Collaborative Defining the Natural History of Inborn errors of Metabolism

描述（由申请人提供）：新生儿血斑筛查的主要假设是，早期诊断和治疗是一个很好的公共资源投资，无论是对个人和社会的测试。 虽然改善结果的一些效果似乎是不言而喻的，但对于大多数新筛查的疾病，没有对筛查确定的儿童的结果进行全面，长期的评估。 为了验证早期识别，干预和治疗的有效性，纵向评估结果是必不可少的。 更好地了解罕见代谢紊乱的自然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。 由来自10个州的13个诊所组成的先天性代谢缺陷协作组织（IBEMC）将收集纵向数据，这些数据将捕捉受新生儿筛查确定的疾病影响的人的临床进展，重点是先天性代谢缺陷。 数据将用于更好地定义自然史并了解治疗干预的效果。 数据库将允许：1.探讨NBS值、基因型与先天性代谢缺陷的早期表现及并发症的关系。评估早期识别和干预对代谢状况的影响; 3.国家统计局公共卫生最优投资的知情决策;澄清以前未定义的非常罕见的代谢疾病的自然史;和5。确定目前对代谢性疾病儿童的营养和治疗干预措施，并评估其有效性。 IBEMC将以HRSA资助的第4区遗传学合作组织的工作为基础，并与新生儿筛查转化研究网络等其他国家工作合作开发。 该项目将建立创新实践，使临床医生参与合作文化，提供激励措施，以确保收集摄入量和间隔数据，并提供支持，鼓励数据分析。 这些努力将导致研究，为临床试验设计和改善先天性代谢缺陷儿童的治疗提供基础。 相关性：由于有足够数量的罕见疾病病例被录入，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，早期诊断和治疗是对公共资源的良好投资，无论是对个人还是对社会，NBS公共卫生范式可能会改变。 这是可能的，在IBEM的自然历史的知识的增加将导致如何添加到NBS面板的条件的变化，并在面板目前的条件可能会被审查和修订。

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.