Prevalence and Clinical Characteristics of Fabry Disease in Chinese Patients With Hypertrophic Cardiomyopathy

Xiao, Yan; Sun, Yang; Tian, Tao; Wang, Tianjie; Zhao, Ranxu; Zhang, Ying; Wang, Linping; Liu, Yaxin; Lu, Chaoxia; Zhou, Xian‐Liang; Yang, Wei

doi:10.1016/j.amjms.2021.01.009

Cited by 8 publications

(2 citation statements)

References 40 publications

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“…When FD has hypertrophy as its main manifestation, it may be clinically grouped with hypertrophic cardiomyopathy prior to genetic testing. Wei-Xian Yang [ 16 ] et al reported that FD is not rare in hypertrophic cardiomyopathy patients in China, with an incidence of 0.93%. T1 mapping of cardiac MR can potentially detect early cardiac damage and differentiate left ventricular hypertrophy (LVH) due to FD from other diseases.…”

Section: Discussionmentioning

confidence: 99%

Case report and literature review: Fabry disease misdiagnosing as polymyalgia rheumatica

Yanfang,

Juanjuan,

Shengli

et al. 2023

Medicine

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Rationale: The clinical manifestations of Fabry disease affect the nerves, kidneys, heart, skin, gastrointestinal tract and eyes. Our aim is to familiarize people with the FD diagnostic process by reporting this case. Patient concerns: A 79-year-old-male patient presented with muscle pain and weakness in the extremities, also with an increasing erythrocyte sedimentation rate and C-reactive protein. Further examinations revealed that multiple organ involvement, such as rash, myocardial hypertrophy, peripheral neuropathy. Diagnoses: Cardiac MR demonstrated hypertrophic cardiomyopathy, myocardial fibrosis and low myocardial T1 value. The patient was eventually diagnosed with Fabry disease through proteomics and genetic testing. Interventions: The treatment is enzyme replacement therapy (ERT). But this patient could not afford ERT and was given only general symptomatic treatment, pregabalin, and a gradual reduction in glucocorticoid. Outcomes: The patient’s symptoms of joint pain and muscle weakness reduced significantly, and ESR and CRP had decreased to normal. Lessons: FD is a rare disease and difficult to diagnose, but rare does not mean invisible. FD may present with signs and symptoms of rheumatic diseases. Rheumatologists should be aware and concerned about this disease.

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Section: Discussionmentioning

confidence: 99%

Case report and literature review: Fabry disease misdiagnosing as polymyalgia rheumatica

Yanfang,

Juanjuan,

Shengli

et al. 2023

Medicine

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“…Modern technologies of massive parallel sequencing (NGS) are often used for the simultaneous analysis of the mutations of several genes that can cause diseases with similar phenotypes (for example, diagnosis of Pompe disease and other diseases with primary muscular lesions) [ 6 ]. However, currently, there is only one description of screening via NGS for the atypical form of FD in a small cohort of Chinese patients with HCM [ 57 ]. In the work of these colleagues, two patients with FD were revealed, which showed a percentage of FD diagnosis among the examined Chinese patients with HCM equal to 0.93%.…”

Section: Introductionmentioning

confidence: 99%

The prevalence of Fabry disease among 1009 unrelated patients with hypertrophic cardiomyopathy: a Russian nationwide screening program using NGS technology

Savostyanov

Pushkov

Жанин

et al. 2022

Orphanet J Rare Dis

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Background There is a vast number of screening studies described in the literature from the beginning of the twenty-first century to the present day. Many of these studies are related to the estimation of Fabry disease (FD) morbidity among patients from high-risk groups, including adult patients with hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH). These studies show diverse detection frequencies (0–12%) depending on the methodology. Our study is the only example of large-scale selective FD screening based on the implementation of next-generation sequencing technology (NGS) as a first-level test to estimate FD morbidity in the Russian population over 18 years of age burdened with HCM. Methods The study included 1009 patients (578 males and 431 females), with a median age of 50 years, who were diagnosed with HCM according to current clinical guidelines. In the first stage of screening, all patients underwent molecular genetic testing (NGS method) of target regions. These regions included the coding sequences of 17 genes and mutations that can lead to the development of HCM. Lysosomal globotriaosylsphingosine (lyso-Gb3) concentrations and α-galactosidase A (α-gal A) enzyme activity were measured in the second stage of screening to reveal pathogenic or likely pathogenic variants in the GLA gene. Results We revealed 8 (0.8%) patients (3 (37.5%) males and 5 (62.5%) females) with an average age of 59 ± 13.3 years who had pathogenic, likely pathogenic variants and variants of uncertain significance (VUS) in the GLA gene (NM_000169.2) as a result of selective screening of 1009 Russian patients with HCM. FD was confirmed via biochemical tests in a male with the pathogenic variant c.902G > A, p.R301Q as well as in two females with likely pathogenic variants c.897C > A, p.D299E and c.1287_1288dup, p.*430Fext*?. These tests showed reduced enzymatic activity and increased substrate concentration. However, a female with the pathogenic variant c.416A > G, p.N139S and with normal enzymatic activity only had increased substrate concentrations. The revealed nucleotide variants and high values of biochemical indicators (lyso-Gb3) in these 4 patients allowed us to estimate the FD diagnosis among 1009 Russian patients with HCM. Mild extracardiac manifestations were observed in these four patients; however, both biochemical values within the reference range in females with the c.971T > G, p.L324W (VUS) variant. α-gal A activity and lyso-Gb3 concentrations were also within the normal range in two males with hemizygous variants, c.546T > C, p.D182D and c.640-794_640-791del (we regarded them as VUS), and in one female with the c.427G > A, p.A143T variant (with conflicting interpretations of pathogenicity). Conclusion The prevalence rate of FD among 1,009 adult Russian patients with HCM was 0.4%. We recommend FD screening among adult patients of both sexes with HCM and an undefined genetic cause via NGS method with subsequent analysis of α-gal A activity and lyso-Gb3 concentration in patients with pathogenic, likely pathogenic variants, and VUS. This strategy identifies patients with an atypical form of FD that is characterized by high residual activity of α-gal A, low concentrations of lyso-Gb3, and minor extracardiac manifestations.

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Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study

Lin,

Zhang,

Liu

et al. 2024

ESC Heart Failure

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AimsLeft ventricular hypertrophy (LVH) is frequently detected via echocardiography in individuals with Fabry disease (FD), sometimes leading to confusion with hypertrophic cardiomyopathy (HCM) of other aetiologies. Considering this diagnosis challenge, FD should be included in the list of differential diagnosis for patients presenting with LVH. To address this concern, we conducted a prospective screening study in China, using dried blood spot (DBS) testing, to evaluate patients with unexplained LVH.MethodsOur study was designed as a nationwide, multicentre prospective investigation. A total of 1015 patients from 55 different centres who were diagnosed with LVH by echocardiography were screened in the study from September 2022 to December 2023. Demographic information, biochemistry data, echocardiography parameters and clinical observations were meticulously collected from all participants. The DBS method was used to assess α‐galactosidase A (α‐Gal A) activity in males and both α‐Gal A and globotriaosylsphingosine (lyso‐Gb3) levels in females.ResultsThe final screening population included 906 patients (589 males, 65%) with LVH, characterized by a mean maximal myocardial thickness of 14.8 ± 4.6 mm and an average age of 56.9 ± 17.2 years. In total, 43 patients (38 males, 5 females) exhibited low α‐Gal A activity measurement (<2.2 μmol/L), while 21 patients (10 males, 11 females) presented low α‐Gal A activity or elevated lyso‐Gb3 levels (>1.1 ng/mL). Among these patients, eight individuals (7 males and 1 female) were genetically confirmed to harbour pathogenic GLA mutations, resulting in a total prevalence of 0.88%. Compared with patients without FD, patients with FD tended to have proteinuria (75% vs. 21.2%, P = 0.001), family history of HCM (37.5% vs. 2.3%, P < 0.01) and neuropathic pain (37.5% vs. 4.4%, P < 0.01) but lower systolic blood pressure (118.5 ± 12.5 vs. 143.3 ± 29.3 mmHg, P = 0.017). Five mutations were previously recognized as associated with FD while the remaining two, p.Asp313Val (c.938A>T) and c.547+3A>G, were deemed potentially pathogenic. Subsequent familial validation post‐diagnosis identified an additional 14 confirmed cases.ConclusionsThis pioneering screening study for FD among Chinese patients with unexplained LVH using DBS measurement, revealed an FD detection rate of 0.88%. Our findings confirmed that the combined measurement of lyso‐Gb3 and α‐Gal A activity is beneficial for primary screening of FD in patients with LVH. Given the availability of efficacious therapies and the value of cascade screening in extended families, early detection of FD in LVH patients is clinically important.

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Prevalence and Clinical Characteristics of Fabry Disease in Chinese Patients With Hypertrophic Cardiomyopathy

Cited by 8 publications

References 40 publications

Case report and literature review: Fabry disease misdiagnosing as polymyalgia rheumatica

Case report and literature review: Fabry disease misdiagnosing as polymyalgia rheumatica

The prevalence of Fabry disease among 1009 unrelated patients with hypertrophic cardiomyopathy: a Russian nationwide screening program using NGS technology

Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study

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