershfield MS, Aksentijevich I, Zhou Q, Lee PY
Arthritis Rheumatol 2021 Feb;73(2):276-285. Epub 2020 Dec 26 doi: 10.1002/art.41500. PMID: 32892503Free PMC Article
Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment.
Meyts I, Aksentijevich I
J Clin Immunol 2018 Jul;38(5):569-578. Epub 2018 Jun 27 doi: 10.1007/s10875-018-0525-8. PMID: 29951947Free PMC Article
Adenosine deaminase deficiency: a review.
Flinn AM, Gennery AR
Orphanet J Rare Dis 2018 Apr 24;13(1):65. doi: 10.1186/s13023-018-0807-5. PMID: 29690908Free PMC Article
Actionable diagnosis of neuroleptospirosis by next-generation sequencing.
Wilson MR, Naccache SN, Samayoa E, Biagtan M, Bashir H, Yu G, Salamat SM, Somasekar S, Federman S, Miller S, Sokolic R, Garabedian E, Candotti F, Buckley RH, Reed KD, Meyer TL, Seroogy CM, Galloway R, Henderson SL, Gern JE, DeRisi JL, Chiu CY
N Engl J Med 2014 Jun 19;370(25):2408-17. Epub 2014 Jun 4 doi: 10.1056/NEJMoa1401268. PMID: 24896819Free PMC Article

Therapy

Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency.
Kohn DB, Booth C, Shaw KL, Xu-Bayford J, Garabedian E, Trevisan V, Carbonaro-Sarracino DA, Soni K, Terrazas D, Snell K, Ikeda A, Leon-Rico D, Moore TB, Buckland KF, Shah AJ, Gilmour KC, De Oliveira S, Rivat C, Crooks GM, Izotova N, Tse J, Adams S, Shupien S, Ricketts H, Davila A, Uzowuru C, Icreverzi A, Barman P, Campo Fernandez B, Hollis RP, Coronel M, Yu A, Chun KM, Casas CE, Zhang R, Arduini S, Lynn F, Kudari M, Spezzi A, Zahn M, Heimke R, Labik I, Parrott R, Buckley RH, Reeves L, Cornetta K, Sokolic R, Hershfield M, Schmidt M, Candotti F, Malech HL, Thrasher AJ, Gaspar HB
N Engl J Med 2021 May 27;384(21):2002-2013. Epub 2021 May 11 doi: 10.1056/NEJMoa2027675. PMID: 33974366Free PMC Article
Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India.
Sharma A, Naidu G, Sharma V, Jha S, Dhooria A, Dhir V, Bhatia P, Sharma V, Bhattad S, Chengappa KG, Gupta V, Misra DP, Chavan PP, Malaviya S, Dudam R, Sharma B, Kumar S, Bhojwani R, Gupta P, Agarwal V, Sharma K, Singhal M, Rathi M, Nada R, Minz RW, Chaturvedi V, Aggarwal A, Handa R, Grossi A, Gattorno M, Huang Z, Wang J, Jois R, Negi VS, Khubchandani R, Jain S, Arostegui JI, Chambers EP, Hershfield MS, Aksentijevich I, Zhou Q, Lee PY
Arthritis Rheumatol 2021 Feb;73(2):276-285. Epub 2020 Dec 26 doi: 10.1002/art.41500. PMID: 32892503Free PMC Article
Epigenetic therapy induces transcription of inverted SINEs and ADAR1 dependency.
Mehdipour P, Marhon SA, Ettayebi I, Chakravarthy A, Hosseini A, Wang Y, de Castro FA, Loo Yau H, Ishak C, Abelson S, O'Brien CA, De Carvalho DD
Nature 2020 Dec;588(7836):169-173. Epub 2020 Oct 21 doi: 10.1038/s41586-020-2844-1. PMID: 33087935
Gene therapy for severe combined immunodeficiencies and beyond.
Fischer A, Hacein-Bey-Abina S
J Exp Med 2020 Jan 6;217(2) doi: 10.1084/jem.20190607. PMID: 31826240Free PMC Article
Evolving Gene Therapy in Primary Immunodeficiency.
Thrasher AJ, Williams DA
Mol Ther 2017 May 3;25(5):1132-1141. Epub 2017 Mar 31 doi: 10.1016/j.ymthe.2017.03.018. PMID: 28366768Free PMC Article

Prognosis

Severe combined immunodeficiency diagnosis and genetic defects.
Aranda CS, Gouveia-Pereira MP, da Silva CJM, Rizzo MCFV, Ishizuka E, de Oliveira EB, Condino-Neto A
Immunol Rev 2024 Mar;322(1):138-147. Epub 2024 Jan 29 doi: 10.1111/imr.13310. PMID: 38287514
Polyarteritis nodosa.
Bilginer Y, Ozen S
Curr Opin Pediatr 2022 Apr 1;34(2):229-233. doi: 10.1097/MOP.0000000000001106. PMID: 35081554
Diagnosis and management of ADA2 deficient polyarteritis nodosa.
Human A, Pagnoux C
Int J Rheum Dis 2019 Jan;22 Suppl 1:69-77. Epub 2018 Apr 6 doi: 10.1111/1756-185X.13283. PMID: 29624883
Early-onset stroke and vasculopathy associated with mutations in ADA2.
Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, Stone DL, Chae JJ, Rosenzweig SD, Bishop K, Barron KS, Kuehn HS, Hoffmann P, Negro A, Tsai WL, Cowen EW, Pei W, Milner JD, Silvin C, Heller T, Chin DT, Patronas NJ, Barber JS, Lee CC, Wood GM, Ling A, Kelly SJ, Kleiner DE, Mullikin JC, Ganson NJ, Kong HH, Hambleton S, Candotti F, Quezado MM, Calvo KR, Alao H, Barham BK, Jones A, Meschia JF, Worrall BB, Kasner SE, Rich SS, Goldbach-Mansky R, Abinun M, Chalom E, Gotte AC, Punaro M, Pascual V, Verbsky JW, Torgerson TR, Singer NG, Gershon TR, Ozen S, Karadag O, Fleisher TA, Remmers EF, Burgess SM, Moir SL, Gadina M, Sood R, Hershfield MS, Boehm M, Kastner DL, Aksentijevich I
N Engl J Med 2014 Mar 6;370(10):911-20. Epub 2014 Feb 19 doi: 10.1056/NEJMoa1307361. PMID: 24552284Free PMC Article
History of gene therapy.
Wirth T, Parker N, Ylä-Herttuala S
Gene 2013 Aug 10;525(2):162-9. Epub 2013 Apr 23 doi: 10.1016/j.gene.2013.03.137. PMID: 23618815

Clinical prediction guides

Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency.
Migliavacca M, Barzaghi F, Fossati C, Rancoita PMV, Gabaldo M, Dionisio F, Giannelli S, Salerio FA, Ferrua F, Tucci F, Calbi V, Gallo V, Recupero S, Consiglieri G, Pajno R, Sambuco M, Priolo A, Ferri C, Garella V, Monti I, Silvani P, Darin S, Casiraghi M, Corti A, Zancan S, Levi M, Cesana D, Carlucci F, Pituch-Noworolska A, AbdElaziz D, Baumann U, Finocchi A, Cancrini C, Ladogana S, Meinhardt A, Meyts I, Montin D, Notarangelo LD, Porta F, Pasquet M, Speckmann C, Stepensky P, Tommasini A, Rabusin M, Karakas Z, Galicchio M, Leonardi L, Duse M, Guner SN, Di Serio C, Ciceri F, Bernardo ME, Aiuti A, Cicalese MP
Nat Med 2024 Feb;30(2):488-497. Epub 2024 Feb 14 doi: 10.1038/s41591-023-02789-4. PMID: 38355973Free PMC Article
Gene therapy for severe combined immunodeficiencies and beyond.
Fischer A, Hacein-Bey-Abina S
J Exp Med 2020 Jan 6;217(2) doi: 10.1084/jem.20190607. PMID: 31826240Free PMC Article
Diagnosis and management of ADA2 deficient polyarteritis nodosa.
Human A, Pagnoux C
Int J Rheum Dis 2019 Jan;22 Suppl 1:69-77. Epub 2018 Apr 6 doi: 10.1111/1756-185X.13283. PMID: 29624883
Early-onset stroke and vasculopathy associated with mutations in ADA2.
Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, Stone DL, Chae JJ, Rosenzweig SD, Bishop K, Barron KS, Kuehn HS, Hoffmann P, Negro A, Tsai WL, Cowen EW, Pei W, Milner JD, Silvin C, Heller T, Chin DT, Patronas NJ, Barber JS, Lee CC, Wood GM, Ling A, Kelly SJ, Kleiner DE, Mullikin JC, Ganson NJ, Kong HH, Hambleton S, Candotti F, Quezado MM, Calvo KR, Alao H, Barham BK, Jones A, Meschia JF, Worrall BB, Kasner SE, Rich SS, Goldbach-Mansky R, Abinun M, Chalom E, Gotte AC, Punaro M, Pascual V, Verbsky JW, Torgerson TR, Singer NG, Gershon TR, Ozen S, Karadag O, Fleisher TA, Remmers EF, Burgess SM, Moir SL, Gadina M, Sood R, Hershfield MS, Boehm M, Kastner DL, Aksentijevich I
N Engl J Med 2014 Mar 6;370(10):911-20. Epub 2014 Feb 19 doi: 10.1056/NEJMoa1307361. PMID: 24552284Free PMC Article
The role of de novo purine synthesis in lymphocyte transformation.
Allison AC, Hovi T, Watts RW, Webster AD
Ciba Found Symp 1977;(48):207-24. doi: 10.1002/9780470720301.ch13. PMID: 415850

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