Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study
Abstract Aims Left 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...
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2024-12-01
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| Series: | ESC Heart Failure |
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| Online Access: | https://doi.org/10.1002/ehf2.15065 |
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| author | Zongwei Lin Xinyu Zhang Yan Liu Dongxia Miao Huanyi Zhang Tao Zhang Fenglei Zhang Peng Li Hongyan Dai Guihua Jiang Dongxia Zhang Lin Zhong Huixia Lu Xiaoping Ji |
| author_facet | Zongwei Lin Xinyu Zhang Yan Liu Dongxia Miao Huanyi Zhang Tao Zhang Fenglei Zhang Peng Li Hongyan Dai Guihua Jiang Dongxia Zhang Lin Zhong Huixia Lu Xiaoping Ji |
| author_sort | Zongwei Lin |
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| description | Abstract Aims Left 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. Methods Our 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. Results The 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. Conclusions This 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. |
| format | Article |
| id | doaj-art-ee1a6dec6d1c47039f896d06113619e1 |
| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
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| series | ESC Heart Failure |
| spelling | doaj-art-ee1a6dec6d1c47039f896d06113619e12024-12-11T01:57:00ZengWileyESC Heart Failure2055-58222024-12-011164381438910.1002/ehf2.15065Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective studyZongwei Lin0Xinyu Zhang1Yan Liu2Dongxia Miao3Huanyi Zhang4Tao Zhang5Fenglei Zhang6Peng Li7Hongyan Dai8Guihua Jiang9Dongxia Zhang10Lin Zhong11Huixia Lu12Xiaoping Ji13National Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology Qilu Hospital of Shandong University Jinan ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology Qilu Hospital of Shandong University Jinan ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology Qilu Hospital of Shandong University Jinan ChinaDepartment of Cardiology Dongying People's Hospital Dongying ChinaDepartment of Cardiology Tai'an Central Hospital Tai'an ChinaDepartment of Cardiology People's Hospital of Ningjin County Shandong Province Dezhou ChinaDepartment of Cardiology Dongying People's Hospital Dongying ChinaDepartment of Cardiology Xintai Hospital of Chinese Traditional Medicine Tai'an ChinaDepartment of Cardiology Qingdao Municipal Hospital Qingdao ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology Qilu Hospital of Shandong University Jinan ChinaDepartment of Cardiology Affiliated Yantai Yuhuangding Hospital of Qingdao University Yantai ChinaDepartment of Cardiology Affiliated Yantai Yuhuangding Hospital of Qingdao University Yantai ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology Qilu Hospital of Shandong University Jinan ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology Qilu Hospital of Shandong University Jinan ChinaAbstract Aims Left 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. Methods Our 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. Results The 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. Conclusions This 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.https://doi.org/10.1002/ehf2.15065Fabry diseaseleft ventricular hypertrophydried blood spotGLA mutationsenzyme replacement therapy |
| spellingShingle | Zongwei Lin Xinyu Zhang Yan Liu Dongxia Miao Huanyi Zhang Tao Zhang Fenglei Zhang Peng Li Hongyan Dai Guihua Jiang Dongxia Zhang Lin Zhong Huixia Lu Xiaoping Ji Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study ESC Heart Failure Fabry disease left ventricular hypertrophy dried blood spot GLA mutations enzyme replacement therapy |
| title | Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study |
| title_full | Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study |
| title_fullStr | Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study |
| title_full_unstemmed | Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study |
| title_short | Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study |
| title_sort | screening for fabry disease in patients with left ventricular hypertrophy in china a multicentre and prospective study |
| topic | Fabry disease left ventricular hypertrophy dried blood spot GLA mutations enzyme replacement therapy |
| url | https://doi.org/10.1002/ehf2.15065 |
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