Early start of enzyme replacement therapy in pediatric male patients with classical Fabry disease is associated with attenuated disease progression.

Autor: van der Veen SJ; Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Lysosome Center 'Sphinx', Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands., Körver S; Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Lysosome Center 'Sphinx', Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands., Hirsch A; Department of Cardiology and Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Room Rg-419, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands., Hollak CEM; Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Lysosome Center 'Sphinx', Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands., Wijburg FA; Amsterdam UMC, University of Amsterdam, Department of Pediatric Metabolic Diseases, Emma Children's Hospital, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Lysosome Center 'Sphinx', Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands., Brands MM; Amsterdam UMC, University of Amsterdam, Department of Pediatric Metabolic Diseases, Emma Children's Hospital, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Lysosome Center 'Sphinx', Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands., Tøndel C; Haukeland University Hospital, Department of Paediatrics and University of Bergen, Department of Clinical Medicine, Bergen, Norway., van Kuilenburg ABP; Amsterdam UMC, University of Amsterdam, Department of Clinical Chemistry, Gastroenterology & Metabolism, Laboratory Genetic Metabolic Diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands., Langeveld M; Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Lysosome Center 'Sphinx', Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: m.langeveld@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2022 Feb; Vol. 135 (2), pp. 163-169. Date of Electronic Publication: 2021 Dec 17.
DOI: 10.1016/j.ymgme.2021.12.004
Abstrakt: Background: Enzyme replacement therapy (ERT) slows disease progression of Fabry disease (FD), especially when initiated before the onset of irreversible organ damage. However, with the clinically asymptomatic progression of renal, cardiac and cerebral disease manifestations spanning decades, optimal timing of ERT initiation remains unclear.
Methods: In this cross-sectional retrospective study, seven male FD patients with a classical disease phenotype (cFD) who started treatment with agalsidase-beta in childhood were evaluated after 10 years of treatment (median age at evaluation 24 years, range 14-26). Cardiac imaging (echocardiography and MRI), electrophysiological and biochemical data of these patients were compared to those of untreated male cFD patients (n = 23, median age 22 years, range 13-27).
Results: Albuminuria was less common and less severe in treated patients (albumin to creatinine ratio, ACR 0-8.8 mg/mmol, median 0.4) compared to untreated patients (ACR 0-248 mg/mmol, median 3.7, p = 0.02). The treated group had a lower left ventricular mass, measured using echocardiography (median 80 g/m 2 versus 94 g/m 2 , p = 0.02) and MRI (median 53 g/m 2 versus 68 g/m 2 , p = 0.02). Myocardial fibrosis was absent in all included patients. eGFR was normal in all treated patients whereas 7/23 (30%) of untreated patients had abnormal eGFR. Cerebral manifestations did not differ.
Conclusions: Start of treatment with ERT before age 16, in male cFD patients is associated with reduced occurrence of renal and cardiac manifestations of FD, as assessed by intermediate endpoints. Confirmation that this approach delays or even prevents renal failure and cardiac events requires another decade of follow-up.
Competing Interests: Declaration of Competing Interest None.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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