Natural History Project

自然历史项目

• 批准号: 10686330
• 负责人: Christina Lam
• 金额: $ 32.45万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10686330
• 关键词: Affect; Biochemical; Blood; Caring; Cells; Characteristics; Childhood; Clinical; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Collection; Congenital disorders of glycosylation; Consensus; Control Groups; Data; Data Set; Defect; Development; Diagnostic; Disease; Enrollment; Evaluation; Family; Functional disorder; Future; Gene Mutation; Genomics; Geography; Growth; Guidelines; Individual; Information Networks; Intervention; Knowledge; Laboratories; Link; Longterm Follow-up; Measures; Medical; Medical Records; Metabolic Diseases; Methods; Morbidity - disease rate; Natural History; Nature; Outcome Measure; Participant; Pathology; Patient Outcomes Assessments; Patients; Phase; Physicians; Prevalence; Protocols documentation; Quality of life; Questionnaires; Recommendation; Recording of previous events; Research; Research Personnel; Route; Sampling; Selection Bias; Severities; Site; Surveys; Symptoms; System; Testing; Therapeutic; Therapeutic Trials; Travel; Update; Urine; Visit; biobank; biomarker discovery; body system; clinical care; clinical trial readiness; clinically relevant; cognitive disability; cognitive function; cohort; data de-identification; design; efficacy evaluation; empowerment; follow-up; frontier; glycosylation; improved; interest; medical specialties; medically underserved; mortality; multidisciplinary; pre-clinical; prospective; shared database; symptom management; targeted treatment; therapeutic development; treatment trial; virtual; web site

NATURAL HISTORY PROJECT-ABSTRACT/PROJECT SUMMARY Congenital disorders of glycosylation (CDG), a rapidly growing group of metabolic diseases characterized by an abnormal glycosylation of biomolecules, were first described in 1980, but the first gene mutation underlying CDG was only found in 1997. Exomic and genomic sequencing engendered a rapid discovery phase of more than 130 different CDG types. Clinical manifestations are variable within and among different types, so physicians from every specialty will likely encounter patients affected by glycosylation defects. Still, limited natural history information is available for the majority of CDG due to their novelty and individual rarity. Existing studies, mostly retrospective, are subject to selection bias, missing data-points and validated patient-reported outcomes. These factors result in knowledge gaps and clinical challenges in CDG treatments and clinical trial readiness. This project's purpose is to perform a multidisciplinary long-term follow-up of a large group of individuals with CDG to define natural history, validate patient reported outcomes and share knowledge on CDG. Our clinical study team has functioned as a virtual expert consortium and will further collaborate by collecting longitudinal data to assess biochemical characteristics, growth, cognitive function, organ system involvement, medical management of symptoms, and patient reported outcomes, as well as morbidity and mortality of individuals with CDGs. To fill in our knowledge gaps in CDG, we will 1) establish the prevalence and severity of specific morbid indicators such as organ system involvement, degree of cognitive disability, and case-fatality associated with various CDG and to establish a dynamic platform to effectively disperse clinically relevant findings to families, non-expert clinicians and researchers, as well as providing a verified method to link these individuals to experts in CDG; and 2) validate the CDG rating scale and patient reported outcome /quality of life measures for CDG. During the follow up we will collect and share samples for biomarker discovery and for bio-banking. The impact of this study will be our increased understanding of CDG and improved care of affected individuals. Natural history and progression studies will further elucidate the pathophysiology of disease and will be essential for clinical trial readiness. Sharing samples and bio-banking will significantly improve diagnostics. Establishing clinical trial outcome measures is essential for successful therapeutic development. This study will additionally enable families and clinicians to access accurate current information empowering them to seek appropriate intervention.

自然历史项目-摘要/项目总结 先天性糖基化障碍（CDG）是一组快速增长的代谢性疾病，其特征是 1980年首次描述了生物分子的异常糖基化，但第一个导致CDG的基因突变 直到1997年才被发现外显子组和基因组测序产生了一个快速发现阶段， 不同的CDG类型。临床表现是可变的内部和不同类型之间，所以医生从每一个 专科可能会遇到受糖基化缺陷影响的患者。尽管如此，有限的自然历史信息 由于其新奇和个别稀有性，可供大多数CDG使用。现有的研究，大多是回顾性的， 受选择偏倚、缺失数据点和经验证的患者报告结局的影响。这些因素导致 CDG治疗和临床试验准备方面的知识差距和临床挑战。该项目的目的是 对一大群CDG患者进行多学科长期随访，以确定自然史， 验证患者报告的结果并分享有关CDG的知识。 我们的临床研究团队作为一个虚拟专家联盟，将通过收集 纵向数据，以评估生化特征、生长、认知功能、器官系统受累， 症状的医学管理，患者报告的结局，以及个体的发病率和死亡率 关于CDG 为了填补我们在CDG方面的知识空白，我们将1）建立特定疾病指标的患病率和严重程度 如器官系统受累、认知障碍程度以及与各种CDG相关的病死率 并建立一个动态平台，有效地将临床相关发现分散到家庭，非专家， 临床医生和研究人员，以及提供一种经过验证的方法，将这些人与CDG专家联系起来;以及2） 验证CDG评定量表和患者报告的CDG结局/生活质量指标。在随访 我们将收集和分享用于生物标志物发现和生物银行的样本。 这项研究的影响将是我们对CDG的了解增加，并改善对受影响个体的护理。 自然史和进展研究将进一步阐明疾病的病理生理学， 临床试验准备。共享样本和生物库将大大改善诊断。建立临床 试验结果测量对于成功的治疗开发是必不可少的。这项研究还将使 家庭和临床医生可以获取准确的当前信息，使他们能够寻求适当的干预措施。