Screening for Fabry Disease in patients with unexplained left ventricular hypertrophy.
Chandu SadasivanJosie T Y ChowBun ShengDavid K H ChanYiting FanPaul C L ChoiJeffrey K T WongMabel M B TongTsz-Ngai ChanErik FungKevin K H KamJoseph Y S ChanWai-Kin ChiD Ian PatersonManohara SenaratneNeil BrassGavin Y OuditAlex P W LeePublished in: PloS one (2020)
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.
Keyphrases
- left ventricular
- deep brain stimulation
- hypertrophic cardiomyopathy
- ejection fraction
- end stage renal disease
- heart failure
- newly diagnosed
- acute myocardial infarction
- aortic stenosis
- mitral valve
- prognostic factors
- gene expression
- cardiac resynchronization therapy
- left atrial
- pulmonary hypertension
- genome wide
- atrial fibrillation
- copy number
- label free
- diabetic rats
- patient reported outcomes
- transcatheter aortic valve replacement
- drug induced
- stress induced
- genome wide identification