Life-cycle management of Fabry cardiomyopathy_West China Medical Journal

Authors：

LOU Jingfeng ¹ ,  CHEN Yucheng ^1,2,3

1. Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Cardiac Imaging and Target Therapy Lab, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

CHEN Yucheng, Email: chenyucheng2003@163.com

Keywords：

Fabry disease; Fabry cardiomyopathy; life-cycle management

DOI：

10.7507/1002-0179.202512182

Video：

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Fabry disease is an X-linked lysosomal storage disorder in which cardiac involvement represents the leading cause of mortality. Despite continuous advances in diagnostic approaches, including genetic testing and cardiac imaging, delayed diagnosis and inappropriate management remain major clinical challenges, resulting in substantial impairment of quality of life and survival. Therefore, the establishment of a comprehensive, life-cycle management strategy encompassing screening, diagnosis, individualized treatment, and lifelong follow-up is essential to improve patient outcomes. In this review, we summarize recent advances in the epidemiology, genotype-phenotype correlations, diagnosis, and treatment of Fabry cardiomyopathy, and propose a novel concept for the life-cycle management of patients with Fabry cardiomyopathy.

Citation： LOU Jingfeng, CHEN Yucheng. Life-cycle management of Fabry cardiomyopathy. West China Medical Journal, 2026, 41(1): 130-135. doi: 10.7507/1002-0179.202512182 Copy

1.	Patel MR, Cecchi F, Cizmarik M, et al. Cardiovascular events in patients with Fabry disease natural history data from the Fabry registry. J Am Coll Cardiol, 2011, 57(9): 1093-1099.
2.	O’Mahony C, Elliott P. Anderson-Fabry disease and the heart. Prog Cardiovasc Dis, 2010, 52(4): 326-335.
3.	Hwu WL, Chien YH, Lee NC, et al. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c. 936+919G>A (IVS4+919G>A). Hum Mutat, 2009, 30(10): 1397-1405.
4.	Gragnaniello V, Burlina AP, Polo G, et al. Newborn screening for Fabry disease in Northeastern Italy: results of five years of experience. Biomolecules, 2021, 11(7): 951.
5.	Lv YL, Wang WM, Pan XX, et al. A successful screening for Fabry disease in a Chinese dialysis patient population. Clin Genet, 2009, 76(2): 219-221.
6.	Li J, Pu L, Xu Z, et al. Screening for Fabry disease in patients with hypertrophic cardiomyopathy using cardiac magnetic resonance imaging. Eur Radiol, 2025, 35(5): 2888-2898.
7.	Reisin R, Perrin A, García-Pavía P. Time delays in the diagnosis and treatment of Fabry disease. Int J Clin Pract, 2017, 71(1): e12914.
8.	Ortiz A, Germain DP, Desnick RJ, et al. Fabry disease revisited: management and treatment recommendations for adult patients. Mol Genet Metab, 2018, 123(4): 416-427.
9.	中國法布雷病專家協作組. 中國法布雷病診療專家共識(2021 年版). 中華內科雜志, 2021, 60(4): 321-330.
10.	Giammanco A, Gagliardo CM, Scrimali C, et al. Clinical and biochemical characterization of Fabry disease associated GLA gene variants: data from a large cohort of 469 thousand genotyped subjects of the UK Biobank Database. J Inherit Metab Dis, 2025, 48(6): e70103.
11.	Oliveira JP, Ferreira S. Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype-phenotype correlations. Appl Clin Genet, 2019, 12: 35-50.
12.	Sakuraba H, Togawa T, Tsukimura T, et al. Plasma lyso-Gb3: a biomarker for monitoring Fabry patients during enzyme replacement therapy. Clin Exp Nephrol, 2018, 22(4): 843-849.
13.	Sivley MD, Wallace EL, Warnock DG, et al. Conjunctival lymphangiectasia associated with classic Fabry disease. Br J Ophthalmol, 2018, 102(1): 54-58.
14.	Shabbeer J, Yasuda M, Luca E, et al. Fabry disease: 45 novel mutations in the alpha-galactosidase A gene causing the classical phenotype. Mol Genet Metab, 2002, 76(1): 23-30.
15.	Germain DP. Fabry disease. Orphanet J Rare Dis, 2010, 5(1): 30.
16.	Germain DP, Brand E, Burlina A, et al. Phenotypic characteristics of the p.Asn215Ser (p. N215S) GLA mutation in male and female patients with Fabry disease: a multicenter Fabry Registry study. Mol Genet Genomic Med, 2018, 6(4): 492-503.
17.	Pan X, Ouyang Y, Wang Z, et al. Genotype: a crucial but not unique factor affecting the clinical phenotypes in Fabry disease. PLoS One, 2016, 11(8): e0161330.
18.	Pieroni M, Moon JC, Arbustini E, et al. Cardiac involvement in Fabry disease: JACC review topic of the week. J Am Coll Cardiol, 2021, 77(7): 922-936.
19.	Weidemann F, Breunig F, Beer M, et al. The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease. Eur Heart J, 2005, 26(12): 1221-1227.
20.	Namdar M. Electrocardiographic changes and arrhythmia in Fabry disease. Front Cardiovasc Med, 2016, 3: 7.
21.	Parisi V, Baldassarre R, Ferrara V, et al. Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking. Front Cardiovasc Med, 2023, 10: 1184361.
22.	Allam C, Saouma M. Fabry disease and hypertrophic cardiomyopathy: similar albeit different. Eur Heart J, 2022, 43(Suppl_2): 1782.
23.	Mundigler G, Gaggl M, Heinze G, et al. The endocardial binary appearance (‘binary sign’) is an unreliable marker for echocardiographic detection of Fabry disease in patients with left ventricular hypertrophy. Eur J Echocardiogr, 2011, 12(10): 744-749.
24.	Graziani F, Lillo R, Panaioli E, et al. Prognostic significance of right ventricular hypertrophy and systolic function in Anderson-Fabry disease. ESC Heart Fail, 2020, 7(4): 1605-1614.
25.	Iorio A, Lucà F, Pozzi A, et al. Anderson-Fabry disease: red flags for early diagnosis of cardiac involvement. Diagnostics (Basel), 2024, 14(2): 208.
26.	Militaru S, Jurcu? R, Adam R, et al. Echocardiographic features of Fabry cardiomyopathy-Comparison with hypertrophy-matched sarcomeric hypertrophic cardiomyopathy. Echocardiography, 2019, 36(11): 2041-2049.
27.	Weidemann F, Beer M, Kralewski M, et al. Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: results from the SOPHIA study. Mol Genet Metab, 2019, 126(2): 169-182.
28.	Nordin S, Kozor R, Medina-Menacho K, et al. Proposed stages of myocardial phenotype development in Fabry disease. JACC Cardiovasc Imaging, 2019, 12(8 Pt 2): 1673-1683.
29.	中華醫學會心血管病學分會, 中華心血管病雜志編輯委員會. 成人法布雷病心肌病診斷與治療中國專家共識. 中華心血管病雜志, 2024, 52(2): 128-136.
30.	Spada M, Baron R, Elliott PM, et al. The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease - A systematic literature review by a European panel of experts. Mol Genet Metab, 2019, 126(3): 212-223.
31.	Lenders M, Menke ER, Brand E. Progress and challenges in the treatment of Fabry disease. BioDrugs, 2025, 39(4): 517-535.
32.	Holida M, Linhart A, Pisani A, et al. A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies. J Inherit Metab Dis, 2025, 48(1): e12795.
33.	Hughes D, Linhart A, Gurevich A, et al. Prompt agalsidase alfa therapy initiation is associated with improved renal and cardiovascular outcomes in a Fabry outcome survey analysis. Drug Des Devel Ther, 2021, 15: 3561-3572.
34.	Lenders M, Brand E. Effects of enzyme replacement therapy and antidrug antibodies in patients with Fabry disease. J Am Soc Nephrol, 2018, 29(9): 2265-2278.
35.	Linhart A, Dostálová G, Nicholls K, et al. Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study. Orphanet J Rare Dis, 2023, 18(1): 332.
36.	McCafferty EH, Scott LJ. Migalastat: a review in Fabry disease. Drugs, 2019, 79(5): 543-554.
37.	Hughes DA, Nicholls K, Shankar SP, et al. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet, 2017, 54(4): 288-296.
38.	Germain DP, Hughes DA, Nicholls K, et al. Treatment of Fabry’s disease with the pharmacologic chaperone migalastat. N Engl J Med, 2016, 375(6): 545-555.
39.	Guérard N, Oder D, Nordbeck P, et al. Lucerastat, an iminosugar for substrate reduction therapy: tolerability, pharmacodynamics, and pharmacokinetics in patients with Fabry disease on enzyme replacement. Clin Pharmacol Ther, 2018, 103(4): 703-711.
40.	Deegan PB, Goker-Alpan O, Geberhiwot T, et al. Venglustat, an orally administered glucosylceramide synthase inhibitor: assessment over 3 years in adult males with classic Fabry disease in an open-label phase 2 study and its extension study. Mol Genet Metab, 2023, 138(2): 106963.
41.	Zhao Z, Anselmo AC, Mitragotri S. Viral vector-based gene therapies in the clinic. Bioeng Transl Med, 2021, 7(1): e10258.
42.	Ali N, Gillespie S, Laney D. Treatment of depression in adults with Fabry disease. JIMD Rep, 2018, 38: 13-21.

1. Patel MR, Cecchi F, Cizmarik M, et al. Cardiovascular events in patients with Fabry disease natural history data from the Fabry registry. J Am Coll Cardiol, 2011, 57(9): 1093-1099.
2. O’Mahony C, Elliott P. Anderson-Fabry disease and the heart. Prog Cardiovasc Dis, 2010, 52(4): 326-335.
3. Hwu WL, Chien YH, Lee NC, et al. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c. 936+919G>A (IVS4+919G>A). Hum Mutat, 2009, 30(10): 1397-1405.
4. Gragnaniello V, Burlina AP, Polo G, et al. Newborn screening for Fabry disease in Northeastern Italy: results of five years of experience. Biomolecules, 2021, 11(7): 951.
5. Lv YL, Wang WM, Pan XX, et al. A successful screening for Fabry disease in a Chinese dialysis patient population. Clin Genet, 2009, 76(2): 219-221.
6. Li J, Pu L, Xu Z, et al. Screening for Fabry disease in patients with hypertrophic cardiomyopathy using cardiac magnetic resonance imaging. Eur Radiol, 2025, 35(5): 2888-2898.
7. Reisin R, Perrin A, García-Pavía P. Time delays in the diagnosis and treatment of Fabry disease. Int J Clin Pract, 2017, 71(1): e12914.
8. Ortiz A, Germain DP, Desnick RJ, et al. Fabry disease revisited: management and treatment recommendations for adult patients. Mol Genet Metab, 2018, 123(4): 416-427.
9. 中國法布雷病專家協作組. 中國法布雷病診療專家共識(2021 年版). 中華內科雜志, 2021, 60(4): 321-330.
10. Giammanco A, Gagliardo CM, Scrimali C, et al. Clinical and biochemical characterization of Fabry disease associated GLA gene variants: data from a large cohort of 469 thousand genotyped subjects of the UK Biobank Database. J Inherit Metab Dis, 2025, 48(6): e70103.
11. Oliveira JP, Ferreira S. Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype-phenotype correlations. Appl Clin Genet, 2019, 12: 35-50.
12. Sakuraba H, Togawa T, Tsukimura T, et al. Plasma lyso-Gb3: a biomarker for monitoring Fabry patients during enzyme replacement therapy. Clin Exp Nephrol, 2018, 22(4): 843-849.
13. Sivley MD, Wallace EL, Warnock DG, et al. Conjunctival lymphangiectasia associated with classic Fabry disease. Br J Ophthalmol, 2018, 102(1): 54-58.
14. Shabbeer J, Yasuda M, Luca E, et al. Fabry disease: 45 novel mutations in the alpha-galactosidase A gene causing the classical phenotype. Mol Genet Metab, 2002, 76(1): 23-30.
15. Germain DP. Fabry disease. Orphanet J Rare Dis, 2010, 5(1): 30.
16. Germain DP, Brand E, Burlina A, et al. Phenotypic characteristics of the p.Asn215Ser (p. N215S) GLA mutation in male and female patients with Fabry disease: a multicenter Fabry Registry study. Mol Genet Genomic Med, 2018, 6(4): 492-503.
17. Pan X, Ouyang Y, Wang Z, et al. Genotype: a crucial but not unique factor affecting the clinical phenotypes in Fabry disease. PLoS One, 2016, 11(8): e0161330.
18. Pieroni M, Moon JC, Arbustini E, et al. Cardiac involvement in Fabry disease: JACC review topic of the week. J Am Coll Cardiol, 2021, 77(7): 922-936.
19. Weidemann F, Breunig F, Beer M, et al. The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease. Eur Heart J, 2005, 26(12): 1221-1227.
20. Namdar M. Electrocardiographic changes and arrhythmia in Fabry disease. Front Cardiovasc Med, 2016, 3: 7.
21. Parisi V, Baldassarre R, Ferrara V, et al. Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking. Front Cardiovasc Med, 2023, 10: 1184361.
22. Allam C, Saouma M. Fabry disease and hypertrophic cardiomyopathy: similar albeit different. Eur Heart J, 2022, 43(Suppl_2): 1782.
23. Mundigler G, Gaggl M, Heinze G, et al. The endocardial binary appearance (‘binary sign’) is an unreliable marker for echocardiographic detection of Fabry disease in patients with left ventricular hypertrophy. Eur J Echocardiogr, 2011, 12(10): 744-749.
24. Graziani F, Lillo R, Panaioli E, et al. Prognostic significance of right ventricular hypertrophy and systolic function in Anderson-Fabry disease. ESC Heart Fail, 2020, 7(4): 1605-1614.
25. Iorio A, Lucà F, Pozzi A, et al. Anderson-Fabry disease: red flags for early diagnosis of cardiac involvement. Diagnostics (Basel), 2024, 14(2): 208.
26. Militaru S, Jurcu? R, Adam R, et al. Echocardiographic features of Fabry cardiomyopathy-Comparison with hypertrophy-matched sarcomeric hypertrophic cardiomyopathy. Echocardiography, 2019, 36(11): 2041-2049.
27. Weidemann F, Beer M, Kralewski M, et al. Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: results from the SOPHIA study. Mol Genet Metab, 2019, 126(2): 169-182.
28. Nordin S, Kozor R, Medina-Menacho K, et al. Proposed stages of myocardial phenotype development in Fabry disease. JACC Cardiovasc Imaging, 2019, 12(8 Pt 2): 1673-1683.
29. 中華醫學會心血管病學分會, 中華心血管病雜志編輯委員會. 成人法布雷病心肌病診斷與治療中國專家共識. 中華心血管病雜志, 2024, 52(2): 128-136.
30. Spada M, Baron R, Elliott PM, et al. The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease - A systematic literature review by a European panel of experts. Mol Genet Metab, 2019, 126(3): 212-223.
31. Lenders M, Menke ER, Brand E. Progress and challenges in the treatment of Fabry disease. BioDrugs, 2025, 39(4): 517-535.
32. Holida M, Linhart A, Pisani A, et al. A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies. J Inherit Metab Dis, 2025, 48(1): e12795.
33. Hughes D, Linhart A, Gurevich A, et al. Prompt agalsidase alfa therapy initiation is associated with improved renal and cardiovascular outcomes in a Fabry outcome survey analysis. Drug Des Devel Ther, 2021, 15: 3561-3572.
34. Lenders M, Brand E. Effects of enzyme replacement therapy and antidrug antibodies in patients with Fabry disease. J Am Soc Nephrol, 2018, 29(9): 2265-2278.
35. Linhart A, Dostálová G, Nicholls K, et al. Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study. Orphanet J Rare Dis, 2023, 18(1): 332.
36. McCafferty EH, Scott LJ. Migalastat: a review in Fabry disease. Drugs, 2019, 79(5): 543-554.
37. Hughes DA, Nicholls K, Shankar SP, et al. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet, 2017, 54(4): 288-296.
38. Germain DP, Hughes DA, Nicholls K, et al. Treatment of Fabry’s disease with the pharmacologic chaperone migalastat. N Engl J Med, 2016, 375(6): 545-555.
39. Guérard N, Oder D, Nordbeck P, et al. Lucerastat, an iminosugar for substrate reduction therapy: tolerability, pharmacodynamics, and pharmacokinetics in patients with Fabry disease on enzyme replacement. Clin Pharmacol Ther, 2018, 103(4): 703-711.
40. Deegan PB, Goker-Alpan O, Geberhiwot T, et al. Venglustat, an orally administered glucosylceramide synthase inhibitor: assessment over 3 years in adult males with classic Fabry disease in an open-label phase 2 study and its extension study. Mol Genet Metab, 2023, 138(2): 106963.
41. Zhao Z, Anselmo AC, Mitragotri S. Viral vector-based gene therapies in the clinic. Bioeng Transl Med, 2021, 7(1): e10258.
42. Ali N, Gillespie S, Laney D. Treatment of depression in adults with Fabry disease. JIMD Rep, 2018, 38: 13-21.

West China Medical Journal

Life-cycle management of Fabry cardiomyopathy

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