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)的关键基础工作是 建立Duchenne型肌营养不良症(DMD)模型，包括：肌酸激酶(CK)的范围 在3万份匿名标本上观察到的CK同工酶测定方法，具有较强的特异性。 强调CK-MB，以及一种可靠的Dstrophin基因DNA分析方法，验证来自 已知的DMD突变。这些实验室方法允许我们从最初干燥的DMD进行所有的NBS 在出生时采集血斑样本，而不在以后获取额外的血液。这些成就有 有可能提出一项更广泛的计划，覆盖世界上大多数的分娩医院 实现了将以实验室为基础的项目转化为社区的真正精神。引人入胜 实现这一目标的原因包括：1)DMD是最常见的破坏性肌肉疾病 2)国家统计局将对疾病和社区产生重大影响，提供早期干预和 治疗(包括皮质类固醇的使用以及令人兴奋的分子和药理学方法综述 在本提案中)；3)过高的费用和许多家庭面临的后期诊断挑战的焦虑；4) 为有可能生更多患有DMD的儿子的家庭提供遗传咨询(多个患有DMD的男孩会导致 不堪重负的经济支出，充满负罪感的父母，以及离婚率上升)。 在这项提案中，NBS将扩展到整个俄亥俄州，覆盖7.5万名新生男性。这个 第一年将重点放在组织上，使我们能够：1)建立管理核心来管理 参与医院网络(AIM1)；2)建立用于评估CK和DNA的实验室核心 Dystrophin基因(AIM2)；以及3)建立参与该计划的医院网络(AIM3)。启动 在第一年和第二年和第三年将实施75,000名男性DMD的国家统计局 (AIM4)。该计划的成功将为将DMD的国家统计局扩展到其他国家提供模板 使这一计划成为国家自愿筛查计划的潜力。这样的计划将对 这种病。项目叙事 Duchenne肌营养不良症(DMD)是儿童最常见的破坏性肌肉疾病。家庭 经常有多个受影响的男孩，因为第一个男孩通常直到5岁才被诊断出来，导致 家庭的巨大开支和困难。早期治疗可以改变DMD男孩和 更好的治疗方法即将出现。这项提案将在俄亥俄州为新生儿建立一个全州范围的计划 可以作为模板的DMD筛查，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.