Abstract
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.
Highlights
Fabry Disease OverviewGLA mutations leading to a residual enzymatic activity are associated to attenuated and late-onset phenotypes, which are characterized by the development of cardiac, renal and/or cerebrovascular manifestations in adulthood [2,3,4,5]
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It allows to differentiate Fabry disease (FD) from sarcomeric Hypertrophic cardiomyopathy (HCM), which usually results in late gadolinium enhancement (LGE) at the right ventricular (RV) junction points, and amyloidosis, which usually results in a global subendocardial pattern of LGE [51]
Summary
GLA mutations leading to a residual enzymatic activity are associated to attenuated and late-onset phenotypes, which are characterized by the development of cardiac, renal and/or cerebrovascular manifestations in adulthood [2,3,4,5]. In this X-linked disorder, heterozygote females are not merely carriers and their clinical spectrum widely ranges from asymptomatic to full-blown disease as severe as in affected males [6,7]
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