Fabry disease: Biomarkers for screening and diagnosis

Fabry disease is a rare X-linked lysosomal storage disorder caused by absent or low enzyme activity of α-galactosidase A (α-GalA). The deficiency of α-GalA enzyme activity results in accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids, particularly in vascular endothelium, renal podocytes and cardiomyocytes, which leads to cerebrovascular, renal and cardiac complications, respectively. The disease has two major subtypes—an early-onset subtype in which patients develop “classic” symptoms during their childhood or early adolescence, and a “later-onset” subtype where patients have little or none of the “classic” symptoms but present predominantly or exclusively cardiac and/or renal manifestations in their forties or afterward. Enzyme replacement therapy (ERT) is available for the long-term clinical management of patients with either subtype. Current guidelines indicate that early intervention with ERT will provide the maximal benefits, especially for early-onset male patients. For patients with later-onset GLA mutations, treatment should start once there is evidence of end-organ injury. Therefore, a correct diagnosis and an early detection of end-organ damage are crucial for the timely initiation of the treatment. This article discusses the application and limitation of several diagnostic, predictive and prognostic biomarkers that are currently used in the clinical setting. Some new biomarkers in development are also briefly discussed.