Prevalence of Fabry disease in a predominantly hypertensive population with left ventricular hypertrophy.

Published on Sep 10, 2013in International Journal of Cardiology3.229
· DOI :10.1016/J.IJCARD.2012.06.069
Wim Terryn12
Estimated H-index: 12
Gert Deschoenmakere1
Estimated H-index: 1
+ 9 AuthorsRaymond Vanholder120
Estimated H-index: 120
Abstract Background Patients with Fabry disease (FD) develop progressive left ventricular hypertrophy (LVH). In screening studies in patients with LVH, the prevalence of FD ranges from 0 to 12%. This variability is attributable to different factors like diverging inclusion and exclusion criteria, the evaluation of selected populations and suboptimal screening methods. In this study, we aimed to determine the prevalence of FD in an unselected population of everyday clinical practice presenting LVH, defined as a maximal end-diastolic septal or posterior wall thickness ≥13mm, without exclusion of patients with arterial hypertension or valvular pathology, and using optimal screening methods. Methods In adult males, a two-tier approach was used; α-Galactosidase A (aGAL A) activity was measured using a dried bloodspot test (DBS) and diagnosis was confirmed by mutation analysis of the GLA gene. In females, mutation analysis was the primary screening tool. Results 362 men and 178 women were screened. Six patients were diagnosed with a genetic sequence alteration of the GLA gene. One man had a novel mutation, GLA p.Ala5Glu (c.44C>A), presenting as classical FD. Another man and three women had the previously described GLA p.Ala143Thr (c.427G>A) mutation, which generally presents as an attenuated phenotype. One woman had a novel sequence alteration c.639+6A>C, which appeared to be a polymorphism. All true Fabry patients had arterial hypertension (AHT), and one had hypertrophic obstructive cardiomyopathy (HOCM). Conclusions In a group of unselected patients with LVH, we found a prevalence of Fabry disease of 0.9%. AHT or type of hypertrophy should not be an exclusion criterion for screening for FD.
📖 Papers frequently viewed together
714 Citations
130 Citations
636 Citations
#1Thomas P. Mechtler (Medical University of Vienna)H-Index: 14
#2Susanne Stary (Medical University of Vienna)H-Index: 10
Last. David C. Kasper (Medical University of Vienna)H-Index: 22
view all 9 authors...
Summary Background The interest in neonatal screening for lysosomal storage disorders has increased substantially because of newly developed enzyme replacement therapies, the need for early diagnosis, and technical advances. We tested for Gaucher's disease, Pompe's disease, Fabry's disease, and Niemann-Pick disease types A and B in an anonymous prospective nationwide screening study that included genetic mutation analysis to assess the practicality and appropriateness of including these disorder...
206 CitationsSource
#1Perry M. Elliott (UCL: University College London)H-Index: 112
#2RJ Baker (UCL: University College London)H-Index: 8
Last. Derralynn Hughes (UCL: University College London)H-Index: 58
view all 7 authors...
Objectives The prevalence of Anderson–Fabry disease (AFD) in patients presenting with unexplained left ventricular hypertrophy (LVH) is controversial. The aim of this study was to determine the prevalence of AFD in a large, consecutive cohort of patients with hypertrophic cardiomyopathy (HCM) using rapid mutation screening. Design, Setting and Patients A European multicentre cross-sectional study involving 13 referral centres. Inclusion criteria for the study were: men aged at least 35 years and...
130 CitationsSource
#1Albert Hagège (Paris V: Paris Descartes University)H-Index: 62
#2Eric CaudronH-Index: 11
Last. Dominique P. GermainH-Index: 59
view all 12 authors...
Background Patients with Fabry disease (FD) show left ventricular hypertrophy (LVH) mimicking hypertrophic cardiomyopathy (HCM) of sarcomeric origin and might benefit, if detected early, from specific enzyme replacement therapy. The prevalence of FD in patients with LVH of 13 mm or greater, screened using the leucocyte alpha-galactosidase A (a-gal A) activity test, a technique that is difficult to apply routinely, ranged from 0% to 6%. Objective To screen systematically for FD in patients with a...
57 CitationsSource
#1Andreas GalH-Index: 76
#2Derralynn Hughes (Royal Free Hospital)H-Index: 58
Last. Bryan Winchester (ICH: UCL Institute of Child Health)H-Index: 29
view all 3 authors...
Competing interest: None declared. This recommendation was compiled by the authors on behalf of the 21 European Experts listed in the article.
56 CitationsSource
#1Ole HavndrupH-Index: 18
#2Michael Christiansen (SSI: Statens Serum Institut)H-Index: 72
Last. Henning BundgaardH-Index: 50
view all 11 authors...
Aims Fabry disease, an X-linked storage disorder caused by defective lysosomal enzyme alpha-galactosidase A activity, may resemble sarcomere-gene-associated hypertrophic cardiomyopathy (HCM). The ‘cardiac variant’ of Fabry disease which only affects the heart may be missed unless specifically tested for. Methods and results We evaluated 90 consecutively recruited HCM probands and their relatives. Probands without sarcomere-gene mutations were tested for alpha-galactosidase A gene (GLA) mutations...
62 CitationsSource
#1Justina C. Wu (Brigham and Women's Hospital)H-Index: 6
#2Carolyn Y. Ho (Brigham and Women's Hospital)H-Index: 50
Last. Scott D. Solomon (Brigham and Women's Hospital)H-Index: 149
view all 9 authors...
Aims Fabry disease is a rare X-linked deficiency of α-galactosidase A (αgal), which causes glycosphingolipid accumulation. This study analysed the cardiovascular manifestations of a cohort of Fabry patients, and sought to define relationships between disease severity, αgal activity, and cardiac abnormalities. Methods and results We prospectively analysed Fabry patients (139 subjects: 92 males and 47 females) undergoing screening for potential enzyme replacement therapy. Baseline echocardiograms,...
42 CitationsSource
#1Gabor E. Linthorst (UvA: University of Amsterdam)H-Index: 42
#2Machtelt G. BouwmanH-Index: 10
Last. Carla E. M. HollakH-Index: 59
view all 6 authors...
Introduction: Fabry disease (FD) may present with left ventricular hypertrophy, renal insufficiency or stroke. Several studies investigated FD prevalence in populations expressing these symptoms. We conducted a systematic review to calculate the overall prevalence of FD in these cohorts. Methods: We searched online databases for studies on screening for FD. We recorded study population selection, screening methods and outcome of screening. Results: We identified 20 studies, 10 of which included ...
117 CitationsSource
#1Manesh R. Patel (Duke University)H-Index: 104
#2Franco CecchiH-Index: 55
Last. Ademola K. Abiose (UI: University of Iowa)H-Index: 5
view all 12 authors...
Objectives These analyses were designed to determine the incidence of major cardiovascular (CV) events and the natural history of CV complications in patients with Fabry disease. Background Fabry disease, a genetic disorder caused by deficiency of alpha-galactosidase A activity, is associated with CV dysfunction. Methods Major CV events (myocardial infarction, heart failure, or cardiac-related death) were analyzed in 2,869 Fabry Registry patients during the natural history period (i.e., before e...
97 CitationsSource
#1Atul Mehta (UCL: University College London)H-Index: 76
#2Mathias Beck (University of Mainz)H-Index: 32
Last. Jtr ClarkeH-Index: 2
view all 10 authors...
Summary Background We analysed 5-year treatment with agalsidase alfa enzyme replacement therapy in patients with Fabry's disease who were enrolled in the Fabry Outcome Survey observational database (FOS). Methods Baseline and 5-year data were available for up to 181 adults (126 men) in FOS. Serial data for cardiac mass and function, renal function, pain, and quality of life were assessed. Safety and sensitivity analyses were done in patients with baseline and at least one relevant follow-up meas...
219 CitationsSource
#1Wuh-Liang Hwu (NTU: National Taiwan University)H-Index: 58
#2Yin-Hsiu Chien (NTU: National Taiwan University)H-Index: 40
Last. Li-Wen Hsu (NTU: National Taiwan University)H-Index: 5
view all 12 authors...
Fabry disease (α-galactosidase A (α-Gal A, GLA) deficiency) is a panethnic inborn error of glycosphingolipid metabolism. Since optimal therapeutic outcomes depend on early intervention, a pilot program was designed to assess newborn screening for this disease in 171,977 consecutive Taiwanese newborns by measuring their dry blood spot (DBS) α-Gal A activities and β-galactosidase/α-Gal A ratios. Of the 90,288 male screenees, 638 (0.7%) had DBS α-Gal A activity 10. A second DBS assay reduced these ...
247 CitationsSource
Cited By30
#1Takaaki SawadaH-Index: 2
#2Jun KidoH-Index: 9
Last. Kimitoshi NakamuraH-Index: 26
view all 4 authors...
Fabry disease (FD) is an X-linked inherited disorder caused by mutations in the GLA gene, which encodes the lysosomal enzyme α-galactosidase A (α-Gal A). FD detection in patients at an early stage is essential to achieve sufficient treatment effects, and high-risk screening may be effective. Here, we performed high-risk screening for FD in Japan and showed that peripheral neurological manifestations are important in young patients with FD. Moreover, we reviewed the literature on high-risk screen...
#1Yiting Fan (CUHK: The Chinese University of Hong Kong)H-Index: 7
#2Tsz-Ngai ChanH-Index: 1
Last. Alex Pui-Wai LeeH-Index: 23
view all 13 authors...
Left ventricular hypertrophy (LVH) caused by cardiac variant Fabry disease (FD) is typically late-onset and may mimic LVH caused by abnormal loading conditions. We aimed to determine the prevalence of FD in a non-selective patient population of everyday practice presenting with LVH, including those with hypertension and valve disease. We measured plasma alpha-galactosidase A activity using dried blood spot tests in 499 (age = 66 ± 13 years; 336 men) Hong Kong Chinese patients with LVH defined as...
1 CitationsSource
#1Federica Rossi (University of Milano-Bicocca)H-Index: 8
#2Einar Svarstad (University of Bergen)H-Index: 26
Last. Federico Pieruzzi (University of Milano-Bicocca)H-Index: 22
view all 8 authors...
INTRODUCTION: Published data on hypertension incidence and management in Anderson-Fabry disease are scant and the contribution of elevated blood pressure to organ damage is not well recognized. AIM Therefore, we have assessed blood pressure values and their possible correlations with clinical findings in a well described cohort of Fabry patients. METHODS Between January 2015 and May 2019, all adult Fabry patients (n = 24 females, n = 8 males) referred to our institute were prospectively enrolled...
1 CitationsSource
Last. Fellype Carvalho Barreto (UFPR: Federal University of Paraná)H-Index: 16
view all 5 authors...
Purpose of review:In this narrative review, we describe general aspects, histological alterations, treatment, and implications of Fabry disease (FD) nephropathy. This information should be used to ...
#1Maria Fuller (University of Adelaide)H-Index: 31
#2Rebecca Perry (Flinders University)H-Index: 14
Last. Joseph B. Selvanayagam (Flinders University)H-Index: 47
view all 5 authors...
Abstract Fabry disease (FD) results from a deficiency in the exoglycohydrolase, α-galactosidase A (AGA), an enzyme required for the sequential degradation of glycosphingolipids, which consequently accumulate in the lysosomes of affected cells. An X-linked inherited metabolic disorder, FD has a high incidence of a later onset phenotype that is under-diagnosed and under-recognised in adulthood despite the availability of specific treatment. As the first presenting feature in adults is often left v...
1 CitationsSource
Fabry disease (FD) is a multisystemic X-linked disorder characterized by the accumulation of lysosomal globotriaosylceramide (Gb3) secondary to decreased activity of α-galactosidase in cells. Generally, males are more severely affected due to the X-linked inheritance pattern of the disease. However, females are asymptomatic or have a less severe pattern of disease. Enzyme replacement therapy (ERT) is the cornerstone of the treatment of FD. At present, there are two forms of ERT that can be appli...
4 CitationsSource
#1Aleš Linhart (First Faculty of Medicine, Charles University in Prague)H-Index: 57
Last. Perry M. Elliott (UCL: University College London)H-Index: 112
view all 13 authors...
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A gene (GLA) that leads to reduced or undetectable α-galactosidase A (AGAL-A) enzyme activity and progressive accumulation of globotriaosylceramide (Gb3 ) and its deacylated form globotriaosylsphingosine (lysoGb3 ) in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is charac...
17 CitationsSource
Abstract Background Fabry disease (FD) is a treatable cause of hypertrophic cardiomyopathy (HCM). We aimed to determine the independent predictors of FD and to define a clinically useful strategy to discriminate FD among HCM. Methods Multicenter study including 780 patients with the ESC definition of HCM. FD screening was performed by enzymatic assay in males and genetic testing in females. Multivariate regression analysis identified independent predictors of FD in HCM. A discriminant function a...
1 CitationsSource
#1Hasan Ali BarmanH-Index: 7
#2Baris Ikitimur (Istanbul University)H-Index: 9
Last. Hakan Karpuz (Istanbul University)H-Index: 5
view all 8 authors...
Aims: Fabry disease is an X-linked lysosomal storage disorder due to a deficiency of the α-galactosidase A enzyme. Cardiac involvement is present in over 60% of adult cases of Fabry disease. Hypertrophic cardiomyopathy without left ventricular outflow tract obstruction is the most common phenotype. The aim of the study was to screen adult patients with hypertrophic cardiomyopathy without left ventricular outflow tract.
3 CitationsSource
BACKGROUND: Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.Methods and Results:Between 2014 and 2016, both lyso-Gb3 and α...
2 CitationsSource