ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation
Adenosine deaminase 2 (ADA2) deficiency is an auto-inflammatory disease due to mutations in cat eye syndrome chromosome region candidate 1 (CECR1) gene, currently named ADA2. The disease has a wide clinical spectrum encompassing early-onset vasculopathy (targeting skin, gut and central nervous syste...
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Frontiers Media S.A.
2019-01-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02767/full |
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doaj-47f65f0e0e954a7a959df3bccfcbee78 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Federica Barzaghi Federica Barzaghi Federica Barzaghi Federica Minniti Margherita Mauro Massimiliano De Bortoli Rita Balter Elisa Bonetti Ada Zaccaron Virginia Vitale Maryam Omrani Matteo Zoccolillo Matteo Zoccolillo Immacolata Brigida Maria Pia Cicalese Maria Pia Cicalese Massimo Degano Michael S. Hershfield Alessandro Aiuti Alessandro Aiuti Alessandro Aiuti Anastasiia V. Bondarenko Matteo Chinello Simone Cesaro |
spellingShingle |
Federica Barzaghi Federica Barzaghi Federica Barzaghi Federica Minniti Margherita Mauro Massimiliano De Bortoli Rita Balter Elisa Bonetti Ada Zaccaron Virginia Vitale Maryam Omrani Matteo Zoccolillo Matteo Zoccolillo Immacolata Brigida Maria Pia Cicalese Maria Pia Cicalese Massimo Degano Michael S. Hershfield Alessandro Aiuti Alessandro Aiuti Alessandro Aiuti Anastasiia V. Bondarenko Matteo Chinello Simone Cesaro ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation Frontiers in Immunology ADA2 deficiency HSCT ALPS ADA2 CECR1 autoimmunity |
author_facet |
Federica Barzaghi Federica Barzaghi Federica Barzaghi Federica Minniti Margherita Mauro Massimiliano De Bortoli Rita Balter Elisa Bonetti Ada Zaccaron Virginia Vitale Maryam Omrani Matteo Zoccolillo Matteo Zoccolillo Immacolata Brigida Maria Pia Cicalese Maria Pia Cicalese Massimo Degano Michael S. Hershfield Alessandro Aiuti Alessandro Aiuti Alessandro Aiuti Anastasiia V. Bondarenko Matteo Chinello Simone Cesaro |
author_sort |
Federica Barzaghi |
title |
ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation |
title_short |
ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation |
title_full |
ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation |
title_fullStr |
ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation |
title_full_unstemmed |
ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation |
title_sort |
alps-like phenotype caused by ada2 deficiency rescued by allogeneic hematopoietic stem cell transplantation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-01-01 |
description |
Adenosine deaminase 2 (ADA2) deficiency is an auto-inflammatory disease due to mutations in cat eye syndrome chromosome region candidate 1 (CECR1) gene, currently named ADA2. The disease has a wide clinical spectrum encompassing early-onset vasculopathy (targeting skin, gut and central nervous system), recurrent fever, immunodeficiency and bone marrow dysfunction. Different therapeutic options have been proposed in literature, but only steroids and anti-cytokine monoclonal antibodies (such as tumor necrosis factor inhibitor) proved to be effective. If a suitable donor is available, hematopoietic stem cell transplantation (HSCT) could be curative. Here we describe a case of ADA2 deficiency in a 4-year-old Caucasian girl. The patient was initially classified as autoimmune neutropenia and then she evolved toward an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. The diagnosis of ALPS became uncertain due to atypical clinical features and normal FAS-induced apoptosis test. She was treated with G-CSF first and subsequently with immunosuppressive drugs without improvement. Only HSCT from a 9/10 HLA-matched unrelated donor, following myeloablative conditioning, completely solved the clinical signs related to ADA2 deficiency. Early diagnosis in cases presenting with hematological manifestations, rather than classical vasculopathy, allows the patients to promptly undergo HSCT and avoid more severe evolution. Finally, in similar cases highly suspicious for genetic disease, it is desirable to obtain molecular diagnosis before performing HSCT, since it can influence the transplant procedure. However, if HSCT has to be performed without delay for clinical indication, related donors should be excluded to avoid the risk of relapse or partial benefit due to a hereditary genetic defect. |
topic |
ADA2 deficiency HSCT ALPS ADA2 CECR1 autoimmunity |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.02767/full |
work_keys_str_mv |
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doaj-47f65f0e0e954a7a959df3bccfcbee782020-11-25T00:49:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-01-01910.3389/fimmu.2018.02767418879ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell TransplantationFederica Barzaghi0Federica Barzaghi1Federica Barzaghi2Federica Minniti3Margherita Mauro4Massimiliano De Bortoli5Rita Balter6Elisa Bonetti7Ada Zaccaron8Virginia Vitale9Maryam Omrani10Matteo Zoccolillo11Matteo Zoccolillo12Immacolata Brigida13Maria Pia Cicalese14Maria Pia Cicalese15Massimo Degano16Michael S. Hershfield17Alessandro Aiuti18Alessandro Aiuti19Alessandro Aiuti20Anastasiia V. Bondarenko21Matteo Chinello22Simone Cesaro23Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalySan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, ItalyDepartment of Systems Medicine, Tor Vergata University, >Rome, ItalyPaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalyPaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalyPaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalyPaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalyPaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalyPaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalyPaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalySan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, ItalySan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, ItalyDepartment of Systems Medicine, Tor Vergata University, >Rome, ItalySan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, ItalyPediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalySan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, ItalyBiocrystallography Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, ItalyDepartment of Medicine and Biochemistry, Duke University School of Medicine, Durham, NC, United StatesPediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalySan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyDepartment of Pediatric Infectious Diseases and Immunology, Medical Academy of Postgraduate Education, Kiev, UkrainePaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalyPaediatric Hematology-Oncology, Ospedale della Donna e del Bambino, Verona, ItalyAdenosine deaminase 2 (ADA2) deficiency is an auto-inflammatory disease due to mutations in cat eye syndrome chromosome region candidate 1 (CECR1) gene, currently named ADA2. The disease has a wide clinical spectrum encompassing early-onset vasculopathy (targeting skin, gut and central nervous system), recurrent fever, immunodeficiency and bone marrow dysfunction. Different therapeutic options have been proposed in literature, but only steroids and anti-cytokine monoclonal antibodies (such as tumor necrosis factor inhibitor) proved to be effective. If a suitable donor is available, hematopoietic stem cell transplantation (HSCT) could be curative. Here we describe a case of ADA2 deficiency in a 4-year-old Caucasian girl. The patient was initially classified as autoimmune neutropenia and then she evolved toward an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. The diagnosis of ALPS became uncertain due to atypical clinical features and normal FAS-induced apoptosis test. She was treated with G-CSF first and subsequently with immunosuppressive drugs without improvement. Only HSCT from a 9/10 HLA-matched unrelated donor, following myeloablative conditioning, completely solved the clinical signs related to ADA2 deficiency. Early diagnosis in cases presenting with hematological manifestations, rather than classical vasculopathy, allows the patients to promptly undergo HSCT and avoid more severe evolution. Finally, in similar cases highly suspicious for genetic disease, it is desirable to obtain molecular diagnosis before performing HSCT, since it can influence the transplant procedure. However, if HSCT has to be performed without delay for clinical indication, related donors should be excluded to avoid the risk of relapse or partial benefit due to a hereditary genetic defect.https://www.frontiersin.org/article/10.3389/fimmu.2018.02767/fullADA2 deficiencyHSCTALPSADA2CECR1autoimmunity |