Fabry disease and hypertrophic cardiomyopathy: similar albeit different

Abstract

Abstract Background Fabry disease (FD) is a lysosomal storage disease that affects one or multiple organ systems and can cause left ventricular hypertrophy (LVH). FD can mimic hypertrophic cardiomyopathy (HCM), and clinicians occasionally miss the diagnosis of FD for HCM. The factors associated with FD-HCM misdiagnosis remain unclear. Purpose We sought to determine the prevalence of FD among patients with LVH and uncover the factors associated with FD-HCM misdiagnosis. Methods We searched online databases for all studies that performed a screening for FD in patients with LVH with reporting of a prevalence. We constructed a list of patients with LVH diagnosed with FD and collected their clinical, echocardiographic, and electrocardiographic characteristics and GLA gene mutation. We classified LVH as symmetric or asymmetric and GLA gene mutations as missense or non-missense. We calculated the prevalence of FD among patients with LVH adjusted for the founder effect. We later divided all FD patients into two groups depending on whether they were misdiagnosed for HCM (Group 1) or not misdiagnosed (Group 2). We used the chi-square and Student's t-test, respectively, to compare the quantitative and qualitative variables of Group 1 and Group 2. Results Thirty-one studies (n=11434 patients) met the inclusion criteria. There were 148 patients with LVH diagnosed with FD, and after adjusting for the founder effect, the prevalence of patients with LVH diagnosed with FD (n=117) was 1%. The number of FD patients misdiagnosed (Group 1) and not misdiagnosed (Group 2) for HCM was respectively 109 (73.6%) and 39 (26.4%). Patients in Group 1 were more likely to have an asymmetrical LVH, χ2(1, N=148)=18.6, p<0.001, a missense mutation, χ2(1, N=112)=7.8, p=0.0053 after adjusting for the founder effect, and a normal renal function, χ2(1, N=148)=16.2, p<0.001. The genetic results of five patients were missing. The maximal left ventricular wall thickness (LVWT) of Group 1 (M=19.84, SD=0.95) compared to Group 2 (M=17.58, SD=1.684) was significantly higher, t(109)=2.44, p=0.0165, and data were missing in 37 subjects. We did not find a significant difference in the following factors: age, nonclassic FD, angiokeratoma, acroparesthesia, stroke history, left ventricular outflow tract obstruction, history of syncope, atrioventricular block, history of tachyarrythmias, and history of pacemaker or defibrillator implantation. Conclusion FD is common among patients with LVH with a prevalence of 1%. Asymmetrical LVH and severe LVH are incorrectly thought to be uncommon in FD and tend to mislead clinicians in their diagnostic approach. FD patients with LVH and misdiagnosed HCM are more likely to have a missense mutation. FD patients with LVH and CKD are less likely to be misdiagnosed for HCM, and the most probable cause is that clinicians misdiagnosed some of these patients for CKD-related LVH. To conclude, we must increase awareness among clinicians on the red flags of FD. Funding Acknowledgement Type of funding sources: None.