Cardiac Dysfunction

Cardiac involvement in Fabry disease varies considerably, but like most aspects of the disease, it increases in severity with age. Structural changes may not be associated with significant dysfunction, but serve as markers of disease progression.1

Cardiac manifestations

Common cardiac-related signs and symptoms include:1-2

  • Left ventricular hypertrophy
  • Valvular disease (especially mitral valve prolapse and/or regurgitation)
  • Premature coronary artery disease
  • Angina
  • Myocardial infarction
  • Conduction abnormalities
  • Arrhythmias
  • Congestive heart failure

ECG and echocardiographic findings

Characteristic electrocardiographic findings include AV conduction abnormalities (short P-R intervals or AV block), signs of left ventricular hypertrophy, and repolarization abnormalities (ST-T wave changes). Supraventricular arrhythmias may also be noted.3

Echocardiographic findings may include aortic root dilatation, enlarged ventricular mass, and valvular disease (especially of the mitral valve).

Left ventricular hypertrophy

Progressive GL-3 accumulation in myocardial cells may lead to significant enlargement of the heart, particularly the left ventricle.2-3 The main determinants of left ventricular mass appear to be age and α-galactosidase A (α-GAL) activity.4

50-year-old Fabry disease patient

Image shoes gross appearance of the heart (cut surface) from a 50-year-old Fabry disease patient with arrows denoting the markedly thick myocardium.

Gross appearance of the heart (cut surface) from a 50-year-old Fabry disease patient. Note markedly thickened myocardium. Used with permission from R.J. Desnick, MD, Phd.

Cardiac variant Fabry disease

Atypical variants are subtypes of Fabry disease patients who have residual levels of α-galactosidase A (α-GAL) and manifest few or none of the classical Fabry disease symptoms. Often in these patients, the disease predominantly affects one organ system. Cardiac variants are the most widely recognized and studied of these subtypes. In cardiac variants, disease manifestations typically present later in life and are limited to the heart. The vascular endothelium is generally not affected.5

 More information for cardiologists » 


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

2. Desnick RJ, YA Ioannou, CM Eng. α-galactosidase A deficiency: Fabry disease. In: The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill, 2001: 3733-3774.

3. Linhart A, JC Lubanda, T Palecek, et al. Cardiac manifestations in Fabry disease. J Inherit Metab Dis. 2001;24 Suppl 2:75-83; discussion 65.

4. Goldman ME, R Cantor, MF Schwartz, M Baker, RJ Desnick. Echocardiographic abnormalities and disease severity in Fabry's disease. J Am Coll Cardiol. 1986;7:1157-1161.

5.Carubbi F, Bonilauri L. Fabry disease: raising awareness of the disease among physicians. Intern Emerg Med 2012;7 Suppl 3:227-31.