Screening for Fabry Disease in patients with unexplained left ventricular hypertrophy

Abstract

Fabry Disease (FD) is a systemic disorder that can result in cardiovascular, renal, and neurovascular disease leading to reduced life expectancy. FD should be considered in the differential of all patients with unexplained left ventricular hypertrophy (LVH). We therefore performed a prospective screening study in Edmonton and Hong Kong using Dried Blood Spot (DBS) testing on patients with undiagnosed LVH. Participants found to have unexplained LVH on echocardiography were invited to participate and subsequently subjected to DBS testing. DBS testing was used to measure α-galactosidase (α-GAL) enzyme activity and for mutation analysis of the α-galactosidase (GLA) gene, both of which are required to make a diagnosis of FD. DBS testing was performed as a screening tool on patients (n = 266) in Edmonton and Hong Kong, allowing for detection of five patients with FD (2% prevalence of FD) and one patient with hydroxychloroquine-induced phenocopy. Left ventricular mass index (LVMI) by GLA genotype showed a higher LVMI in patients with IVS4 + 919G > A mutations compared to those without the mutation. Two patients were initiated on ERT and hydroxychloroquine was discontinued in the patient with a phenocopy of FD. Overall, we detected FD in 2% of our screening cohort using DBS testing as an effective and easy to administer screening tool in patients with unexplained LVH. Utilizing DBS testing to screen for FD in patients with otherwise undiagnosed LVH is clinically important due to the availability of effective therapies and the value of cascade screening in extended families.

High Prevalence of Late-Onset Fabry Cardiomyopathy in a Cohort of 499 Non-Selective Patients with Left Ventricular Hypertrophy: The Asian Fabry Cardiomyopathy High-Risk Screening Study (ASIAN-FAME)

“…The present study is the first to systematically investigate the prevalence of FD among a non-selective Han Chinese patient population with LVH. Most previous FD screening studies in the LVH populations were predominantly targeted at non-Asian patients with unexplained and/or severe LVH [ 3 , 4 , 10 , 11 , 12 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Studies adopting a more all-inclusive screening approach generally yielded a low detection rate of less than 1% [ 30 ].…”

Mono-symptomatic Fabry disease in a population with mild-to-moderate left ventricular hypertrophy

“…A small study identified two patients from a cohort of 79 males with unexplained LGE on CMR, translating to 2.5% [ 5 ]. Another recent study of 266 patients with LVH identified five patients (2%) all with the intronic IVS4 + 919G > A genotype, known to be associated with late onset FD [ 13 ]. These five individuals were all of Chinese origin, a population where the IVS4 + 919G > A variant has a particularly high frequency [ 14 ].…”

High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review

“…The most common variant detected in the screening was IVS4+919G>A in Hong Kong and Japan, with a total of 11 individuals carrying this variant [82,92,97]. This variant was frequently detected in NBS in Taiwan and patients with late-onset FD with cardiac manifestations [17].…”

“…We reviewed 23 high-risk screenings for FD in individuals with cardiac manifestations (Table 2), with 20 screenings performed for individuals with either LVH or HCM [40,[80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98]. The other three screenings were performed in individuals with a variety of cardiac symptoms, including coronary artery disorders, conduction disorders, cardiomyopathy, and valvular disease [99], those with conduction disorders requiring a pacemaker [100], and those with left ventricular noncompaction (LVNC) [101].…”