The clinical spectrum of Fabry disease, an X-linked lysosomal storage disorder due to alpha-galactosidase A (alpha-Gal A) deficiency, has been expanded beyond the classic phenotype to include the recently recognized later-onset "cardiac" and "renal" variants. The clinical manifestations in each of these disease subtypes are presented with particular emphasis on early recognition among pediatric patients as well as identification of unrecognized patients diagnosed as hypertrophic cardiomyopathy or in renal dialysis clinics. Previously, treatment of patients with Fabry disease was limited to palliative care of the excruciating pain, cardiac and cerebrovascular manifestations, and renal failure. Recently, Fabry-specific enzyme replacement therapy (ERT) with recombinant alpha-Gal A (Fabrazyme) has proven safe and effective. The preclinical, Phase 1/2 and multicenter, double-blind, randomized, placebo-controlled Phase 3 and 4 trials provided the evidence for the safety and efficacy of Fabrazyme treatment. The preclinical and Phase 1/2 studies demonstrated that enzyme delivery to various tissues and GL-3 clearance were dose-dependent. The Phase 3 clinical trial and 3-year extension study provided long-term data documenting the safety and effectiveness of 1 mg/kg of Fabrazyme for this disease. Finally, the "top-line" data from the Phase 4 trial indicates that in patients with mildly to moderately advanced renal disease, Fabrazyme can slow the progression of renal, cardiac, and cerebrovascular events taken together or individually. The Phase 4 trial results also emphasize the importance of early treatment. In sum, these clinical trials provide the evidence-based safety and efficacy of Fabrazyme replacement therapy for Fabry disease.
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Urologie
January 2025
Universitätsklinik für Urologie, Universität Bern, Inselspital Bern, Bern, Schweiz.
Background: Recent studies have also shown that clinical monitoring of quality of life (HRQoL) helps to recognize kidney transplant failure at an early stage.
Objectives: Given the potential of improving HRQoL for the long-term outcomes of kidney transplantation, we conducted a rapid review of the last 5 years of quality of life evaluation after adult allogeneic kidney transplantation.
Materials And Methods: A rapid evidence analysis was carried out using a literature search in MEDLINE in the period 2019-2024.
Kardiol Pol
January 2025
Department of Cardiology and Electrotherapy, Silesian Center for Heart Diseases, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.
Circ Cardiovasc Imaging
January 2025
Multimodality Cardiac Imaging Section, IRCCS Policlinico San Donato, Milan, Italy (L.T., G.D., M.L., A.C.).
J Magn Reson Imaging
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ImageWorks LLC, Shaker Heights, Ohio, USA.
Stem Cell Res
January 2025
Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Ji'nan 250014 Shandong, China; Biomedical Sciences College, Shandong Medicinal Biotechnology Centre, Shandong First Medical University& Shandong Academy of Medical Sciences, Ji'nan 250062 Shandong, China; Key Lab for Biotech-Drugs of National Health Commission, Ji'nan 250062 Shandong, China; Key Lab for Rare & Uncommon Diseases of Shandong Province, Ji'nan 250062 Shandong, China. Electronic address:
Fabry disease (FD) is a systemic disease in which globotriaosylceramide and other naturally occurring glycosphingolipid accumulate in various tissues throughout the body due to mutation of α-galactosidase A (GLA). These induced pluripotent stem cells (iPSCs) were generated from a 10-year-old male patient's urine carrying the GLA c.1080_1082del Fabry disease mutation.
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