Implementing Newborn Screening for Duchenne Muscular Dystrophy in the Community

摘要 在与疾病预防控制中心的合作协议中，新生儿筛查计划（NBS）的关键基础是 建立杜氏肌营养不良症（DMD），包括：肌酸激酶（CK）范围 在> 30，000个匿名样本上观察到，这是一种测量CK同工酶的成功方法， 重点是CK-MB，以及抗肌萎缩蛋白基因DNA分析的可靠方法， 已知的DMD突变这些实验室方法使我们能够对DMD进行从最初的干燥 出生时采集的血斑样本，以后没有采集额外的血液。这些成就 使得有可能提出一个更广泛的计划，以涵盖大多数分娩医院在 俄亥俄州，履行翻译一个实验室为基础的计划，以社区的真正精神。引人注目 使这成为现实的原因包括：1）DMD是最常见的破坏性肌肉疾病， 2）NBS将对疾病和社区产生重大影响，提供早期干预， 治疗（包括皮质类固醇的使用和激动人心的分子和药理学方法综述 3）许多家庭面临的后期诊断挑战的过度费用和焦虑; 4） 为有更多儿子患DMD风险的家庭提供遗传咨询（多个男孩患DMD导致 巨大的经济开支，充满内疚的父母，以及离婚率的上升）。 在这项提案中，NBS将扩展到整个俄亥俄州，覆盖75,000名新生男性。的 第一年将集中在组织，并将允许我们：1）建立一个行政核心，以管理 参与医院网络（AIM 1）; 2）建立一个实验室核心，用于评估CK和DNA， 抗肌萎缩蛋白基因（AIM 2）; 3）建立参与该计划的医院网络（AIM 3）。开始 在第一年，并继续在第二年和第三年将实施75,000名男性DMD的NBS （目标4）。该计划的成功将为将DMD的NBS扩展到其他州提供一个模板， 使之成为一个全国性的自愿筛查项目的潜力。这样的计划将使一个差异， 这种疾病。项目叙述 杜氏肌营养不良症（DMD）是儿童期最常见的破坏性肌肉疾病。家庭 经常负担着多个受影响的男孩，因为第一个男孩通常直到5岁才被诊断出来， 家庭的巨大开支和困难。早期治疗可以为DMD男孩带来不同， 更好的治疗方法即将出现。这项提案将在俄亥俄州建立一个全州范围的新生儿计划， 筛查DMD，可以作为一个模板，将其扩展到国家自愿筛查计划。

ABSTRACT In a cooperative agreement with the CDC, the critical groundwork for a newborn screening program (NBS) for Duchenne muscular dystrophy (DMD) was established and included: the range of creatine kinase (CK) observed on > 30,000 anonymous samples, a successful method to measure CK isoenzymes, with particular emphasis on CK-MB, and a reliable method of DNA analysis of the dystrophin gene, with validation from known DMD mutations. These laboratory approaches permit us to do all NBS for DMD from the initial dried blood spot samples taken at birth without obtaining additional blood at a later time. These achievements have made it possible to propose a more extended program to cover the majority of the birthing hospitals in the State of Ohio, fulfilling the true spirit of translating a laboratory-based program to the community. Compelling reasons for making this a reality include: 1) DMD is the most common devastating muscle disease of childhood; 2) NBS will have a major impact on the disease and community offering early intervention and treatment (including the use of corticosteroids and exciting molecular and pharmacologic approaches reviewed in this proposal); 3) excessive expense and anxiety of the later diagnostic challenge faced by many families; 4) genetic counseling to families at risk for having more sons with DMD (multiple boys with DMD leads to overwhelming financial expenses, guilt-laden parents, and increased incidence of divorce). In this proposal, NBS will be extended throughout the State of Ohio, reaching 75,000 newborn males. The first year will be focused on organization and will permit us to: 1) establish an Administrative Core to manage a network of participating hospitals (AIM1); 2) establish a Laboratory Core for evaluation of CK and DNA for the dystrophin gene (AIM2); and 3) establish the network of hospitals participating in this program (AIM3). Starting in year 1 and continuing in years 2 and 3 will be the implementation of the NBS of 75,000 males for DMD (AIM4). The success of this program will provide a template for expanding NBS for DMD to other States with the potential of making this a national voluntary screening program. Such a program will make a difference for this disease. PROJECT NARRATIVE Duchenne muscular dystrophy (DMD) is the most common devastating muscle disease of childhood. Families are often burdened with multiple affected boys because the first is not often diagnosed until age 5, resulting in overwhelming expense and hardship for families. Early treatment can make a difference for DMD boys and better treatments are on the horizon. This proposal will establish a statewide program in Ohio for newborn screening for DMD that can be used as a template to expand this to a national voluntary screening program.