Collaborative Defining the Natural History of Inborn errors of Metabolism

描述(由申请人提供)：新生儿血斑筛查的基本假设是，早期诊断和治疗是对公共资源的良好投资，无论是对检测的个人还是对社会都是如此。尽管改善结果的一些效果似乎不言而喻，但对于大多数新生儿筛查疾病来说，对筛查确定的儿童的结果没有全面的、长期的评估。为了验证早期识别、干预和治疗的有效性，对结果的纵向评估是必不可少的。更好地了解罕见代谢紊乱的自然病史和当前治疗的有效性，对于为患有这些疾病的儿童提供最佳护理和促进最佳结果是必要的。 先天代谢错误合作(IBEMC)由来自10个州的13个诊所组成，将收集纵向数据，捕捉受新生儿筛查确定的疾病影响的人的临床进展，重点是先天代谢错误。数据将被用来更好地定义自然病史和了解治疗干预的效果。该数据库将允许：1.调查NBS值、基因型和早期表现之间的关系以及先天代谢错误的并发症；2.评估早期识别和干预对代谢状况的影响；3.关于国家统计局最佳公共卫生投资的知情决策；4.澄清以前未定义的非常罕见的代谢状况的自然历史；以及5.确定当前对有代谢状况的儿童的营养和治疗干预并评估其有效性。 IBEMC将以人权事务管理局资助的第4区遗传学合作项目的工作为基础，并与包括新生儿筛查转化研究网络在内的其他国家的努力合作发展。该项目将建立创新的做法，让临床医生参与到协作文化中来，提供激励措施以确保收集摄入量和间隔数据，并提供支持以鼓励数据分析。这些努力将导致研究结果，为临床试验设计和改善对患有先天性新陈代谢疾病的儿童的治疗提供基础。 相关性：随着更罕见的疾病进入足够数量的病例，研究将为早期诊断和治疗的有效性提供证据。如果研究不支持国家统计局所依据的假设，即早期诊断和治疗对接受测试的个人和社会来说都是对公共资源的良好投资，国家统计局的公共卫生范式可能会改变。关于IBEM自然历史的知识的增加可能会导致国家统计局小组增加条件的方式发生变化，目前小组中的条件可能会得到审查和修订。

DESCRIPTION (Provided by Applicant): Newborn blood spot screening is undertaken with the primary assumption that early diagnosis and treatment is a good investment of public resources, both for the individuals tested and for society. Although some effects of improved outcomes seem self-evident, for most newborn-screened disorders there is no comprehensive, long-term assessment of outcomes for children identified by screening. To verify the effectiveness of early identification, intervention, and treatment, longitudinal assessment of outcomes is essential. A better understanding of the natural histories of rare metabolic disorders and the effectiveness of current treatments is necessary to provide optimum care and promote the best possible outcomes for children with these conditions. The Inborn Errors of Metabolism Collaborative (IBEMC), consisting of 13 clinics from 10 states, will collect longitudinal data that capture the clinical progress of persons affected with conditions identified by newborn screening, focusing on inborn errors of metabolism. Data will be used to better define the natural histories and understand the effect of treatment interventions. The database will allow for: 1. Investigation of the relationship among NBS values, genotype, and early manifestations as well as complications of inborn errors of metabolism; 2. Evaluation of the impact of early identification and intervention on metabolic conditions; 3. Informed decision making about optimal public health investment in NBS; 4. Clarification of the previously undefined natural history of very rare metabolic conditions; and 5. Identification of current nutritional and therapeutic interventions for children with metabolic conditions and evaluation of their effectiveness. The IBEMC will build on the work of the HRSA-funded Region 4 Genetics Collaborative and be developed in collaboration with other national efforts, including the Newborn Screening Translational Research Network. The project will establish innovative practices to engage clinicians in a culture of collaboration, provide incentives to ensure collection of both intake and interval data, as well as offer supports that encourage data analysis. These efforts will result in investigations that provide a foundation for clinical trial design and improved treatment for children with inborn errors of metabolism. RELEVANCE: As a sufficient number of cases are entered for the rarer disorders, research will provide evidence as to the efficacy of early diagnosis and treatment. If research does not support the assumption on which NBS is based, i.e., early diagnosis and treatment are good investments of public resources, both for the individuals tested and for society, the NBS public health paradigm may change. It is possible that the increase in knowledge about the natural history of IBEM will lead to a change in how conditions are added to the NBS panel and that the conditions currently in the panel may be reviewed and revised.