Identification of lysosomal and extralysosomal globotriaosylceramide (Gb3) accumulations before the occurrence of typical pathological changes in the endomyocardial biopsies of Fabry disease patients

Ming Jia Hsu, Fu Pang Chang, Yung Hsiu Lu, Sheng Che Hung, Yu Chen Wang, An Hang Yang, Han Jui Lee, Shih Hsien Sung, Yen Feng Wang, Wen Chung Yu, Ting Rong Hsu, Po Hsun Huang, Sheng Kai Chang, Ivan Dzhagalov, Chia Lin Hsu*, Dau Ming Niu

*此作品的通信作者

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

Purpose: Evaluation standards and treatment initiation timing have been debated for a long time, particularly for late-onset Fabry disease (FD), because of its slow progression. However, early initiation of enzyme replacement therapy (ERT) for FD could be effective in stabilizing the disease progression and potentially preventing irreversible organ damage. We aimed to examine globotriaosylceramide (Gb3) deposits in patients’ endomyocardial biopsies to understand the early pathogenesis of FD cardiomyopathy. Methods: Immunofluorescent (IF) staining of Gb3 and lysosomal-associated membrane protein 1 (LAMP-1) was performed on endomyocardial biopsies of patients suspected of Fabry cardiomyopathy who had negative or only slight Gb3 accumulation determined by toluidine blue staining and electron microscopic examination. Results: The IF staining results revealed that all patients examined had abundant Gb3 accumulation in their cardiomyocytes, including the ones who are negative for inclusion bodies. Furthermore, we found that early Gb3 deposits were mostly confined within lysosomes, while they appeared extralysosomally at a later stage. Conclusion: A significant amount of lysosomal Gb3 deposits could be detected by IF staining in cardiac tissue before the formation of inclusion bodies, suggesting the cardiomyocytes might have been experiencing cellular stress and damage early on, before the appearance of typical pathological changes of FD during the disease progression.

原文English
頁(從 - 到)224-232
頁數9
期刊Genetics in Medicine
21
發行號1
DOIs
出版狀態Published - 1 1月 2019

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