LSDs:A Pilot NBS and Examination of the Associated Ethical Legal & Social Issues

描述（由申请人提供）： 包括纽约在内的几个州已提出对新生儿进行法布里病、戈谢病、尼曼匹克病A型和B型以及庞贝氏症筛查。这些溶酶体贮积病（LSD）中的每一种都具有广泛的表型谱，范围从严重的战斗发病疾病到成人发病的较温和的表型。因此，新生儿筛查这些疾病提出了一套独特的复杂的问题，需要调查之前启动大规模新生儿筛查。这些问题包括确定筛查检测的临床和诊断准确性，研究如何正确预测无症状新生儿的表型，以及开发算法以帮助临床决策是否以及何时开始治疗。此外，有新的伦理，法律的，和社会问题与测试婴儿潜在的晚发型疾病。本提案将通过与纽约州新生儿筛查计划联合实施一项试点新生儿筛查来探讨这些问题，以评估筛查试验的分析和临床有效性，并确定不同种族人群的疾病发病率。筛查数据将与新生儿筛查转化研究网络（NBSTRN）共享。所有确定的婴儿将由西奈山医疗中心的LSD专家进行诊断评估，监测和治疗。从这项研究和现有的疾病特异性临床数据库中产生的自然史数据也将与NBSTRN共享，目的是开发模型来预测整个生命周期中疾病的发病年龄，以优化治疗并避免过早使用昂贵的治疗方法。还将探讨LSD筛查的心理学方面，重点是筛查迟发性疾病是否具有有害的短期或长期影响。心理影响将通过问卷调查和访谈进行评估，以评估其婴儿有发生婴儿期与晚发型疾病风险的父母的反应。我们还将通过分析监测和治疗费用以及保险的潜在困难，开始分析阳性诊断对家庭的经济影响。基于这些结果，将召集一个伦理委员会B，讨论与这些疾病检测相关的特殊问题，包括潜在危害，然后我们将使用这些信息作为制定政策建议的基础，对新生儿筛查LSD，特别是晚发型疾病。此外，还将举行一次专题讨论会，讨论参与成人发病患者新生儿筛查的医疗小组的法医学责任的范围和长度。总之，这些研究应导致发展循证，伦理敏感，新生儿筛查和长期随访政策，将有相当大的影响，新生儿筛查LSD成为广泛采用。

DESCRIPTION (provided by applicant): PROJECT SUMMARY Newborn screening for Fabry, Gaucher, Niemann Pick Types A and B, and Pompe diseases has been proposed in several states, including New York. Each of these lysosomal storage diseases (LSD) has a broad phenotypic spectrum ranging from severe infantile-onset disease to adult-onset, milder phenotypes. Thus, newborn screening for these disorders presents a unique set of complex issues that require investigation prior to the initiatio of mass newborn screening. These issues include determining the clinical and diagnostic accuracy of the screening assay, investigating how to correctly predict phenotype in asymptomatic newborns, and developing algorithms to assist with clinical decision-making about if and when to initiate therapy. In addition, there are novel ethical, legal, and social issus associated with testing infants for potentially later-onset disorders. This proposal will explore these issues by implementing a pilot newborn screen in conjunction with the New York State Newborn Screening Program to evaluate the analytic and clinical validity of the screening test and to determine disease incidence in an ethnically diverse population. Screening data will be shared with the Newborn Screening Translational Research Network (NBSTRN). All identified infants will be followed by LSD experts at The Mount Sinai Medical Center for diagnostic evaluation, monitoring, and treatment. Natural history data generated from this research and from existing disease-specific clinical databases will also be shared with the NBSTRN, with the goal of developing models to predict age of onset of disease over the lifespan in order to optimize treatment and avoid premature use of costly therapies. The psychological aspects of screening for the LSDs will also be explored, focusing on whether screening for later-onset disorders has harmful short or longer term effects. The psychological impact will be assessed using questionnaires and interviews to evaluate the reactions of parents whose infants are at risk to develop infantile versus later-onset disease. We will also initiate an analysis of the economic impact of a positive diagnosis on families by analyzing monitoring and treatment costs as well as potential difficulties with insurability. Based on these results, an ethics panel will b convened to discuss the particular concerns, including potential harms, that are associated with testing for these disorders, and we will then use this information as the basis for formulating policy recommendations on newborn screening for LSDs in general, and later onset diseases in particular. In addition, a symposium will be held to discuss the extent and length of medicolegal responsibility of the medical team involved in the newborn screening of a patient with adult onset disease. In sum, these studies should result in the development of evidence-based, ethically-sensitive, newborn screening and long-term follow up policies that will have considerable influence as newborn screening for the LSDs becomes widely adopted.