The Diagnostic and Therapeutic Challenges of Fabry Nephropathy—A Review of the Literature, Illustrated by a Clinical Case DOI Open Access
Stefan Van Cauwelaert, Caroline Geers,

Dominique Vandervelde

et al.

Open Journal of Nephrology, Journal Year: 2023, Volume and Issue: 13(04), P. 349 - 368

Published: Jan. 1, 2023

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 Nephropathy (FN), can vary mild proteinuria kidney failure. FN diagnosis, especially cases with genetic Variant of Unknown Significance (VUS) the GLA gene, poses challenges. Measurement plasma lyso-Gb3 levels gaining importance while renal biopsy electron microscopy remains gold standard equivocal cases. Treatment options include Enzyme Replacement Therapy (ERT) and chaperone therapy, demanding careful candidate selection due high treatment costs. Research has predominantly focused on FD, revealing modest benefits. However, evidence for treating patients, females, phenotypes scarce, emphasizing necessity placebo-controlled trials these subgroups. Meanwhile, participation global FD registries improve our understanding disease management. Case Presentation: woman her late sixties presented moderate chronic disease, proteinuria, microscopic hematuria. Her family history included prevalence renal, cardiac cerebrovascular diseases. Kidney revealed characteristic myelin figures zebra bodies podocytes, strongly suggestive FN. Genetic analysis identified VUS gene (c.655A > C, p.Ile219Leu), introducing diagnostic uncertainty. Further investigations involvement. Considering recurring difficulty finding during assessments, along uncertainty regarding need phenotypes, women, this case becomes central focus thorough review literature. This aims propose practical algorithm that integrates clinical, biochemical, markers screening diagnosis. Additionally, it explores benefits female patients.

Language: Английский

Treatment of Fabry Disease: Established and Emerging Therapies DOI Creative Commons
Muhammad Umer,

Dinesh Kalra

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 320 - 320

Published: Feb. 20, 2023

Fabry disease (FD) is a rare, X-linked inherited disorder of glycosphingolipid metabolism. It leads to the progressive accumulation globotriaosylceramide within lysosomes due deficiency α-galactosidase A enzyme. involves multiple organs, predominantly renal, cardiac, and cerebrovascular systems. Early diagnosis treatment are critical prevent progression irreversible tissue damage organ failure, halt life-threatening complications that can significantly reduce life expectancy. This review will focus on established emerging options for FD.

Language: Английский

Citations

19
Fabry Disease: Switch from Enzyme Replacement Therapy to Oral Chaperone Migalastat: What Do We Know Today? DOI Open Access
Fernando Perretta, Sebastián Jaurretche

Healthcare, Journal Year: 2023, Volume and Issue: 11(4), P. 449 - 449

Published: Feb. 4, 2023

Fabry disease is a lysosomal storage disorder caused by the deficiency of α-galactosidase-A enzyme. The result progressive accumulation complex glycosphingolipids and cellular dysfunction. Cardiac, renal, neurological involvement significantly reduces life expectancy. Currently, there increasing evidence that clinical response to treatment improves with early timely initiation. Until few years ago, options for were limited enzyme replacement therapy agalsidase alfa or beta administered intravenous infusion every 2 weeks. Migalastat (Galafold®) an oral pharmacological chaperone increases activity "amenable" mutations. safety efficacy migalastat supported in phase III FACETS ATTRACT studies, compared available therapies, showing reduction left ventricular mass, stabilization kidney function plasma Lyso-Gb3. Similar results confirmed subsequent extension publications, both patients who started as their first previously on switched migalastat. In this review we describe switching from mutations, referring publications date.

Language: Английский

Citations

11
A Multi-Omics-Empowered Framework for Precision Diagnosis and Treatment of Lysosomal Diseases DOI Creative Commons
Nguyen Thi Hai Yen,

Nguyen Tran Nam Tien,

Nguyen Quang Thu

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101274 - 101274

Published: March 1, 2025

Language: Английский

Citations

0
Safety and efficacy of migalastat in adolescent patients with Fabry disease: Results from ASPIRE, a phase 3b, open-label, single-arm, 12-month clinical trial, and its open-label extension DOI Creative Commons
Uma Ramaswami, Esperanza Font–Montgomery, Özlem Göker-Alpan

et al.

Molecular Genetics and Metabolism, Journal Year: 2025, Volume and Issue: 145(1), P. 109102 - 109102

Published: April 4, 2025

Language: Английский

Citations

0
Progress and Challenges in the Treatment of Fabry Disease DOI Creative Commons
Malte Lenders,

Elise Raphaela Menke,

Eva Brand

et al.

BioDrugs, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Fabry disease is a rare but life-threatening, X-linked, inherited lysosomal storage disorder in which globotriaosylceramide insufficiently metabolized because of reduced α-galactosidase A activity. Cellular accumulation causes multisystemic disease, which, if left untreated, reduces life expectancy female and male individuals by around 10 20 years, respectively, leading to progressive renal failure, hypertrophic cardiomyopathy, cardiac arrhythmia, premature cerebral infarction. The method choice for confirming the diagnosis determination activity leukocytes molecular genetic detection disease-causing mutation individuals. Current approved treatment includes enzyme replacement therapy (agalsidase alfa [0.2 mg/kg body weight], agalsidase beta or pegunigalsidase [both 1.0 weight]) every other week intravenously or, responding ('amenable') present, oral pharmacological chaperone (migalastat 123 mg, day). Future therapeutic options may include substrate reduction therapy, gene messenger RNA and/or vesicle-packaged therapy. This review presents current future with advantages disadvantages different options.

Language: Английский

Citations

0
Real-world clinical outcomes in adult patients with Fabry disease: A 20-year retrospective observational cohort study from a single centre DOI
Éamon P. McCarron, Rajkumar Chinnadurai, Jonathan M. Meyer

et al.

Molecular Genetics and Metabolism Reports, Journal Year: 2025, Volume and Issue: 43, P. 101229 - 101229

Published: May 14, 2025

Language: Английский

Citations

0
Renal and multisystem effectiveness of 3.9 years of migalastat in a global real‐world cohort: Results from the followME Fabry Pathfinders registry DOI Creative Commons
Derralynn Hughes, Gere Sunder‐Plassmann, Ana Jovanović

et al.

Journal of Inherited Metabolic Disease, Journal Year: 2024, Volume and Issue: 48(1)

Published: July 19, 2024

Abstract Fabry disease is a progressive, X‐linked lysosomal disorder caused by reduced or absent α‐galactosidase A activity due to GLA variants. The effects of migalastat were examined in cohort 125 patients with migalastat‐amenable variants the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient‐focused evaluating outcomes for current treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry‐associated clinical events (FACEs) who had received ≥3 years treatment real‐world setting. As August 2022, (60% male) mean exposure 3.9 years. At enrolment, median age was 58 (males, 57; females, 60) eGFR 83.7 mL/min/1.73 m 2 ( n = 122; males, 83.7; 83.8) left ventricular mass index 115.1 g/m 61; 131.2; 98.0). Mean (95% confidence interval) change overall 116) −0.9 (−10.8, 9.9) /year similar observed across varying levels kidney function at enrolment. Despite population baseline morbidity, 80% did not experience FACE during exposure. incidence renal, cardiac, cerebrovascular 2.0, 83.2, 4.1 per 1000 patient‐years, respectively. These data support role preserving renal multisystem effectiveness this population.

Language: Английский

Citations

3
Updated Evaluation of Agalsidase Alfa Enzyme Replacement Therapy for Patients with Fabry Disease: Insights from Real-World Data DOI Creative Commons
Sandro Feriozzi,

Cristina Chimenti,

Ricardo Reisin

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 1083 - 1101

Published: April 1, 2024

The clinical use of agalsidase alfa as enzyme replacement therapy (ERT) for Fabry disease (FD) has spread since 2001, and a large body evidence its effectiveness been collected.This review presents the laboratory results achieved with alfa, which published in literature.Agalsidase infusion slows down or stops progression renal damage, expressed by reduction stabilization annual decline glomerular filtration rate; yearly decrease rate (slope) sometimes is reduced until stabilization.ERT prevents reduces occurrence hypertrophic cardiomyopathy increase over time if it already present.Moreover, regarding neurological manifestations, ERT improves neuropathic pain quality life, recent data indicated that may also prevent burden cerebrovascular disease.In addition to ERT's benefits, crucial topics like most appropriate start role anti-drug antibodies (ADA) are analyzed.Treatment patients FD substantially their outcomes enhances life FD.

Language: Английский

Citations

2
Inherited kidney disease and CAKUT are common causes of kidney failure requiring kidney replacement therapy: an ERA Registry study DOI Creative Commons
Alberto Ortíz, Anneke Kramer, Gema Ariceta

et al.

Nephrology Dialysis Transplantation, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

ABSTRACT Background Inherited kidney diseases (IKDs) and congenital anomalies of the urinary tract (CAKUT) are causes failure requiring replacement therapy (KRT) that major renal registries usually amalgamate into primary disease(PRD) category ‘miscellaneous’ or in glomerulonephritis pyelonephritis categories. This makes IKDs invisible (except for polycystic disease) may negatively influence use genetic testing, which identify a cause some CAKUT. Methods We re-examined aetiology KRT by composing separate IKD CAKUT PRD group using data from European Renal Association (ERA) Registry. Results In 2019, IKD-CAKUT was fourth most common among incident patients, accounting 8.9% cases [IKD 7.4% (including 5.0% autosomal dominant disease), 1.5%], behind diabetes (23.0%), hypertension (14.4%) (10.6%). patients <20 years age (41.0% cases), but their incidence rate highest those ages 45–74 (22.5 per million age-related population). Among prevalent (18.5%) (18.7%) were two overall, while women (21.6%) <45 (29.1%). Conclusion patients. Distinct categorization better characterizes epidemiology chronic disease (CKD) highlights importance testing diagnostic workup CKD.

Language: Английский

Citations

2
Fabry nephropathy: a treatable cause of chronic kidney disease DOI Open Access
Michael L. West, Laurette Geldenhuys, Daniel G. Bichet

et al.

Rare Disease and Orphan Drugs Journal, Journal Year: 2024, Volume and Issue: 3(3)

Published: July 11, 2024

Fabry disease is a rare X-linked inborn error of metabolism that has high prevalence chronic kidney (CKD) and renal failure. It due to the deficiency α-galactosidase A (α-Gal) lysosomal enzyme with subsequent accumulation globotriaosylceramide (Gb3) in lysosomes. In kidney, podocyte main target this disease, although all cell types are involved. The podocyte, being terminally differentiated, does not replicate thus accumulates Gb3 throughout life. Podocytes injured by Gb3, leading their detachment from glomerular basement membrane loss urine. Albuminuria starts childhood progresses overt proteinuria teens 20 s. CKD ensues adults starting dialysis at an average age 42 years. Patients have stroke cardiomyopathy hypertrophic change, heart failure, dysrhythmias. Patient survival limited both genders. Diagnosis based on demonstration low α-Gal activity pathogenic GLA mutation. Clinical features highly variable, which makes recognition condition difficult. Treatment intravenous recombinant human replacement therapy (ERT) oral pharmacologic chaperone available. Control 0.5 g/day or less critical importance limit progression end-stage disease. Early initiation treatment gives best results, but optimal start uncertain. nephropathy remains challenge its multisystem nature, difficult diagnosis, complicated management. important as treatable cause CKD.

Language: Английский

Citations

2