Multiplex Analysis of Inborn Errors of Metabolism

描述(由申请人提供)： 拟议研究的统一目标是开发具有诊断价值的酶活性的多重分析的分析方法，以检测先天性代谢错误。这些检测是以串联质谱仪作为通用分析平台对酶产物进行定量分析的基础上的。在前三年的资助期内，我们利用新生儿筛查卡上的干血斑点，开发了几种溶酶体储存疾病的串联质谱学分析方法。我们还开发了用于临床检测三种卟啉症的质谱分析方法。我们对溶酶体储存疾病的串联质谱分析的研究已经对医学界产生了重大影响，我们开发的一些分析已经从我们的实验室过渡到美国和世界各地的几个新生儿筛查实验室。这项拟议的研究旨在利用新生儿筛查卡上的干血点来检测Hunter、Maroteaux-Lamy、Morquio A、异色素性脑白质营养不良和Sanfilippo A-D综合征。这些溶酶体储存障碍的治疗方法已经可用或正在开发中，我们的检测将使新生儿筛查实验室有可能在出现不可逆转症状之前检测到这些疾病。还建议继续研究与卟啉相关的酶氨基乙酰丙酸脱水酶、胆红素原氧化酶和铁络合酶，以建立一套完整的基于串联质谱学的卟啉分析方法。 公共卫生相关性： 这项研究的目的是开发基于酶分析和串联质谱仪产品分析的选择性和灵敏方法。为了继续我们以前在这一领域的成功努力，提出了几种溶酶体储存疾病的早期检测技术和程序。

DESCRIPTION (provided by applicant): The unifying goal of the proposed studies is the development of assays for the multiplex analysis of enzyme activities of diagnostic value for the detection of inborn errors of metabolism. The assays are based on quantitative analysis of enzymatic products by tandem mass spectrometry as a common analytical platform. In the previous 3-year funding period we have developed tandem mass spectrometric assays for several lysosomal storage diseases using dried blood spots on newborn screening cards. We have also developed mass spectrometric assays for the clinical detection of three porphyrias. Our research on tandem mass spectrometric assays of lysosomal storage diseases has already had a significant impact on the medical community, and some of the assays we developed have been transitioned from our lab to several newborn screening labs in the U.S. and worldwide. The proposed research aims at the detection of syndromes of Hunter, Maroteaux-Lamy, Morquio A, Metachromatic Leukodystrophy, and Sanfilippo A-D using dried blood spots on newborn screening cards. Treatments for these lysosomal storage disorders are either available or being developed and our assays will make it possible for newborn screening laboratories to detect these diseases prior to the development of irreversible symptoms. Also proposed is a continuation of studies of porphyria-linked enzymes aminolevulinic acid dehydratase, porphobilinogen oxidase, and ferrochelatase to develop a complete battery of assays for porphyrias based on tandem mass spectrometry. PUBLIC HEALTH RELEVANCE: The proposed research is aimed at the development of selective and sensitive methods based on enzyme assays and product analysis by tandem mass spectrometry. Technologies and procedures for the early detection of several lysosomal storage diseases are proposed in continuation of our previous successful efforts in this area.