Fabry disease (FD) is a rare X-linked lysosomal accumulation disorder caused by a deficiency in the enzyme alpha-galactosidase A (Gal A), resulting in excessive storage of glycosphingolipids, particularly globotriaosy...Fabry disease (FD) is a rare X-linked lysosomal accumulation disorder caused by a deficiency in the enzyme alpha-galactosidase A (Gal A), resulting in excessive storage of glycosphingolipids, particularly globotriaosylceramide (Gb3). This leads to cellular dysfunction in various organs, with cardiovascular compromise being the major cause of morbidity and mortality. This study aimed to provide a comprehensive overview of FD focusing on its genetic, epidemiological, clinical, diagnostic, and therapeutic aspects. This study explored the genetic mutations associated with FD, its epidemiology, clinical phenotypes, cardiac manifestations, diagnostic approaches, and current treatment options. Background: FD is caused by mutations in GLA on the X chromosome, with over 1000 identified variants. Neonatal screening and specific studies have shown an increased incidence of FD. The clinical presentation varies between classic and late phenotypes, with cardiac involvement being a major concern, particularly in late-onset FD. Purpose: This study aimed to summarize the current knowledge on FD, emphasizing cardiac involvement, diagnostic modalities, and treatment options. Methods: A literature review of relevant studies on FD, including genetics, epidemiology, clinical presentation, diagnostic methods, and treatment options, was conducted. Results: Cardiac manifestations of FD included left ventricular hypertrophy (LVH), heart failure, arrhythmias, and sudden death. Diagnostic approaches such as electrocardiography, echocardiography, and cardiac magnetic resonance imaging play crucial roles in the early detection and monitoring of cardiac involvement. Enzyme replacement therapy (ERT) and emerging treatments have shown promise in managing FD, although challenges remain. Conclusions: FD remains a challenging condition in cardiology, with under-diagnosis being a concern. Early detection and specific therapy are essential to improve patient outcomes. Echocardiography and cardiac MRI are valuable tools for diagnosis and follow-up. De展开更多
Fabry Disease (FD) is a rare lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) enzyme deficiency, resulting in glycosphingolipid accumulation. Its clinical spectrum ranges from severe classical...Fabry Disease (FD) is a rare lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) enzyme deficiency, resulting in glycosphingolipid accumulation. Its clinical spectrum ranges from severe classical to milder nonclassical or late-onset phenotypes. Renal involvement, termed Fabry Nephropathy (FN), can vary from mild proteinuria to kidney failure. FN diagnosis, especially in nonclassical cases with a genetic Variant of Unknown Significance (VUS) in the GLA gene, poses challenges. Measurement of plasma lyso-Gb3 levels is gaining importance in FN diagnosis, while renal biopsy with electron microscopy remains the gold standard in equivocal cases. Treatment options include Enzyme Replacement Therapy (ERT) and chaperone therapy, demanding careful candidate selection due to high treatment costs. Research has predominantly focused on classical FD, revealing modest treatment benefits. However, evidence for treating patients, especially females, with milder nonclassical or late-onset phenotypes is scarce, emphasizing the necessity for placebo-controlled clinical trials in these subgroups. Meanwhile, participation in global FD registries can improve our understanding of disease management. Case Presentation: A woman in her late sixties presented with moderate chronic kidney disease, mild proteinuria, and microscopic hematuria. Her family history included a prevalence of renal, cardiac and cerebrovascular diseases. Kidney biopsy revealed characteristic myelin figures and zebra bodies in podocytes, strongly suggestive of FN. Genetic analysis identified a VUS in the GLA gene (c.655A > C, p.Ile219Leu), introducing diagnostic uncertainty. Further investigations revealed severe cardiac involvement. Considering the recurring difficulty presented by the finding of a VUS in the GLA gene during FN assessments, along with the uncertainty regarding the need for treatment in nonclassical or late-onset FD phenotypes, especially in women, this case becomes a central focus for a thorough review of the literature. This rev展开更多
文摘Fabry disease (FD) is a rare X-linked lysosomal accumulation disorder caused by a deficiency in the enzyme alpha-galactosidase A (Gal A), resulting in excessive storage of glycosphingolipids, particularly globotriaosylceramide (Gb3). This leads to cellular dysfunction in various organs, with cardiovascular compromise being the major cause of morbidity and mortality. This study aimed to provide a comprehensive overview of FD focusing on its genetic, epidemiological, clinical, diagnostic, and therapeutic aspects. This study explored the genetic mutations associated with FD, its epidemiology, clinical phenotypes, cardiac manifestations, diagnostic approaches, and current treatment options. Background: FD is caused by mutations in GLA on the X chromosome, with over 1000 identified variants. Neonatal screening and specific studies have shown an increased incidence of FD. The clinical presentation varies between classic and late phenotypes, with cardiac involvement being a major concern, particularly in late-onset FD. Purpose: This study aimed to summarize the current knowledge on FD, emphasizing cardiac involvement, diagnostic modalities, and treatment options. Methods: A literature review of relevant studies on FD, including genetics, epidemiology, clinical presentation, diagnostic methods, and treatment options, was conducted. Results: Cardiac manifestations of FD included left ventricular hypertrophy (LVH), heart failure, arrhythmias, and sudden death. Diagnostic approaches such as electrocardiography, echocardiography, and cardiac magnetic resonance imaging play crucial roles in the early detection and monitoring of cardiac involvement. Enzyme replacement therapy (ERT) and emerging treatments have shown promise in managing FD, although challenges remain. Conclusions: FD remains a challenging condition in cardiology, with under-diagnosis being a concern. Early detection and specific therapy are essential to improve patient outcomes. Echocardiography and cardiac MRI are valuable tools for diagnosis and follow-up. De
文摘Fabry Disease (FD) is a rare lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) enzyme deficiency, resulting in glycosphingolipid accumulation. Its clinical spectrum ranges from severe classical to milder nonclassical or late-onset phenotypes. Renal involvement, termed Fabry Nephropathy (FN), can vary from mild proteinuria to kidney failure. FN diagnosis, especially in nonclassical cases with a genetic Variant of Unknown Significance (VUS) in the GLA gene, poses challenges. Measurement of plasma lyso-Gb3 levels is gaining importance in FN diagnosis, while renal biopsy with electron microscopy remains the gold standard in equivocal cases. Treatment options include Enzyme Replacement Therapy (ERT) and chaperone therapy, demanding careful candidate selection due to high treatment costs. Research has predominantly focused on classical FD, revealing modest treatment benefits. However, evidence for treating patients, especially females, with milder nonclassical or late-onset phenotypes is scarce, emphasizing the necessity for placebo-controlled clinical trials in these subgroups. Meanwhile, participation in global FD registries can improve our understanding of disease management. Case Presentation: A woman in her late sixties presented with moderate chronic kidney disease, mild proteinuria, and microscopic hematuria. Her family history included a prevalence of renal, cardiac and cerebrovascular diseases. Kidney biopsy revealed characteristic myelin figures and zebra bodies in podocytes, strongly suggestive of FN. Genetic analysis identified a VUS in the GLA gene (c.655A > C, p.Ile219Leu), introducing diagnostic uncertainty. Further investigations revealed severe cardiac involvement. Considering the recurring difficulty presented by the finding of a VUS in the GLA gene during FN assessments, along with the uncertainty regarding the need for treatment in nonclassical or late-onset FD phenotypes, especially in women, this case becomes a central focus for a thorough review of the literature. This rev
