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

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Christoph Kampmann, Christina Lampe, Christiane M Wiethoff, Laila Arash-Kaps, Eugen Mengel, Joerg Reinke, Michael Beck, Julia B Hennermann, Tariq Abu-Tair
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Abstract

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 (χ2, 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.

黏多醣症 II 患者瓣膜疾病的自然病程以及酶替代疗法的影响。
粘多糖病 II(MPS II,亨特综合征)是一种罕见的 X 连锁溶酶体贮积病,其病因是伊度酸-2-硫酸酯酶(I2S)活性降低,导致糖胺聚糖(GAGs)、硫酸肝素和硫酸真皮酯(DS)在细胞内蓄积。DS 是心脏瓣膜细胞外基质的主要成分,在 MPS II 中也会受到影响。我们研究了 MPS II 患者瓣膜疾病的自然史,以及长期静脉注射重组 I2S(idursulfase)酶替代疗法(ERT)的影响。我们对 80 名男性患者(49 名神经病变患者)进行了连续随访,共评估了 604 次心脏检查结果。根据超声心动图显示的血流动力学特征,按照标准做法对瓣膜疾病进行分类。自然病史组包括48名患者(随访时间长达14.8年;中位数为2.6年;24名患者在研究期间开始接受ERT治疗);56名患者接受了治疗(随访时间长达14.2年;中位数为6.2年)。终生 GAG 负担(通过尿液 GAG 测量值计算)与瓣膜病变程度显著相关。与未接受治疗的患者(17.6 ± 1 [95% Cl:15.8-19.4]岁;P 2,32.736;接受 ERT 5 年后显著)相比,接受治疗的患者中度至重度瓣膜病的发病时间明显推迟(发病年龄中位数为 29.1 ± 2 [95% CI:25.2-32.9]岁;Kaplan-Meier 估计值)。总之,这项研究发现,MPS II 的瓣膜疾病严重程度与 GAG 负担相关,长期 ERT 可延缓病情发展。
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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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