Implementing Newborn Screening for Duchenne Muscular Dystrophy in the Community

描述(由申请人提供)：在与疾控中心的一项合作协议中，为杜氏肌营养不良(DMD)新生儿筛查计划(NBS)建立了关键的基础工作，其中包括：在30,000个匿名样本上观察到的肌酸激酶(CK)的范围，一种成功地测量CK同工酶的方法，尤其是CK-MB，以及一种可靠的dystrophin基因的DNA分析方法，该方法通过已知的DMD突变进行验证。这些实验室方法允许我们从出生时采集的初始干血斑样本中进行所有DMD的NBS检查，而不需要在以后获取额外的血液。这些成就使得提出一个更广泛的计划来覆盖俄亥俄州的大多数分娩医院成为可能，实现了将以实验室为基础的计划转化为社区的真正精神。使这成为现实的令人信服的理由包括：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(包括使用皮质类固醇和本申请中综述的令人兴奋的分子和药理学方法)；3)许多家庭后来面临的诊断挑战的过度费用和焦虑；4)为有风险生更多患有DMD的儿子的家庭提供遗传咨询(多个患有DMD的男孩导致巨大的经济支出，负罪感的父母，并增加离婚率)。在这项申请中，国家统计局将扩展到整个俄亥俄州，覆盖7.5万名新生男性。第一年将重点放在组织上，并将允许我们：1)建立行政核心来管理参与计划的医院网络(AIM1)；2)建立评估肌营养不良蛋白基因CK和DNA的实验室核心(AIM2)；以及3)建立参与该计划的医院网络(AIM3)。从第一年开始，在第二年和第三年继续执行国家统计局对75,000名男性的DMD(AIM4)。这项计划的成功将为将DMD的国家统计局扩大到其他州提供模板，并有可能使其成为国家自愿筛查计划。这样的计划将对这种疾病产生不同的影响。

DESCRIPTION (provided by the applicant): 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 application); 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 application, 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.