AB018. Revisited later-onset cardiac type Fabry disease—cardiac damages progressed in silence—experiences from an extremely high prevalent area, Taiwan

Abstract: All of the current newborn screening studies of Fabry disease revealed that the incidences of later-onset Fabry disease in their studied populations were much higher than the previous expectancy. It reveals that later-onset Fabry disease could be an important hidden health issue in some populations or even a lot of populations. However, the natural course of later-onset Fabry disease is still largely unknown. A total of 792,247 newborns have been screened for Fabry disease by our team in Taiwan. Through this screening and pedigree study, more than 900 individuals were found to have a later-onset type mutation, IVS4+919G > A. The left ventricular hypertrophy (LVH) onset rate was analyzed through our patient database and gadolinium-enhanced cardiac magnetic resonance imaging (GE-CMRI) was performed in 73 IVS4 adults. LVH onset rate were 77% in male and 35% in female adults who were older than 40 years old. GE-CMRI revealed that 43% of males and 14.3% of females hadn’t LVH but had already developed significant myocardial delayed enhancement (MDE). Ten of patients who hadn’t LVH with MDE underwent endomyocardial biopsy and all revealed typical Fabry myocardial pathological findings with significant globotriaosylceramide accumulation in their cardiomyocytes. Our findings indicate that the current common consensus when to start ERT for cardiac Fabry patients might be inappropriately focusing on the existence of hypertrophic cardiomyopathy and its related symptoms/signs. An earlier intervention before significant cardiac manifestations have occurred in these later-onset Fabry patients might be necessary for a better outcome of enzyme replacement therapy.

Keywords: Newborn screening; Fabry disease