Fabry Disease and the Heart: A Comprehensive Review

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.

Pulvinar Sign, Stroke and Their Relationship with Fabry Disease: A Systematic Review and Metanalysis

“…To our current knowledge, there are two clinical phenotypes of Fabry disease: classical and later-onset (non-classical) phenotypes. In the non-classical phenotype, renal, cardiac, and/or cerebrovascular manifestations are seen in adulthood [33]. Within the later-onset form, there is also a particular late-onset phenotype with a predominant cardiac variant, an intronic variant (IVS4 + 919G > C), common in Asian countries [23].…”

Cardiac Magnetic Resonance in Fabry Disease: Morphological, Functional, and Tissue Features

“…All the signs and symptoms in childhood and teenage years should raise the suspicion of FD and induce clinicians to perform an alpha-galactosidase enzymatic activity test on plasma or the blood pool, and confirm the diagnosis with a genetic test. Enzymatic replacement therapy (ERT) is an etiological therapy that blocks the progression of disease, often with a regression of LV hypertrophy and improvement of the prognosis of the patients [ 5 ].…”

Clinical application of CMR in cardiomyopathies: evolving concepts and techniques

“…CMR techniques hold strong potential in AFD not only for guiding the appropriate timing for ERT introduction and prognostic classification, but also for monitoring response to therapy. For instance, several studies reported more effective results of ERT in terms of LV mass regression when little or no LGE was present at baseline evaluation [ 114 ] thus suggesting that specific treatment should be initiated earlier, as soon as the first structural or functional cardiac abnormalities become detectable and before development of myocardial fibrosis. Supplementary, material case 3 .…”