Longitudinal Studies of Brain Structure and Function in MPS Disorder

粘多糖症是一种溶酶体疾病，通常从童年开始就会逐渐影响到身体的大多数器官系统。最近的治疗进展已经改善了其中一些功能障碍，但特别是大脑和骨骼一直很难治疗。这项研究针对的是 MPS障碍中的大脑异常，目前知之甚少。 这项研究的目标是： 1)明确中枢神经系统(CNS)结构和功能的异常，并测量治疗和未治疗的MPS患者随时间的生活质量(QOL)。我们将通过对北美核心中心登记的患者进行纵向研究来实现这一点，这些中心构成了溶酶体疾病网络(LDN)。我们假设对于每一种MPS障碍，特定的和局部的神经影像和神经心理学的发现及其关系将是不同的。此外，如果不进行治疗，功能将下降，结构将以可预见的方式随着时间的推移而变化，并将与异常部位和疾病阶段有关 2)发展变化的定量测量；包括直接测量神经心理功能，替代MRI标志物，以及用于衡量疾病阶段和治疗结果的生物标志物。 3)检查自变量(如首次治疗的年龄、疾病的严重程度、医学异常的类型、突变、医疗事件、感觉异常等)对大脑功能和结构变量以及生活质量的影响程度。 4)探讨ERT、HSCT、底物减少术及其他姑息和康复治疗对中枢神经系统结构和功能及生活质量的影响。 方法：在最初的两年中，来自8个中心的70名儿童将在5年内被纳入本研究，其中MPS I组30名，MPS II组20名，MPS VI组20名。每名儿童每年至少进行3次或可能4次随访。定量神经影像与神经心理学 将使用议定书收集数据以及可能影响这些措施的相关医疗和环境变量。还将收集一种可能对变化敏感的新生物标记物。将对数据进行分析，以确定中枢神经系统异常的位置、对变化和疾病进展的措施的敏感性，并确定影响这些结果的变量。

The mucopolysaccharidoses are lysosomal disorders that progressively affect most organ systems in the body usually beginning in childhood. Recent treatment advances have produced amelioration of some of these malfunctions, but notably brain and bone have been difficult to treat. This research addresses the brain abnormalities in the MPS disorders about which little is known. The objectives of this research are: 1) to identify abnormalities of central nervous system (CNS) structure and function as well as to measure quality-of-life (QOL) in both treated and untreated patients with MPS disorders over time. We will accomplish this through longitudinal studies of enrolled patients in core centers in North America that constitute the Lysosomal Disease Network (LDN). We hypothesize that specific and localized neuroimaging and neuropsychological findings and their relationship will be distinct for each MPS disorder. Further, without treatment, functions will decline and structure will change over time in a predictable fashion, and will be related to locus of abnormality and stage of disease 2) to develop quantitative measurements of change; including direct measurement of neuropsychological function, surrogate MRI markers, and biomarkers to measure stage of disease and treatment outcomes. 3) to examine the degree to which independent variables ( such as age at first treatment, severity of disease, types of medical abnormalities, mutation, medical events, sensory abnormalities and others) have an impact on both functional and structural outcome brain variables as well as quality-of-life. 4) to examine how treatments such as ERT, HSCT, substrate reduction and other palliative and rehabilitation therapies differentially affect CNS structure and functions and quality of life (QOL). Methods: Over the first two years 70 children will be enrolled and followed in this study from 8 centers over five years; 30 MPS I, 20 MPS II, and 20 MPS VI. Each child will be seen yearly for a total of at least 3 or possibly 4 follow-up visits within the five year period. A quantitative neuroimaging and neuropsychological protocol will be used to collect data as well as relevant medical and environmental variables that may impact these measures. A new biomarker that may be sensitive to change will also be collected. Data will be analyzed to determine the locus of central nervous system abnormality, the sensitivity of measures to change and disease progression, and to identify the variables that contribute to these outcomes.