Natural history of valve disease in patients with mucopolysaccharidosis II and the impact of enzyme replacement therapy.

Autor: Kampmann C; Department of Pediatric Cardiology and Structural Heart Diseases, Center for Diseases in Childhood and Adolescence, University Medicine Mainz, Mainz, Germany., Lampe C; Department of Child Neurology, Epileptology and Social Medicine, University Hospital Giessen, Giessen, Germany., Wiethoff CM; Department of Pediatric Cardiology and Structural Heart Diseases, Center for Diseases in Childhood and Adolescence, University Medicine Mainz, Mainz, Germany., Arash-Kaps L; SphinCS, Institute of Clinical Science in LSD, Hochheim, Germany., Mengel E; SphinCS, Institute of Clinical Science in LSD, Hochheim, Germany., Reinke J; Medical center for adults with disabilities, Kreuznacher Diakonie, Bad Kreuznach, Germany., Beck M; SphinCS, Institute of Clinical Science in LSD, Hochheim, Germany., Hennermann JB; Department of Metabolic Diseases, Villa Metabolica, Center for Diseases in Childhood and Adolescence, University Medicine Mainz, Mainz, Germany., Abu-Tair T; Department of Pediatric Cardiology and Structural Heart Diseases, Center for Diseases in Childhood and Adolescence, University Medicine Mainz, Mainz, Germany.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2024 Oct 23. Date of Electronic Publication: 2024 Oct 23.
DOI: 10.1002/jimd.12808
Abstrakt: Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare, X-linked lysosomal storage disease caused by reduced activity of iduronate-2-sulfatase (I2S), with subsequent cellular accumulation of the glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate (DS). DS is a major component of the extracellular matrix of heart valves, which can be affected in MPS II. We investigated the natural history of valve disease in MPS II and the impact of long-term intravenous enzyme replacement therapy (ERT) with recombinant I2S (idursulfase). In total, 604 cardiac examinations were assessed from serial follow-up of 80 male patients (49 neuronopathic). Valve disease was classified according to standard practice from hemodynamic features evident from echocardiography. The natural history group comprised 48 patients (up to 14.8 years of follow-up; median, 2.6 years; 24 patients started ERT during the study); 56 patients were treated (up to 14.2 years of follow-up; median, 6.2 years). Lifetime GAG burden (calculated from urinary GAG measurements) correlated significantly with the degree of valve disease. Onset of moderate-to-severe valve disease was significantly delayed in treated (median age at onset, 29.1 ± 2 [95% CI: 25.2-32.9] years; Kaplan-Meier estimation) versus untreated patients (17.6 ± 1 [95% Cl: 15.8-19.4] years; p < 0.0001). Cox regression modeling found that long-term ERT reduced the probability of developing severe valve disease (χ 2 , 32.736; significant after 5 years of ERT). Overall, this study found that valve disease severity in MPS II correlates with GAG burden and that progression is delayed by long-term ERT.
(© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
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