2024 Update of the TSOC Expert Consensus of Fabry Disease

10.6515/ACS.202409_40(5).20240731A

Chung-Lieh Hung；Yen-Wen Wu；Ling Kuo；Kuo-Tzu Sung；Heng-Hsu Lin；Wei-Ting Chang；Chia-Hsiu Chang；Chih-Hung Lai；Chun-Yao Huang；Chun-Li Wang；Chih-Chan Lin；Jyh-Ming Jimmy Juang；Po-Sheng Chen；Chao-Yung Wang；Hao-Chih Chang；Chun-Yuan Chu；Wen-Hwa Wang；Hsinyu Tseng；Yung-Ta Kao；Tzung-Dau Wang；Wen-Chung Yu；Wen-Jone Chen

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

Acta Cardiologica Sinica

40卷5期（2024 / 09 / 01）

544 - 568

英文

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 chronicclinical 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.