High Prevalence of Late-Onset Fabry Cardiomyopathy in a Cohort of 499 Non-Selective Patients with Left Ventricular Hypertrophy: The Asian Fabry Cardiomyopathy High-Risk Screening Study (ASIAN-FAME)

Fan, Yiting; Chan, Tsz-Ngai; Chow, J.C.H.; Kam, Kevin Ka‐Ho; Kin, Wai; Chan, Joseph Yat‐Sun; Fung, Erik; Tong, Man; Wong, Jeffery K T; Choi, Pui–Wah; Chan, David K H; Sheng, Bun; Lee, Alex

doi:10.3390/jcm10102160

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…FD is a hereditary disorder linked to the X chromosome, meaning that men have a severe form of the disease and transmit it to all of their daughters, but not to their sons. Fabry disease can manifest as an earlier onset form that effects multiple organ systems or a later onset form that usually dominated by single organ system, which is often the heart [5] . The case presented here appears to fall into the latter category.…”

Section: Discussionmentioning

confidence: 75%

Fabry disease with acute myocardial infarction, left ventricular thrombosis, and pericardial effusion

Zhou

Wang

et al. 2022

Medicine

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Rationale: Fabry disease (FD) is a rare, X-linked lysosomal deposition disease characterized by multi-system symptoms. The accumulation of globotriaosylceramide in various organs, such as the kidneys and heart, as well as the nervous system, has been speculated to be the mechanism involved in tissue damage, including vascular impairment with thrombotic events.Patient concerns: Here, we describe a 72-year-old male patient diagnosed with FD, who first presented with acute myocardial infarction, left ventricular thrombosis, and pericardial effusion, accompanied by cardiac hypertrophy.Diagnoses: A physical examination showed that he was hemodynamically stable and an electrocardiogram showed ventricular tachycardia (Fig. 1A). The single obvious abnormality was an ST segment depression with a preterminal negative T wave in leads I and aVL (Fig. 1B). Coronary angiography revealed regular findings (Fig. 2). Echocardiogram conducted at our hospital revealed hypertrophy, ejection fraction 40%, pericardial effusion (Fig. 3). Speckle tracking two-dimensional echocardiography strain analysis technology confirmed left ventricular thrombosis, and also revealed decreased movement of the inferior and posterior walls, the basal segment of the posterior wall was locally fibrotic (Fig. 4A and B). Further, myocardial contrast echocardiography confirmed left ventricular thrombosis (Fig. 4C). Cardiovascular magnetic resonance imaging indicated biventricular uneven hypertrophy, which was considered metabolic cardiomyopathy, with diffuse fibrosis of biventricular walls, apical thrombosis, and ischemic cardiomyopathy in the basal segment of the left ventricular lateral wall and left ventricular anterior wall (Fig. 5). Serum alphagalactosidase concentration was 0.7 nmol/h/mgPr (normal range, 29.0-64.4 nmol/h/mgPr). Subsequent genetic testing revealed that he was hemizygous for a previously reported missense mutation (c.902G>A) inexon 6 of the GLA gene, [1] which induce p. R301Q (p.Arg301Gln), confirming a diagnosis of FD (Fig. 6).Interventions: Orally administered drugs included rivaroxaban, sacubitril valsartan, beta blockers, dapagliflozin, and mineralocorticoid receptor antagonist. Cardiac resynchronization therapy with an implanted defibrillator was implemented to prevent sudden death.Outcomes: At present, he is still in follow-up and there have been no adverse events. Conclusion:Our case suggests that clinicians should consider the possibility of FD in patients with acute myocardial infarction and cardiomyopathy. A detailed analysis of subtle historical clues would help promote earlier diagnosis of FD.

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Section: Discussionmentioning

confidence: 75%

Fabry disease with acute myocardial infarction, left ventricular thrombosis, and pericardial effusion

Zhou

Wang

et al. 2022

Medicine

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“…Classic FD symptoms normally present during early childhood but can be delayed in heterozygous cases. A late onset phenotype (i.e., cardiac variants) presents chiefly cardiac involvements, especially LVH, as a primary sign after the fourth decade of life [ 3 , 5 , 11 , 12 ]. The disease course of this phenotype is still largely unknown but tends to develop severe cardiac diseases in elderly individuals [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Unexplained Left Ventricular Hypertrophy with Symptomatic High-Grade Atrioventricular Block in Elderly Patients: A Case Report

Chen

2022

JCM

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Left ventricular hypertrophy (LVH) is common among older adults. Amidst all causes, Fabry disease (FD) should be considered when LVH occurs with family history, specific clinical manifestations, or cardiac alert signs. Here, we report a case of a 76-year-old male who presented late onset concentric LVH with symptomatic high-grade atrioventricular (AV) block. After dual-chamber pacemaker implantation, interrogation revealed frequent right ventricular (RV) pacing with a wide QRS duration. The patient developed heart failure symptoms with rapid deterioration of LV systolic function. Pacing-induced cardiomyopathy (PICM) was suspected, and the pacemaker was upgraded to biventricular pacing. Further FD surveys were performed, including biochemical examinations, cardiac biopsies, and genetic sequencing, and the patient was ultimately diagnosed with a cardiac variant of FD. Particularly, we strongly suggest that physiologic pacing should be initially considered for patients with FD who have symptomatic high-grade AV block, rather than traditional RV pacing to prevent PICM.

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“…The most common variant detected in the screening was IVS4+919G>A in Hong Kong and Japan, with a total of 11 individuals carrying this variant [82,92,97]. This variant was frequently detected in NBS in Taiwan and patients with late-onset FD with cardiac manifestations [17].…”

Section: High-risk Screening For Fd In Individuals With Cardiac Manifestationsmentioning

confidence: 98%

“…We reviewed 23 high-risk screenings for FD in individuals with cardiac manifestations (Table 2), with 20 screenings performed for individuals with either LVH or HCM [40,[80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98]. The other three screenings were performed in individuals with a variety of cardiac symptoms, including coronary artery disorders, conduction disorders, cardiomyopathy, and valvular disease [99], those with conduction disorders requiring a pacemaker [100], and those with left ventricular noncompaction (LVNC) [101].…”

Section: High-risk Screening For Fd In Individuals With Cardiac Manifestationsmentioning

confidence: 99%

“…This might be due to the higher frequency of variants, such as IVS4+919G>A and p.N215S, which tend to develop cardiac manifestations. Although most screenings in individuals with LVH or HCM excluded individuals with hypertension and valvular disease, Fan et al [82] detected IVS4+919G>A in individuals with LVH and hypertension or valvular disease and insisted that manifestations, such as hypertension and valvular disease, should not be excluded. Conversely, screening in individuals with manifestations other than LVH or HCM, such as conduction disturbances and LVNC, did not detect many GLA pathogenic variants.…”

Section: High-risk Screening For Fd In Individuals With Cardiac Manifestationsmentioning

confidence: 99%

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High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review

et al. 2021

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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 screening in patients with renal, cardiac, and central neurological manifestations. Based on the results of this study and review of research abroad, we believe that FD can be detected more effectively by targeting individuals based on age. In recent years, the methods for high-risk screening have been ameliorated, and high-risk screening studies using GLA next-generation sequencing have been conducted. Considering the cost-effectiveness of screening, GLA sequencing should be performed in individuals with reduced α-Gal A activity and females with certain FD manifestations and/or a family history of FD. The findings suggest that family analysis would likely detect FD patients, although GLA sequencing of asymptomatic family members requires adequate genetic counseling.

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High Prevalence of Late-Onset Fabry Cardiomyopathy in a Cohort of 499 Non-Selective Patients with Left Ventricular Hypertrophy: The Asian Fabry Cardiomyopathy High-Risk Screening Study (ASIAN-FAME)

Cited by 7 publications

References 30 publications

Fabry disease with acute myocardial infarction, left ventricular thrombosis, and pericardial effusion

Fabry disease with acute myocardial infarction, left ventricular thrombosis, and pericardial effusion

Unexplained Left Ventricular Hypertrophy with Symptomatic High-Grade Atrioventricular Block in Elderly Patients: A Case Report

High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review

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