MPS Disease Longitudinal Study of Treatment and Outcomes Across the Lifespan

粘多糖病是溶酶体功能障碍的单基因遗传性疾病，可导致 进行性多系统器官损害。早期，人们认为MPS的物理表现 开始于童年，但我们现在知道糖胺多糖的沉积始于子宫，而且 在生命的早期开始治疗，即使是婴儿，也不能减轻疾病的负担。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MPS VI的中枢神经系统参与不包括 认知-所有的MPS障碍，无论中枢神经系统的负担如何，都包括重要的骨骼 以及导致终生残疾的器官缺陷；无论接受何种治疗，这种残疾都存在。 目前的治疗方法在改善这种毁灭性的脑部疾病方面显示出了一些效果，但收效甚微。 躯体效应--尤其是与骨骼(骨骼)和心脏(瓣膜)受累有关时。作为治疗 针对MPS病情的选择不断增加，并扩大到包括基因治疗在内，系统、彻底 对患有MPS的终生个体的疾病影响分类比以往任何时候都更相关。添加到 对早期、纵向、描述性数据的需求是#年专家组对MPS I新生儿筛查的出现。 几个州。那些通过新生儿筛查确认的人提供了一个独特的机会来收集数据 患有MPS I的人从出生起就开始。这些数据与我们研究小组收集的数据相结合 在过去10年中，提供了最丰富、最完整的数据集，可用来衡量新的 心理治疗。以此处所述的方式添加到数据集，将产生有关如何 在诊断出(通过新生儿筛查或其他方式)任何MPS情况后，继续进行治疗。这个 溶酶体疾病网络结构使我们能够在地理位置上整合卓越中心的数据 分散在美国和加拿大，从尽可能广泛的患者那里收集交叉表格数据 人口：1.按疾病亚型量化神经发育的异常和进展速度， 2.描述社会、情绪和行为特征；与疾病亚型治疗相关，3. 确定大脑形态测量和脑白质微结构的异常以确定发育 按疾病亚型分类的途径，4.量化各器官系统的身体残疾负担以及如何 这些残疾影响发育和心理社会功能，5.评估MPS对骨骼的全面影响 和心脏系统，以及6.确定疾病表现的发病模式 通过新生儿筛查确定患有赫勒综合征的婴儿，以及目前的干细胞移植如何导致 疾病相关的发病率和死亡率。提出的每个目标都将在彼此的背景下进行评估，以 提供详细的、多维的数据，旨在定义系统负担，作为未来治疗的衡量标准。

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.