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用于检测先天性代谢缺陷的诊断价值的酶活性的多重分析的测定法。该测定基于通过串联质谱法作为通用分析平台对酶产物进行的定量分析。在过去的3年资助期内，我们已经开发了串联质谱分析，用于使用新生儿筛查卡上的干血斑检测几种溶酶体贮积病。我们还开发了三种卟啉症的临床检测质谱分析。我们对溶酶体贮积病的串联质谱检测的研究已经对医学界产生了重大影响，我们开发的一些检测方法已经从我们的实验室转移到美国和世界各地的几个新生儿筛查实验室。拟议的研究旨在使用新生儿筛查卡上的干血斑检测Hunter、Maroteaux-Lamy、Morquio A、异染性脑白质营养不良和Sanfilippo A-D综合征。这些溶酶体贮积症的治疗方法要么是可用的，要么正在开发中，我们的检测将使新生儿筛查实验室有可能在不可逆症状出现之前检测到这些疾病。还提议继续研究与卟啉症相关的酶--氨基酮戊酸脱水酶、胆色素原氧化酶和铁螯合酶，以开发一套完整的基于串联质谱的卟啉症检测方法。 公共卫生相关性： 拟议的研究旨在开发基于酶测定和串联质谱产品分析的选择性和灵敏度方法。技术和程序的早期检测几种溶酶体贮积病的建议，继续我们以前在这方面的成功努力。

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.