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Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies

BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors a...

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Autores principales: D’Amico, Adele, Longo, Antonella, Fattori, Fabiana, Tosi, Michele, Bosco, Luca, Chiarini Testa, Maria Beatrice, Paglietti, Maria Giovanna, Cherchi, Claudio, Carlesi, Adelina, Mizzoni, Irene, Bertini, Enrico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513353/
https://www.ncbi.nlm.nih.gov/pubmed/34641930
http://dx.doi.org/10.1186/s13023-021-02055-1
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author D’Amico, Adele
Longo, Antonella
Fattori, Fabiana
Tosi, Michele
Bosco, Luca
Chiarini Testa, Maria Beatrice
Paglietti, Maria Giovanna
Cherchi, Claudio
Carlesi, Adelina
Mizzoni, Irene
Bertini, Enrico
author_facet D’Amico, Adele
Longo, Antonella
Fattori, Fabiana
Tosi, Michele
Bosco, Luca
Chiarini Testa, Maria Beatrice
Paglietti, Maria Giovanna
Cherchi, Claudio
Carlesi, Adelina
Mizzoni, Irene
Bertini, Enrico
author_sort D’Amico, Adele
collection PubMed
description BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors are often non-ambulant, ventilator and feeding tube–dependent and they generally show additional organ manifestations, indicating that myotubularin does play a vital role in tissues other than muscle. For XLMTM several therapeutic strategies are under investigation. For XLMTM several therapeutic strategies are under investigation including a study of intravenous MTM1 gene transfer using a recombinant AAV8 vector of which has some concerns arises due to hepatotoxicity. RESULTS: We report prospective and retrospective clinical data of 12 XLMTM patients collected over a period of up to 10 years. In particular, we carried out a thorough review of the data about incidence and the course of hepatobiliary disease in our case series. CONCLUSIONS: We demonstrate that hepatobiliary disease represents a common comorbidity of XLMTM that seems irrespective to age and diseases severity. We recommend to carefully explore and monitor the hepatobiliary function in XLMTM patients. We believe that a better understanding of the pathogenic mechanisms that induce hepatobiliary damage is essential to understand the fatal events that may occur in the gene therapy program.
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spelling pubmed-85133532021-10-20 Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies D’Amico, Adele Longo, Antonella Fattori, Fabiana Tosi, Michele Bosco, Luca Chiarini Testa, Maria Beatrice Paglietti, Maria Giovanna Cherchi, Claudio Carlesi, Adelina Mizzoni, Irene Bertini, Enrico Orphanet J Rare Dis Research BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors are often non-ambulant, ventilator and feeding tube–dependent and they generally show additional organ manifestations, indicating that myotubularin does play a vital role in tissues other than muscle. For XLMTM several therapeutic strategies are under investigation. For XLMTM several therapeutic strategies are under investigation including a study of intravenous MTM1 gene transfer using a recombinant AAV8 vector of which has some concerns arises due to hepatotoxicity. RESULTS: We report prospective and retrospective clinical data of 12 XLMTM patients collected over a period of up to 10 years. In particular, we carried out a thorough review of the data about incidence and the course of hepatobiliary disease in our case series. CONCLUSIONS: We demonstrate that hepatobiliary disease represents a common comorbidity of XLMTM that seems irrespective to age and diseases severity. We recommend to carefully explore and monitor the hepatobiliary function in XLMTM patients. We believe that a better understanding of the pathogenic mechanisms that induce hepatobiliary damage is essential to understand the fatal events that may occur in the gene therapy program. BioMed Central 2021-10-12 /pmc/articles/PMC8513353/ /pubmed/34641930 http://dx.doi.org/10.1186/s13023-021-02055-1 Text en © The Author(s) 2021, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
D’Amico, Adele
Longo, Antonella
Fattori, Fabiana
Tosi, Michele
Bosco, Luca
Chiarini Testa, Maria Beatrice
Paglietti, Maria Giovanna
Cherchi, Claudio
Carlesi, Adelina
Mizzoni, Irene
Bertini, Enrico
Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies
title Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies
title_full Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies
title_fullStr Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies
title_full_unstemmed Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies
title_short Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies
title_sort hepatobiliary disease in xlmtm: a common comorbidity with potential impact on treatment strategies
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513353/
https://www.ncbi.nlm.nih.gov/pubmed/34641930
http://dx.doi.org/10.1186/s13023-021-02055-1
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