Anderson–Fabry disease management: role of the cardiologist

Abstract

Anderson–Fabry disease (AFD) is a lysosomal storage disorder characterized by glycolipid accumulation in cardiac cells, associated with a peculiar form of hypertrophic cardiomyopathy (HCM). Up to 1% of patients with a diagnosis of HCM indeed have AFD. With the availability of targeted therapies for sarcomeric HCM and its genocopies, a timely differential diagnosis is essential. Specifically, the therapeutic landscape for AFD is rapidly evolving and offers increasingly effective, disease-modifying treatment options. However, diagnosing AFD may be difficult, particularly in the non-classic phenotype with prominent or isolated cardiac involvement and no systemic red flags. For many AFD patients, the clinical journey from initial clinical manifestations to diagnosis and appropriate treatment remains challenging, due to late recognition or utter neglect. Consequently, late initiation of treatment results in an exacerbation of cardiac involvement, representing the main cause of morbidity and mortality, irrespective of gender. Optimal management of AFD patients requires a dedicated multidisciplinary team, in which the cardiologist plays a decisive role, ranging from the differential diagnosis to the prevention of complications and the evaluation of timing for disease-specific therapies. The present review aims to redefine the role of cardiologists across the main decision nodes in contemporary AFD clinical care and drug discovery.

Genome-wide expression analysis in a Fabry disease human podocyte cell line

“…The diverse range of functions and interactions introduces a layer of biological complexity to these organelles [ 5 ]. A continuum of clinical severity is observed in FD, with the molecular abnormality and the sex of the patient being essential determinants [ 7 ]. The severity range spans from a severe classical phenotype to moderate nonclassical phenotype [ 8 ].…”

“…Symptoms encompass neuropathic pain, cornea verticillata, angiokeratoma, gastrointestinal involvement, sweating anomalies, hearing loss, hypertrophic cardiomyopathy, cardiac rhythm disorders, progressive renal failure, and stroke, with an onset in infancy [ 9 , 10 ]. The nonclassical phenotype is milder with a later onset, a more variable course of the disease, and can be limited to one or a small number of organs [ 7 ]. Despite the X-linked inheritance pattern, women often have signs and symptoms of FD related to random and/or skewed X inactivation, but are usually less severely affected compared to men [ 11 ].…”