美国Hunter结局调查中黏多糖贮积症II型患者的临床特征与管理

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中文摘要

背景： 2022年，黏多糖贮积症II型（MPS II）被列入美国推荐纳入新生儿筛查面板的疾病清单；预计这将大幅促进更早诊断和治疗并改善患者结局。对Hunter结局调查（HOS）注册研究中入组的美国患者进行了分析，以支持在这一重要时刻更新对美国人群中MPS II及其管理的认识。
结果： 美国队列包括326例MPS II患者（症状发作和诊断的中位年龄分别为1.5岁和3.0岁）。在有基因型数据的患者中，超过一半（50.9%）在艾杜糖醛酸-2-硫酸酯酶基因中具有错义变异。最常报告的疾病表现是关节僵硬（52.5%）和粗陋面容（51.8%），其中慢性中耳炎是最早出现的体征（中位出现年龄为1.2岁）。大多数患者（88.7%）接受了至少一剂酶替代治疗（ERT），在有可用数据的患者中超过一半在6岁前开始治疗（160/289；55.4%）；44/289例患者（15.2%）在18个月龄前开始治疗。218/219例患者（99.5%）报告了手术；最常见的是port-a-cath置入或更换（53.0%）；最早常见的手术是扁桃体切除术（首次手术的中位年龄为2.7岁）。有166例患者可获得5岁后认知状态的数据，其中73例（44.0%）存在认知障碍。认知障碍患者的症状发作和诊断中位年龄（分别为1.0岁和2.5岁）略低于无认知障碍患者（分别为3.0岁和4.0岁）。不同种族亚组与总体队列之间大多数疾病特征相似，尽管与白人患者相比，认知障碍在代表性不足的患者群体中数量上更为普遍。
结论： 这些来自HOS的数据提供了对美国MPS II特征及其管理的最新全面认识，预计将在实施新生儿筛查的同时为临床决策提供信息。在认知障碍患者与无认知障碍患者之间发现的代表性不足群体患者比例的差异，凸显了继续促进研究、检测和可及性多样性的持续需求。

英文摘要

BACKGROUND: In 2022, mucopolysaccharidosis II (MPS II) was added to the list of disorders recommended for inclusion in newborn screening panels in the USA; this is expected to substantially facilitate earlier diagnosis and treatment and improve patient outcomes. An analysis was conducted in US patients enrolled in the Hunter Outcome Survey (HOS) registry, to support the need for an updated understanding of MPS II and its management in the US population at this important juncture.
RESULTS: The US cohort comprised 326 patients with MPS II (median ages at symptom onset and at diagnosis of 1.5 year and 3.0 years, respectively). Of the patients for whom genotype data were available, over half (50.9%) had a missense variant in the iduronate-2-sulfatase gene. The most commonly reported disease manifestations were joint stiffness (52.5%) and coarse facial features (51.8%), with chronic otitis media being the earliest presenting sign (presenting at a median age of 1.2 years). Most patients (88.7%) received at least one dose of enzyme replacement therapy (ERT), and more than half of patients for whom there were available data started treatment before 6 years of age (160/289; 55.4%); 44/289 patients (15.2%) started treatment before 18 months of age. Surgery was reported in 218/219 patients (99.5%); the most common was port-a-cath placement or replacement (53.0%); the earliest common surgery was tonsillectomy (first surgery at a median age of 2.7 years). Data on cognitive status after 5 years of age were available for 166 patients, of whom 73 (44.0%) had cognitive impairment. Median ages at symptom onset and at diagnosis in patients with cognitive impairment (1.0 year and 2.5 years, respectively) were slightly lower than those for patients without cognitive impairment (3.0 years and 4.0 years, respectively). Most disease characteristics were similar between different racial subgroups and the overall cohort, although cognitive impairment was numerically more prevalent among underrepresented patient groups compared with White patients.
CONCLUSIONS: These data from HOS provide an updated comprehensive insight into the characteristics of MPS II and its management in the USA and are expected to inform clinical decision-making alongside the implementation of newborn screening. Differences identified in the proportion of patients from underrepresented groups between those with cognitive impairment and those without highlight the continued need to promote diversity in research, detection and access.