Fabry disease and the heart

Fabry disease is induced by a mutation in the alpha-galactosidase A gene, causing a deficiency of the enzyme alpha-galactosidase A. (1) The enzyme defect leads to progressive intracellular accumulation of globotriaosylceramide in lysosomes of various tissues and organs, including heart, kidney and nerve system. Cardiac involvement is common and is presenting as concentric left ventricular hypertrophy. Myocardial replacement fibrosis is a typical feature of more advanced stages of Fabry cardiomyopathy, first limited to the mid-myocardial layers of the basal postero-lateral wall, then spreading to transmural fibrosis. Since 2001, enzyme replacement therapy is available. If therapy is started early, before myocardial fibrosis has developed, a long-term improvement of myocardial morphology, function and exercise capacity can be achieved. In end-stage cardiomyopathy enzyme replacement therapy might prevent further progression of the disease. This review provides an overview of Fabry disease, with a focus on cardiac involvement with its characteristic features, clinical presentation and possible treatment.