Journal of Rare Cardiovascular Diseases

Fabry disease is one of the lysosomal storage disorders, that results from progressive multiorgan accumulation of glycoproteins. It is caused by mutations of the GLA gene, which encodes alpha-galactosidase A. The  incidence of Fabry disease is estimated at the level of 1:55 000 male births, however the true prevalence, including atypical, sub-clinical or late-variant phenotypes may be higher. Typically, early manifestations of the disease, neuropathy and angiokeratomas, are evident by youth. Cardiac involvement results in left ventricle hypertrophy, although lysosomal deposits may lead to conduction disorders, coronary artery disease, aortic and mitral valve insuffi ciency. This review presents detailed description of Fabry disease pathophysiology, genetics and epidemiology. It provides the latest data on screening, diagnostics and management. JRCD 2012; 1: 3–6

 

Storage disease; Myocardial hypertrophy

Linhart A, Elliott PM. The heart in Anderson – Fabry disease and other lysosomal storage disorders. Heart 2007; 93: 528–535.

Zarate YA, Hopkin RJ. Fabry’s disease. Lancet 2008; 372: 1427–1435.

O’Mahony C, Elliott P. Anderson-Fabry disease and the heart. Prog Cardiovasc Dis. 2010; 52: 326–335.

Nakao S, Takenaka T, Maeda M, et al. An atypical variant of Fabry’s disease in men with left ventricular hypertrophy. New Eng J Med 1995; 333: 288–293.

Spada M, Pagliardini S, Yasuda M, et al. High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 2006; 79: 31–40.

Schiffmann R, Warnock DG, Banikazemi M, et al. Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transplant. 2009; 24: 2102–2111.

Vedder AC, Linthorst GE, van Breemen MJ, et al. The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels. J Inherit Metab Dis 2007; 30: 68–78.

Elleder M, Bradova V, Smid F, et al. Cardiocyte storage and hypertrophy as a sole manifestation of Fabry’s disease. Report on a case simulating hyper-trophic non-obstructive cardiomyopathy. Virchows Arch A Pathol Anat Histopathol 1990; 417: 449–455.

Elleder M. Sequelae of storage in Fabry disease—pathology and comparison with other lysosomal storage diseases. Acta Paediatr Suppl 2003;92:46–53.

Sachdev B, Takenaka T, Teraguchi H, et al. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation 2002; 105: 1407–1411.

Monserrat L, Gimeno-Blanes JR, Marin F, et al. Prevalence of Fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2007; 50: 2399–2403.

Chimenti C, Pieroni M, Morgante E, et al. Prevalence of Fabry disease in female patients with late -onset hypertrophic cardiomyopathy. Circulation 2004; 110: 1047–1053.

Calcagnino M, O’Mahony C, Coats C, et al. Exercise -induced left ventricular outflow tract obstruction in symptomatic patients with anderson-fabry disease. J Am Coll Cardiol. 2011; 58: 88–89.

Linhart A, Lubanda JC, Palecek T, et al. Cardiac manifestations in Fabry disease. J Inherit Metab Dis. 2001; 24 (Suppl 2): 75–83.

Dimitrow PP, Cheng TO. Standing position alone or in combination with exercise as a stress test to provoke left ventricular outflow tract gradient in hypertrophic ardiomyopathy and other conditions. Int J Cardiol. 2010; 143: 219–222.

Dimitrow PP, Bober M, Michałowska J, et al. Left ventricular outflow tract gradient provoked by upright position or exercise in treated patients with hypertrophic cardiomyopathy without obstruction at rest. Echocardiography. 2009; 26: 513–520.

Pinderski LJ, Strotmann J: Congestive heart failure in Fabry cardiomyopathy: Natural history experience in an international cohort of 1,448 patients. J Heart Lung Transplant 2006; 25: 70.

Pieroni M, Chimenti C, Ricci R, et al. Early detection of Fabry cardiomyopathy by tissue Doppler imaging. Circulation 2003; 107: 1978–1984.

Pieroni M, Chimenti C, Russo A, et al. Tissue Doppler imaging in Fabry disease. Curr Opin Cardiol 2004; 19: 452–457.

Moon JC, Sheppard M, Reed E, et al. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease. J Cardiovasc Magn Reson 2006; 8: 479–482.

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: 1221–1227.

Linhart A, Kampmann C, Zamorano JL, et al. Cardiac manifestations of Anderson – Fabry disease: results from the international Fabry outcome survey. Eur Heart J 2007; 28: 1228–1235.

Kovarnik T, Mintz GS, Karetova D, et al. Intravascular ultrasound assessment of coronary artery involvement in Fabry disease. J Inherit Metab Dis 2008; 31: 753–760.

Elliott PM, Kindler H, Shah JS, et al. Coronary microvascular dysfunction in male patients with Anderson-Fabry disease and the effect of treatment with alpha galactosidase A. Heart 2006; 92: 357–360.

Dimitrow PP, Krzanowski M, Undas A. Reduced coronary flow reserve in Anderson – Fabry disease measured by transthoracic Doppler echocardiography. Cardiovasc Ultrasound. 2005; 3: 11.

Senechal M, Germain DP. Fabry disease: a functional and anatomical study of cardiac manifestations in 20 hemizygous male patients. Clin Genet 2003; 63: 46–52.

Pochis WT, Litzow JT, King BG, et al. Electrophysiologic findings in Fabry’s disease with a short PR interval. Am J Cardiol 1994; 74: 203–204.

Jastrzebski M, Bacior B, Dimitrow PP, Kawecka – Jaszcz K. Electrophysiological study in a patient with Fabry disease and a short PQ interval. Europace. 2006; 8: 1045–1047.

Lobo T, Morgan J, Bjorksten A, et al. Cardiovascular testing in Fabry disease: exercise capacity reduction, chronotropic incompetence and improved an-aerobic threshold after enzyme replacement. Intern Med J 2008; 38: 407–414.

Shah JS, Hughes DA, Sachdev B, et al. Prevalence and clinical significance of cardiac arrhythmia in Anderson-Fabry disease. Am J Cardiol 2005; 96: 842–846.

Eckart RE, Kinney KG, Belnap CM, et al. Ventricular fibrillation refractory to automatic internal cardiac defibrillator in Fabry’s disease. Review of cardiovascular manifestations. Cardiology 2000; 94: 208–212.

Weidemann F, Strotmann JM, Niemann M, et al. Heart valve involvement in Fabry cardiomyopathy. Ultrasound Med Biol. 2009; 35: 730–735.

Linhart A, Palecek T, Bultas J, et al. New insights in cardiac structural changes in patients with Fabry’s disease. Am Heart J. 2000; 139: 1101–1108.

Spinelli L, Pisani A, Sabbatini M, et al . Enzyme replacement therapy with agalsidase beta improves cardiac involvement in Fabry’s disease. Clin Genet 2004; 66: 158–165.

Beer M, Weidemann F, Breunig F, et al. Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry’s cardiomyopathy. Am J Cardiol 2006; 97: 1515–1518.

Hughes DA, Elliott PM, Shah J, et al. Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa. Heart 2008; 94: 153–158.

Kovacevic – Preradovic T, Zuber M, Jost CH, et al. Anderson-Fabry disease: long-term echocardiographic follow-up under enzyme replacement therapy. Eur J Echocardiogr 2008; 9: 729–735.

Weidemann F, Niemann M, Breunig F, et al. Long-term effects of enzyme replacement therapy on Fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation 2009; 119: 524–529.

Waldek S. PR interval and the response to enzyme – replacement therapy for Fabry’s disease. N Engl J Med 2003; 348: 1186–1187.

Kalliokoski RJ, Kantola I, Kalliokoski KK, et al. The effect of 12 – month enzyme replacement therapy on myocardial perfusionin patients with Fabry disease. J Inherit Metab Dis 2006; 29: 112