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The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited
Deficiency of Adenosine Deaminase Type 2 (DADA2) is a rare autosomal recessive inherited disorder with a variable phenotype including generalized or cerebral vasculitis and bone marrow failure. It is caused by variations in the adenosine deaminase 2 gene (ADA2), which leads to decreased adenosine de...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237362/ https://www.ncbi.nlm.nih.gov/pubmed/35774100 http://dx.doi.org/10.3389/fped.2022.885893 |
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author | Escherich, Carolin Bötticher, Benedikt Harmsen, Stefani Hömberg, Marc Schaper, Jörg Lorenz, Myriam Ricarda Schwarz, Klaus Borkhardt, Arndt Oommen, Prasad Thomas |
author_facet | Escherich, Carolin Bötticher, Benedikt Harmsen, Stefani Hömberg, Marc Schaper, Jörg Lorenz, Myriam Ricarda Schwarz, Klaus Borkhardt, Arndt Oommen, Prasad Thomas |
author_sort | Escherich, Carolin |
collection | PubMed |
description | Deficiency of Adenosine Deaminase Type 2 (DADA2) is a rare autosomal recessive inherited disorder with a variable phenotype including generalized or cerebral vasculitis and bone marrow failure. It is caused by variations in the adenosine deaminase 2 gene (ADA2), which leads to decreased adenosine deaminase 2 enzyme activity. Here we present three instructive scenarios that demonstrate DADA2 spectrum characteristics and provide a clear and thorough diagnostic and therapeutic workflow for effective patient care. Patient 1 illustrates cerebral vasculitis in DADA2. Genetic analysis reveals a compound heterozygosity including the novel ADA2 variant, p.V325Tfs(*)7. In patient 2, different vasculitis phenotypes of the DADA2 spectrum are presented, all resulting from the homozygous ADA2 mutation p.Y453C. In this family, the potential risk for siblings is particularly evident. Patient 3 represents pure red cell aplasia with bone marrow failure in DADA2. Here, ultimately, stem cell transplantation is considered the curative treatment option. The diversity of the DADA2 spectrum often delays diagnosis and treatment of this vulnerable patient cohort. We therefore recommend early ADA2 enzyme activity measurement as a screening tool for patients and siblings at risk, and we expect early steroid-based remission induction will help avoid fatal outcomes. |
format | Online Article Text |
id | pubmed-9237362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92373622022-06-29 The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited Escherich, Carolin Bötticher, Benedikt Harmsen, Stefani Hömberg, Marc Schaper, Jörg Lorenz, Myriam Ricarda Schwarz, Klaus Borkhardt, Arndt Oommen, Prasad Thomas Front Pediatr Pediatrics Deficiency of Adenosine Deaminase Type 2 (DADA2) is a rare autosomal recessive inherited disorder with a variable phenotype including generalized or cerebral vasculitis and bone marrow failure. It is caused by variations in the adenosine deaminase 2 gene (ADA2), which leads to decreased adenosine deaminase 2 enzyme activity. Here we present three instructive scenarios that demonstrate DADA2 spectrum characteristics and provide a clear and thorough diagnostic and therapeutic workflow for effective patient care. Patient 1 illustrates cerebral vasculitis in DADA2. Genetic analysis reveals a compound heterozygosity including the novel ADA2 variant, p.V325Tfs(*)7. In patient 2, different vasculitis phenotypes of the DADA2 spectrum are presented, all resulting from the homozygous ADA2 mutation p.Y453C. In this family, the potential risk for siblings is particularly evident. Patient 3 represents pure red cell aplasia with bone marrow failure in DADA2. Here, ultimately, stem cell transplantation is considered the curative treatment option. The diversity of the DADA2 spectrum often delays diagnosis and treatment of this vulnerable patient cohort. We therefore recommend early ADA2 enzyme activity measurement as a screening tool for patients and siblings at risk, and we expect early steroid-based remission induction will help avoid fatal outcomes. Frontiers Media S.A. 2022-06-14 /pmc/articles/PMC9237362/ /pubmed/35774100 http://dx.doi.org/10.3389/fped.2022.885893 Text en Copyright © 2022 Escherich, Bötticher, Harmsen, Hömberg, Schaper, Lorenz, Schwarz, Borkhardt and Oommen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Escherich, Carolin Bötticher, Benedikt Harmsen, Stefani Hömberg, Marc Schaper, Jörg Lorenz, Myriam Ricarda Schwarz, Klaus Borkhardt, Arndt Oommen, Prasad Thomas The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited |
title | The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited |
title_full | The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited |
title_fullStr | The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited |
title_full_unstemmed | The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited |
title_short | The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited |
title_sort | growing spectrum of dada2 manifestations—diagnostic and therapeutic challenges revisited |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237362/ https://www.ncbi.nlm.nih.gov/pubmed/35774100 http://dx.doi.org/10.3389/fped.2022.885893 |
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