ASYMPTOMATIC METACHROMATIC LEUKODYSTROPHY SCREENING

注定要死于异色性的无症状婴儿 脑白质营养不良症(MLD)，可以通过尿中硫脂阳性来确定。 当在生命早期被发现时，骨髓移植可以提供， 根据最初的数据，这是一种有效的、或许是治愈的治疗方法。 MLD患者的尿硫脂升高是其特征 疾病。硫脂的检测可以通过尿液浸泡来完成 滤纸，一种用于大规模筛选其他 疾病。滤纸中的硫脂可以被提取并通过 电喷雾电离质谱仪。这一二期工程将：1. 进行半自动尿硫脂和鞘磷脂分析 通过电喷雾收集10,000张之前浸泡过尿液的滤纸 电离质谱仪以a)建立和验证稳健的 异色性脑白质营养不良筛查程序和b)估计错误 阳性频率，以及2.识别MLD尿液和MLD的发生 可能的假阴性频率，并演示商业 MLD半自动筛查方法的适用性研究 尿硫脂和鞘磷脂分析-10万以前 收集浸泡尿液的滤纸，3.通过以下方式提高方法效率 测试技术和设计方面的新进步。 建议的商业应用： 一种筛查6月龄婴儿异染性脑白质营养不良的方法 将会被开发出来。在持续证明以下事项的有效性之后 骨髓中的筛选方法和阳性强化 移植后，接受筛查的婴儿数量可能会 每年有几百万人。这项研究的商业应用 将通过许可、合资或测试实现 加上成本和利润。

Asymptomatic infants who are destined to die from metachromatic leukodystrophy (MLD), can be identified by urine positive for sulfatides. When detected early in life, bone marrow transplantation can provide, according to initial data, an effective, perhaps curative, treatment. Elevated urine sulfatides of MLD patients are characteristic of this disease. Detection of sulfatides can be accomplished by using urine-soaked filter paper, a collection method used for mass screening of other diseases. Sulfatides from filter papers can be extracted and quantified by electrospray ionization mass spectrometry. This Phase II project will: 1. perform semi-automated urinary sulfatide and sphingomyelin analysis of 10,000 previously collected urine-soaked filter papers by electrospray ionization mass spectrometry to a) establish and validate a robust procedure for metachromatic leukodystrophy screening and b) estimate false positive frequency, and to 2. identify MLD urines and the occurrence of possible false negative frequency, and to demonstrate the commercial applicability of the method of MLD screening by performing semi-automated urinary sulfatide and sphingomyelin analysis of - 100,000 previously collected urine-soaked filter paper, 3. improve on method efficiency by testing new advancements in technology and design. PROPOSED COMMERCIAL APPLICATION: A method of screening 6-month-old infants for metachromatic leukodystrophy will be developed. Subsequent to continued proof of validity of the screening method and positive reinforcement from bone marrow transplantation, the number of infants screened will potentially be several million each year. The commercial application of this research will then be realized from either licensing, joint venture, or testing with cost plus profit.