MPS Disease Longitudinal Study of Treatment and Outcomes Across the Lifespan

粘多糖沉积症是单基因的、可遗传的溶酶体功能障碍， 进行性多系统器官损伤早期，人们认为MPS的身体表现 开始于童年，但我们现在知道，糖胺聚糖沉积开始于子宫内， 在生命早期，甚至婴儿期就开始治疗，并不能减轻疾病负担。重要的是，虽然 疾病的主要影响因遗传亚型而异，例如MPS I、II和III具有显著的 认知影响，而MPS IV和VI涉及中枢神经系统，不包括 认知-所有的MPS疾病，无论中枢神经系统的负担，包括显着的骨骼， 和器官缺陷，导致终身残疾;这种残疾存在，无论治疗。 目前的疗法在改善这种毁灭性的脑部疾病方面显示出一些效果，但效果甚微。 躯体效应-特别是当它涉及骨骼（骨）和心脏（瓣膜）受累时。为治疗 MPS条件的选择继续增长，并扩大到包括基因治疗，一个系统的，彻底的 在MPS患者的一生中，疾病影响的分类比以往任何时候都更相关。增加 对早期、纵向、描述性数据的需求是新生儿MPS I筛查的出现， 几个国家。那些通过新生儿筛查确定的人提供了一个独特的机会，可以从 从出生开始就患有MPS I的人。这些数据与我们的研究团队收集的数据相结合， 在过去的10年里，提供了最丰富，最完整的数据集，可用于衡量新的 疗法以本文所述的方式添加到数据集，将产生关于如何 在诊断（通过新生儿筛查或其他方式）任何MPS病症后进行治疗。的 溶酶体疾病网络的结构使我们能够将卓越中心的数据按地理位置合并 分散在美国和加拿大，从尽可能广泛的患者中收集交叉表格数据 人口：1。通过疾病亚型量化神经发育的异常和进展率， 2.表征社会，情感和行为概况;与疾病亚型的治疗相关，3。 确定脑形态测量学和白色物质微观结构的异常，以定义发育 疾病亚型的途径，4。量化身体残疾在器官系统中的负担，以及如何 这些残疾影响发展和心理社会功能，5.评估MPS对骨骼的全面影响 和心脏系统，以及6.确定疾病表达的发病模式 通过新生儿筛查发现的Hurler综合征婴儿，以及当前干细胞移植如何导致 与疾病有关的发病率和死亡率。提出的每个目标都将在相互关联的背景下进行评估， 提供详细的多维数据，旨在将系统负荷定义为未来治疗的指标。

The mucopolysaccharidoses are monogenic, heritable disorders of lysosomal malfunction that cause progressive multi-system organ damage. Early on, it was thought that the physical manifestations of MPS commenced in childhood, but we now know that glycosaminoglycan deposition begins in utero and that treatment beginning early in life, even infancy, does not ameliorate the burden of disease. Importantly, while the primary effects of disease vary by genetic subtype—for example MPS I, II, and III come with a significant cognitive impact, while MPS IV and VI, have central nervous system involvement that does not include cognition—all of the MPS disorders, regardless of central nervous system burden, comprise significant skeletal and organ deficits that results in lifelong disability; and that this disability exists regardless of treatment. Current therapies have shown some effect in ameliorating the devastating brain disease, but have had little somatic effect—especially as it relates to skeletal (bone) and cardiac (valve) involvement. As treatment options for the MPS conditions continue to grow, and expand to include gene therapy, a systematic, thorough categorization of disease effect across the lifetime individuals with MPS is more relevant than ever. Adding to the need for early, longitudinal, descriptive data is the advent of newborn screening for MPS I to the panels in several states. Those identified via a newborn screening present a unique opportunity to collect data from individuals with MPS I beginning at birth. This data, in conjunction with that collected by our research team over the last 10 years, provides the richest, most complete dataset available against which to measure new therapy. Adding to the dataset in the ways described here, will lead to specific recommendations on how to proceed therapeutically, after a diagnosis (via newborn screening or otherwise) for any MPS condition. The Lysosomal Disease Network structure allows us to incorporate data from Centers of Excellence geographically dispersed across the US and Canada to collect cross-tabulated data from the widest possible patient population that: 1. Quantifies abnormalities and rates of progression in neurodevelopment by disease subtype, 2. Characterizes social, emotional, and behavioral profiles; correlated with treatment by disease subtype, 3. Determines abnormalities in brain morphometry and white matter microstructure to define developmental pathways by disease subtype, 4. Quantifies the burden of physical disability across organ systems and how those disabilities impact development and psychosocial function, 5. Assess the full impact of MPS on skeletal and cardiac systems across treatment modalities, and 6. Identify the incidence pattern of disease expression of infants with Hurler syndrome identified by newborn screening, and how current stem cell transplant leads to disease-related morbidity and mortality. Every aim presented will be evaluated in context with each other to provide detailed, multi-dimensional data designed to define systematic burden as a measure for future therapy.