Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement

Pui Y. Lee; Brad A. Davidson; Roshini S. Abraham; Blanche Alter; Juan I. Arostegui; Katherine Bell; Alexandre Belot; Jenna R.E. Bergerson; Timothy J. Bernard; Paul A. Brogan; Yackov Berkun; Natalie T. Deuitch; Dimana Dimitrova; Sophie A. Georgin-Lavialle; Marco Gattorno; Bodo Grimbacher; Hasan Hashem; Michael S. Hershfield; Rebecca N. Ichord; Kazushi Izawa; Jennifer A. Kanakry; Raju P. Khubchandani; Femke C.C. Klouwer; Evan A. Luton; Ada W. Man; Isabelle Meyts; Joris M. Van Montfrans; Seza Ozen; Janna Saarela; Gustavo C. Santo; Aman Sharma; Ariane Soldatos; Rachel Sparks; Troy R. Torgerson; Ignacio Leandro Uriarte; Taryn A.B. Youngstein; Qing Zhou; Ivona Aksentijevich; Daniel L. Kastner; Eugene P. Chambers; Amanda K. Ombrello

doi:10.1001/jamanetworkopen.2023.15894

Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement

Pui Y. Lee^*
, Brad A. Davidson
, Roshini S. Abraham
, Blanche Alter
, Juan I. Arostegui
, Katherine Bell
, Alexandre Belot
, Jenna R.E. Bergerson
, Timothy J. Bernard
, Paul A. Brogan
, Yackov Berkun
, Natalie T. Deuitch
, Dimana Dimitrova
, Sophie A. Georgin-Lavialle
, Marco Gattorno
, Bodo Grimbacher
, Hasan Hashem
, Michael S. Hershfield
, Rebecca N. Ichord
, Kazushi Izawa

Jennifer A. Kanakry, Raju P. Khubchandani, Femke C.C. Klouwer, Evan A. Luton, Ada W. Man, Isabelle Meyts, Joris M. Van Montfrans, Seza Ozen, Janna Saarela, Gustavo C. Santo, Aman Sharma, Ariane Soldatos, Rachel Sparks, Troy R. Torgerson, Ignacio Leandro Uriarte, Taryn A.B. Youngstein, Qing Zhou, Ivona Aksentijevich, Daniel L. Kastner, Eugene P. Chambers, Amanda K. Ombrello^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Importance: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more common monogenic autoinflammatory diseases, with an estimate of more than 35000 cases worldwide, but currently, there are no guidelines for diagnostic evaluation or management. Objective: To review the available evidence and develop multidisciplinary consensus statements for the evaluation and management of DADA2. Evidence Review: The DADA2 Consensus Committee developed research questions based on data collected from the International Meetings on DADA2 organized by the DADA2 Foundation in 2016, 2018, and 2020. A comprehensive literature review was performed for articles published prior to 2022. Thirty-two consensus statements were generated using a modified Delphi process, and evidence was graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence. Findings: The DADA2 Consensus Committee, comprising 3 patient representatives and 35 international experts from 18 countries, developed consensus statements for (1) diagnostic testing, (2) screening, (3) clinical and laboratory evaluation, and (4) management of DADA2 based on disease phenotype. Additional consensus statements related to the evaluation and treatment of individuals with DADA2 who are presymptomatic and carriers were generated. Areas with insufficient evidence were identified, and questions for future research were outlined. Conclusions and Relevance: DADA2 is a potentially fatal disease that requires early diagnosis and treatment. By summarizing key evidence and expert opinions, these consensus statements provide a framework to facilitate diagnostic evaluation and management of DADA2.

Original language	English
Article number	e2315894
Journal	JAMA network open
Volume	6
Issue number	5
DOIs	https://doi.org/10.1001/jamanetworkopen.2023.15894
Publication status	Published - 31 May 2023

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lee_2023_cs_230003_1684514579.32894Final published version, 859 KBLicence: CC BY

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Lee, P. Y., Davidson, B. A., Abraham, R. S., Alter, B., Arostegui, J. I., Bell, K., Belot, A., Bergerson, J. R. E., Bernard, T. J., Brogan, P. A., Berkun, Y., Deuitch, N. T., Dimitrova, D., Georgin-Lavialle, S. A., Gattorno, M., Grimbacher, B., Hashem, H., Hershfield, M. S., Ichord, R. N., ... Ombrello, A. K. (2023). Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement. JAMA network open, 6(5), Article e2315894. https://doi.org/10.1001/jamanetworkopen.2023.15894

@article{e6c862ff6b5d46e59fc77491401525d2,

title = "Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement",

abstract = "Importance: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more common monogenic autoinflammatory diseases, with an estimate of more than 35000 cases worldwide, but currently, there are no guidelines for diagnostic evaluation or management. Objective: To review the available evidence and develop multidisciplinary consensus statements for the evaluation and management of DADA2. Evidence Review: The DADA2 Consensus Committee developed research questions based on data collected from the International Meetings on DADA2 organized by the DADA2 Foundation in 2016, 2018, and 2020. A comprehensive literature review was performed for articles published prior to 2022. Thirty-two consensus statements were generated using a modified Delphi process, and evidence was graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence. Findings: The DADA2 Consensus Committee, comprising 3 patient representatives and 35 international experts from 18 countries, developed consensus statements for (1) diagnostic testing, (2) screening, (3) clinical and laboratory evaluation, and (4) management of DADA2 based on disease phenotype. Additional consensus statements related to the evaluation and treatment of individuals with DADA2 who are presymptomatic and carriers were generated. Areas with insufficient evidence were identified, and questions for future research were outlined. Conclusions and Relevance: DADA2 is a potentially fatal disease that requires early diagnosis and treatment. By summarizing key evidence and expert opinions, these consensus statements provide a framework to facilitate diagnostic evaluation and management of DADA2.",

author = "Lee, \{Pui Y.\} and Davidson, \{Brad A.\} and Abraham, \{Roshini S.\} and Blanche Alter and Arostegui, \{Juan I.\} and Katherine Bell and Alexandre Belot and Bergerson, \{Jenna R.E.\} and Bernard, \{Timothy J.\} and Brogan, \{Paul A.\} and Yackov Berkun and Deuitch, \{Natalie T.\} and Dimana Dimitrova and Georgin-Lavialle, \{Sophie A.\} and Marco Gattorno and Bodo Grimbacher and Hasan Hashem and Hershfield, \{Michael S.\} and Ichord, \{Rebecca N.\} and Kazushi Izawa and Kanakry, \{Jennifer A.\} and Khubchandani, \{Raju P.\} and Klouwer, \{Femke C.C.\} and Luton, \{Evan A.\} and Man, \{Ada W.\} and Isabelle Meyts and \{Van Montfrans\}, \{Joris M.\} and Seza Ozen and Janna Saarela and Santo, \{Gustavo C.\} and Aman Sharma and Ariane Soldatos and Rachel Sparks and Torgerson, \{Troy R.\} and Uriarte, \{Ignacio Leandro\} and Youngstein, \{Taryn A.B.\} and Qing Zhou and Ivona Aksentijevich and Kastner, \{Daniel L.\} and Chambers, \{Eugene P.\} and Ombrello, \{Amanda K.\}",

year = "2023",

month = may,

day = "31",

doi = "10.1001/jamanetworkopen.2023.15894",

language = "English",

volume = "6",

journal = "JAMA network open",

issn = "2574-3805",

publisher = "American Medical Association",

number = "5",

}

Lee, PY, Davidson, BA, Abraham, RS, Alter, B, Arostegui, JI, Bell, K, Belot, A, Bergerson, JRE, Bernard, TJ, Brogan, PA, Berkun, Y, Deuitch, NT, Dimitrova, D, Georgin-Lavialle, SA, Gattorno, M, Grimbacher, B, Hashem, H, Hershfield, MS, Ichord, RN, Izawa, K, Kanakry, JA, Khubchandani, RP, Klouwer, FCC, Luton, EA, Man, AW, Meyts, I, Van Montfrans, JM, Ozen, S, Saarela, J, Santo, GC, Sharma, A, Soldatos, A, Sparks, R, Torgerson, TR, Uriarte, IL, Youngstein, TAB, Zhou, Q, Aksentijevich, I, Kastner, DL, Chambers, EP & Ombrello, AK 2023, 'Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement', JAMA network open, vol. 6, no. 5, e2315894. https://doi.org/10.1001/jamanetworkopen.2023.15894

TY - JOUR

T1 - Evaluation and Management of Deficiency of Adenosine Deaminase 2

T2 - An International Consensus Statement

AU - Lee, Pui Y.

AU - Davidson, Brad A.

AU - Abraham, Roshini S.

AU - Alter, Blanche

AU - Arostegui, Juan I.

AU - Bell, Katherine

AU - Belot, Alexandre

AU - Bergerson, Jenna R.E.

AU - Bernard, Timothy J.

AU - Brogan, Paul A.

AU - Berkun, Yackov

AU - Deuitch, Natalie T.

AU - Dimitrova, Dimana

AU - Georgin-Lavialle, Sophie A.

AU - Gattorno, Marco

AU - Grimbacher, Bodo

AU - Hashem, Hasan

AU - Hershfield, Michael S.

AU - Ichord, Rebecca N.

AU - Izawa, Kazushi

AU - Kanakry, Jennifer A.

AU - Khubchandani, Raju P.

AU - Klouwer, Femke C.C.

AU - Luton, Evan A.

AU - Man, Ada W.

AU - Meyts, Isabelle

AU - Van Montfrans, Joris M.

AU - Ozen, Seza

AU - Saarela, Janna

AU - Santo, Gustavo C.

AU - Sharma, Aman

AU - Soldatos, Ariane

AU - Sparks, Rachel

AU - Torgerson, Troy R.

AU - Uriarte, Ignacio Leandro

AU - Youngstein, Taryn A.B.

AU - Zhou, Qing

AU - Aksentijevich, Ivona

AU - Kastner, Daniel L.

AU - Chambers, Eugene P.

AU - Ombrello, Amanda K.

PY - 2023/5/31

Y1 - 2023/5/31

N2 - Importance: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more common monogenic autoinflammatory diseases, with an estimate of more than 35000 cases worldwide, but currently, there are no guidelines for diagnostic evaluation or management. Objective: To review the available evidence and develop multidisciplinary consensus statements for the evaluation and management of DADA2. Evidence Review: The DADA2 Consensus Committee developed research questions based on data collected from the International Meetings on DADA2 organized by the DADA2 Foundation in 2016, 2018, and 2020. A comprehensive literature review was performed for articles published prior to 2022. Thirty-two consensus statements were generated using a modified Delphi process, and evidence was graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence. Findings: The DADA2 Consensus Committee, comprising 3 patient representatives and 35 international experts from 18 countries, developed consensus statements for (1) diagnostic testing, (2) screening, (3) clinical and laboratory evaluation, and (4) management of DADA2 based on disease phenotype. Additional consensus statements related to the evaluation and treatment of individuals with DADA2 who are presymptomatic and carriers were generated. Areas with insufficient evidence were identified, and questions for future research were outlined. Conclusions and Relevance: DADA2 is a potentially fatal disease that requires early diagnosis and treatment. By summarizing key evidence and expert opinions, these consensus statements provide a framework to facilitate diagnostic evaluation and management of DADA2.

AB - Importance: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more common monogenic autoinflammatory diseases, with an estimate of more than 35000 cases worldwide, but currently, there are no guidelines for diagnostic evaluation or management. Objective: To review the available evidence and develop multidisciplinary consensus statements for the evaluation and management of DADA2. Evidence Review: The DADA2 Consensus Committee developed research questions based on data collected from the International Meetings on DADA2 organized by the DADA2 Foundation in 2016, 2018, and 2020. A comprehensive literature review was performed for articles published prior to 2022. Thirty-two consensus statements were generated using a modified Delphi process, and evidence was graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence. Findings: The DADA2 Consensus Committee, comprising 3 patient representatives and 35 international experts from 18 countries, developed consensus statements for (1) diagnostic testing, (2) screening, (3) clinical and laboratory evaluation, and (4) management of DADA2 based on disease phenotype. Additional consensus statements related to the evaluation and treatment of individuals with DADA2 who are presymptomatic and carriers were generated. Areas with insufficient evidence were identified, and questions for future research were outlined. Conclusions and Relevance: DADA2 is a potentially fatal disease that requires early diagnosis and treatment. By summarizing key evidence and expert opinions, these consensus statements provide a framework to facilitate diagnostic evaluation and management of DADA2.

UR - https://www.scopus.com/pages/publications/85160965943

U2 - 10.1001/jamanetworkopen.2023.15894

DO - 10.1001/jamanetworkopen.2023.15894

M3 - Article

C2 - 37256629

AN - SCOPUS:85160965943

SN - 2574-3805

VL - 6

JO - JAMA network open

JF - JAMA network open

IS - 5

M1 - e2315894

ER -

Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement

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