2024 Update of the TSOC Expert Consensus of Fabry Disease.
Journal
Acta Cardiologica Sinica
Journal Volume
40
Journal Issue
5
Pages
544-568
ISSN
1011-6842
Date Issued
2024-09
Author(s)
Hung, Chung-Lieh
Kuo, Ling
Sung, Kuo-Tzu
Lin, Heng-Hsu
Chang, Wei-Ting
Chang, Chia-Hsiu
Lai, Chih-Hung
Huang, Chun-Yao
Wang, Chun-Li
Lin, Chih-Chan
Juang, Jyh-Ming Jimmy
Chen, Po-Sheng
Wang, Chao-Yung
Chang, Hao-Chih
Chu, Chun-Yuan
Wang, Wen-Hwa
Tseng, Hsinyu
Kao, Yung-Ta
Yu, Wen-Chung
Abstract
As an X-linked inherited lysosomal storage disease that is caused by α-galactosidase A gene variants resulting in progressive accumulation of pathogenic glycosphingolipid (Gb3) accumulation in multiple tissues and organs, Fabry disease (FD) can be classified into classic or late-onset phenotypes. In classic phenotype patients, α-galactosidase A activity is absent or severely reduced, resulting in a more progressive disease course with multi-systemic involvement. Conversely, late-onset phenotype, often with missense variants (e.g., IVS4+919G>A) in Taiwan, may present with a more chronic clinical course with predominant cardiac involvement (cardiac subtype), as they tend to have residual enzyme activity, remaining asymptomatic or clinically silent during childhood and adolescence. In either form, cardiac hypertrophy remains the most common feature of cardiac involvement, potentially leading to myocardial fibrosis, arrhythmias, and heart failure. Diagnosis is established through α-galactosidase enzyme activity assessment or biomarker analyisis (globotriaosylsphingosine, Lyso-Gb3), advanced imaging modalities (echocardiography and cardiac magnetic resonance imaging), and genotyping to differentiate FD from other cardiomyopathy. Successful therapeutic response relies on early recognition and by disease awareness from typical features in classic phenotype and cardiac red flags in cardiac variants for timely therapeutic interventions. Recent advances in pharmacological approach including enzyme replacement therapy (agalsidase alfa or beta), oral chaperone therapy (migalastat), and substrate reduction therapy (venglustat) aim to prevent from irreversible organ damage. Genotype- and gender-based monitoring of treatment effects through biomarker (Lyso-Gb3), renal assessment, and cardiac responses using advanced imaging modalities are key steps to optimizing patient care in FD.
Subjects
Cardiac variant
Chaperone
Enzyme replacement therapy
Fabry disease
Globotriaosylceramide
Globotriaosylsphingosine
Heart failure with preserved ejection fraction
IVS4+919G>A
Left ventricular hypertrophy
α-galactosidase A gene
SDGs
Type
journal article