Fabry Disease, a Rare Disorder with Cardiac Manifestations. The Problem of Diagnosis and Treatment: a Literature Review

DOI: https://doi.org/10.30702/ujcvs/22.30(04)/RN047-7380
Keywords: α-galactosidase A, enzyme replacement therapy, left ventricular hypertrophy, heart failure, systolic anterior motion

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disease caused by a mutation in the gene encoding α-galactosidase A and leads to reduced activity or complete absence of this enzyme, which causes the accumulation of globotriaosylceramide (Gb3) and its deacylated form (lyso-Gb3) in cells of the whole body. FD can occur both with multisystem manifestations, including damage to the nervous system, kidneys, and skin, and can affect only the heart. Cardiac involvement is a major cause of poor quality of life and death in patients with FD and an underrecognized cause of heart failure with preserved ejection fraction and ventricular arrhythmias in men over 30 years of age and women over 40 years of age. Cardiac damage begins at an early age, progresses subclinically until the appearance of significant symptoms, and usually manifests as leftventricular hypertrophy, mimicking hypertrophic cardiomyopathy.

After the introduction of enzyme replacement therapy, early recognition of FD and differential diagnosis with other causes of leftventricular hypertrophy have become crucial to limit the progression of the disease. Recent advances in the understanding of cardiac pathophysiology and imaging have improved diagnostic and therapeutic approaches to the cardiac manifestations of this pathology.

Modern achievements in the study of cardiac manifestations of FD have made it possible to significantly improve diagnostic and therapeutic approaches, in particular, in relation to the identification of pathogenetic mechanisms of organ damage and early disruption of their function. A better understanding of secondary pathogenic pathways, such as myocardial inflammation, may influence future therapeutic strategies and timely diagnosis of FD.

Delay in diagnosis and untimely initiation of treatment remain critical problems for many patients with FD, especially for patients with late-onset cardiovascular manifestations, in whom treatment effects may be more limited and ineffective.

Cooperation between specialists in genetic diseases and cardiologists remains important to identify patients before the appearance of cardiac symptoms in order to obtain maximum therapeutic effects.

References

  1. Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, et al. Fabry disease revisited: Management and treatment recommendations for adult patients. Mol Genet Metab. 2018;123(4):416-27. https://doi.org/10.1016/j.ymg-me.2018.02.014
  2. Ortiz A, Abiose A, Bichet DG, Cabrera G, Charrow J, Germain DP, et al. Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry. J Med Genet. 2016;53(7):495-502. https://doi.org/10.1136/jmedgenet-2015-103486
  3. Pieroni M, Moon JC, Arbustini E, Barriales-Villa R, Camporeale A, Vujkovac AC, et al. Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(7):922-36. https://doi.org/10.1016/j.jacc.2020.12.024
  4. Linhart A, Germain DP, Olivotto I, Akhtar MM, Anastasakis A, Hughes D, et al. An expert consensus document on the management of cardiovascular manifestations of Fabry disease. Eur J Heart Fail. 2020;22(7):1076-96. https://doi.org/10.1002/ejhf.1960
  5. Perry R, Shah R, Saiedi M, Patil S, Ganesan A, Linhart A, et al. Th e Role of Cardiac Imaging in the Diagnosis and Management of Anderson-Fabry Disease. JACC Cardiovasc Imaging. 2019;12(7 Pt 1):1230-42. https://doi.org/10.1016/j.jcmg.2018.11.039
  6. Doheny D, Srinivasan R, Pagant S, Chen B, Yasuda M, Desnick RJ. Fabry disease: prevalence of aff ected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995-2017. J Med Genet. 2018;55(4):261-8. https://doi.org/10.1136/jmedgenet-2017-105080
  7. Germain DP, Elliott PM, Falissard B, Fomin VV, Hilz MJ, Jovanovic A, et al. Th e effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts. Mol Genet Metab Rep. 2019;19:100454. https://doi.org/10.1016/j.ymgmr.2019.100454
  8. Van der Veen SJ, Hollak CEM, van Kuilenburg ABP, Langeveld M. Developments in the treatment of Fabry disease. J Inherit Metab Dis. 2020;43(5):908-21. https://doi.org/10.1002/jimd.12228
  9. Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W, et al. Improvement of Cardiac Function During Enzyme Replacement Therapy in Patients With Fabry Disease: A Prospective Strain Rate Imaging Study. Circulation. 2003;108(11):1299-301. https://doi.org/10.1161/01.CIR.0000091253.71282.04
  10. Hongo K, Ito K, Date T, Anan I, Inoue Y, Morimoto S, et al.The beneficial effects of long-term enzyme replacement therapy on cardiac involvement in Japanese Fabry patients. Mol Genet Metab. 2018;124(2):143-51 https://doi.org/10.1016/j.ymgme.2018.04.008
  11. Weidemann F, Niemann M, Breunig F, Herrmann S, Beer M, Störk S, et al. Long-Term Effects of Enzyme Replacement Therapy on Fabry Cardiomyopathy: Evidence for a Better Outcome With Early Treatment. Circulation. 2009;119(4):524-9. https://doi.org/10.1161/CIRCULATIONAHA.108.794529
  12. Weidemann F, Niemann M, Störk S, Breunig F, Beer M, Sommer C, et al. Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications. J Intern Med. 2013;274(4):331-41. https://doi.org/10.1111/joim.12077
  13. Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H, et al. High Incidence of Later-Onset Fabry Disease Revealed by Newborn Screening. Am J Hum Genet. 2006;79(1):31-40. https://doi.org/10.1086/504601
  14. Garg U, Dasouki M. Expanded newborn screening of inherited metabolic disorders by tandem mass spectrometry: Clinical and laboratory aspects. Clin Biochem. 2006;39(4):315-32. https://doi.org/10.1016/j.clinbiochem.2005.12.009
  15. Sorriento D, Iaccarino G. The Cardiovascular Phenotype in Fabry Disease: New Findings in the Research Field. Int J Mol Sci. 2021;22(3):1331. https://doi.org/10.3390/ijms22031331
  16. Namdar M. Electrocardiographic changes and arrhythmia in Fabry disease. Front Cardiovasc Med. 2016;3:7. https://doi.org/10.3389/fcvm.2016.00007
  17. Echevarria L, Benistan K, Toussaint A, Dubourg O, Hagege AA, Eladari D, et al. X-chromosome inactivation in female patients with Fabry disease. Clin Genet. 2016;89(1):44-54. https://doi.org/10.1111/cge.12613
  18. Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, et al. Fabry disease: Guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006;8(9):539-48. https://doi.org/10.1097/01.gim.0000237866.70357.c6
  19. Michaud M, Mauhin W, Belmatoug N, Bedreddine N, Garnotel R, Catros F, et al. Maladie de Fabry : quand y penser? [Fabry disease: A review]. Rev Med Interne. 2021;42(2):110-19. French. https://doi.org/10.1016/j.revmed.2020.08.019
  20. Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, et al. Fabry Registry. Females with Fabry disease frequently have major organ involvement: Lessons from the Fabry Registry. Mol Genet Metab. 2008;93(2):112-28. https://doi.org/10.1016/j.ymgme.2007.09.013
  21. Linhart A, Kampmann C, Zamorano JL, Sunder-Plassmann G, Beck M, Mehta A, et al.; European FOS Investigators. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J. 2007;28(10):1228-35. https://doi.org/10.1093/eurheartj/ehm153
  22. Elliott P, McKenna WJ. Hypertrophic cardiomyopathy. Lancet. 2004;363(9424):1881-91. https://doi.org/10.1016/S0140-6736(04)16358-7
  23. Chimenti C, Pieroni M, Morgante E, Antuzzi D, Russo A, Russo MA, et al. Prevalence of Fabry Disease in Female Patients With Late-Onset Hypertrophic Cardiomyopathy. Circulation. 2004;110(9):1047-53. https://doi.org/10.1161/01.CIR.0000139847.74101.03
  24. Lobo T, Morgan J, Bjorksten A, Nicholls K, Grigg L, Centra E, et al. Cardiovascular testing in Fabry disease: exercise capacity reduction, chronotropic incompetence and improved anaerobic threshold after enzyme replacement. Intern Med J. 2008;38(6):407-14. https://doi.org/10.1111/j.1445-5994.2008.01669.x
  25. Weidemann F, Niemann M, Sommer C, Beer M, Breunig F, Wanner C. Interdisciplinary approach towards female patients with Fabry disease. Eur J Clin Invest. 2012;42(4):455-62. https://doi.org/10.1111/j.1365-2362.2011.02614.x
  26. O’Mahony C, Elliott P, McKenna W. Sudden Cardiac Death in Hypertrophic Cardiomyopathy. Circ Arrhythm Electrophysiol. 2013;6(2):443-51. https://doi.org/10.1161/CIRCEP. 111.962043
  27. Kampmann C, Wiethoff CM, Whybra C, Baehner FA, Mengel E, Beck M. Cardiac manifestations of Anderson-Fabry disease in children and adolescents. Acta Paediatr. 2008;97(4):463-9. https://doi.org/10.1111/j.1651-2227.2008.00700.x
  28. Sachdev B, Takenaka T, Teraguchi H, Tei C, Lee P, McKenna WJ, et al. Prevalence of Anderson-Fabry Disease in Male Patients With Late Onset Hypertrophic Cardiomyopathy. Circulation. 2002;105(12):1407-11. https://doi.org/10.1161/01.cir.000001 2626. 81324.38
  29. Wu JC, Ho CY, Skali H, Abichandani R, Wilcox WR, Banikazemi M, et. al. Cardiovascular manifestations of Fabry disease: relationships between left ventricular hypertrophy, disease severity, and alpha-galactosidase A activity. Eur Heart J. 2010;31(9):1088-97. https://doi.org/10.1093/eurheartj/ehp588
  30. Palecek T, Dostalova G, Kuchynka P, Karetova D, Bultas J, Elleder M, et al. Right Ventricular Involvement in Fabry Disease. J Am Soc Echocardiogr. 2008;21(11):1265-8. https://doi.org/10.1016/j.echo.2008.09.002
  31. Serra W, Marziliano N. Role of cardiac imaging in Anderson-Fabry cardiomyopathy. Cardiovasc Ultrasound. 2019;17(1):1. https://doi.org/10.1186/s12947-019-0151-5
  32. Costanzo L, Buccheri S, Capranzano P, Di Pino L, Curatolo G, Rodolico M, et al. Early cardiovascular remodelling in Fabry disease. J Inherit Metab Dis. J Inherit Metab Dis. 2014;37(1):109-16. https://doi.org/10.1007/s10545-013-9607-1
  33. Tschöpe C, Dominguez F, Canaan-Kühl S, Blaschke D, Kühl U, Pieske B, et al. Endomyocardial biopsy in Anderson-Fabry disease: The key in uncertain cases. Int J Cardiol. 2015;190:284-6. https://doi.org/10.1016/j.ijcard.2015.04.130
  34. Yogasundaram H, Nikhanj A, Putko BN, Boutin M, Jain-Ghai S, Khan A, et al. Elevated Inflammatory Plasma Biomarkers in Patients With Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2018;7(21):e009098. https://doi.org/10.1161/JAHA.118.009098
  35. Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). 2014;35(39):2733-79. https://doi.org/10.1093/eurheartj/ehu284
  36. Kunkala MR, Aubry MC, Ommen SR, Gersh BJ, Schaff HV. Outcome of Septal Myectomy in Patients With Fabry›s Disease. Ann Thorac Surg. 2013;95(1):335-7. https://doi.org/10.1016/j.athoracsur.2012.05.087
  37. Ikeda K, Hirayama M, Hirota Y, Asa E, Seki J, Tanaka Y. Drug-induced phospholipidosis is caused by blockade of mannose 6-phosphate receptor-mediated targeting of lysosomal enzymes. Biochem Biophys Res Commun. 2008;377(1):268-74. https://doi.org/10.1016/j.bbrc.2008.09.121
  38. Fine NM, Wang Y, Khan A. Acute Decompensated Heart Failure After Initiation of Amiodarone in a Patient With Anderson-Fabry Disease. Can J Cardiol. 2019;35(1):104.e5-104.e7. https://doi.org/10.1016/j.cjca.2018.10.004
  39. Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, et al. Treatment of Fabry’s Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016;375(6):545-55. https://doi.org/10.1056/NEJMoa1510198
  40. Lenders M, Nordbeck P, Kurschat C, Karabul N, Kaufeld J, Hennermann JB, et al. Treatment of Fabry’s Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS). Clin Pharmacol Ther. 2020;108(2):326-37. https://doi.org/10.1002/cpt.1832
Published
2022-12-26
How to Cite
Rudenko, K. V., Nevmerzhytska, L. O., Unitska, O. M., Danchenko, P. A., & Leiko, N. S. (2022). Fabry Disease, a Rare Disorder with Cardiac Manifestations. The Problem of Diagnosis and Treatment: a Literature Review. Ukrainian Journal of Cardiovascular Surgery, 30(4), 73-80. https://doi.org/10.30702/ujcvs/22.30(04)/RN047-7380
Issue
Ukrainian Journal of Cardiovascular Surgery Vol 30 No 4 2022
Section
MYOCARDIAL PATHOLOGY AND HEART FAILURE