Cardiac

Cardiac symptoms are common in both males and females.¹ Cardiovascular disease is one of the most frequent causes of death in patients with Fabry disease.²

These defects cause dyspnoea, angina, palpitations and syncope.¹ Cardiac abnormalities may be observed in children; the earliest manifestation of abnormal cardiac rhythm is bradycardia; in male children (as young as 12 years), a reduction in heart rate variability has also been observed.^4,5 A recent study reported that cardiac arrhythmias were observed in males (but not females) of less than 18 years of age and recommended the routine performance of cardiac evaluation in teenage (and older) patients with Fabry disease.^5,6 Cardiac abnormalities in Fabry disease are associated with the accumulation of Gb₃ and other glycosphingolipids in the tissues, particularly in the endothelium and media of small blood vessels, the cardiac muscle and conducting fibres.⁷ Gb₃ storage induces progressive lysosomal and cellular malfunctioning that subsequently activates common signalling pathways, leading to hypertrophy, apoptosis, necrosis and cardiac fibrosis. The degree of fibrosis in Fabry disease varies depending on the stage of disease.¹ Left ventricular hypertrophy (LVH) is the predominant finding from echocardiograms and magnetic resonance imaging;^1,8 LVH is progressive and typically occurs earlier in males than in females.^1,8 Cardiovascular abnormalities make a substantial contribution to disease-related morbidity and mortality in males and may be the major cause of premature death.⁹