Multiplex Analysis of Inborn Errors of Metabolism

先天性代谢缺陷的多重分析

• 批准号: 7265273
• 负责人: FRANTISEK TURECEK
• 金额: $ 29.38万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7265273
• 关键词: Amino Acids; Biochemical; Biochemical Pathway; Biological Assay; Blood; Carnitine; Clinical; Collection; Detection; Development; Diagnosis; Diagnostic; Disease; Enzymes; Goals; Heme; Inborn Errors of Metabolism; Individual; Infusion procedures; Laboratories; Lysosomal Storage Diseases; Metachromatic Leukodystrophy; Mucopolysaccharidoses; Mucopolysaccharidosis II; Mucopolysaccharidosis III; Neonatal Screening; Numbers; Pathway interactions; Patients; Physicians; Porphyrias; Protocols documentation; Source; Spottings; Staging; Symptoms; Syndrome; Techniques; analytical method; enzyme activity; mass spectrometer; organic acid; tandem mass spectrometry

DESCRIPTION (provided by applicant): The unifying goal of our proposed studies is to further develop tandem mass spectrometry (MS) as an analytical method for the multiplex analysis of enzyme activities of diagnostic value for the detection of inborn errors of metabolism. Tandem MS assays will be developed for the enzymes relevant to the lysosomal storage diseases (LSD) belonging to the Mucopolysaccharidosis groups II (MPS-II, Hunter), MPSVI (Maroteaux-Lamy), and metachromatic leukodystrophy, using dried blood spots on newborn screening cards as the enzyme source. Treatment of these disorders is in late-stage development, and our assays will make it possible for newborn screening laboratories to spot these diseases prior to the development of irreversible phenotypic abnormalities. Another group of diseases to be tackled is the Sanfilippo syndromes A-D (Mucopolysaccharidosis IIIA-D). The biochemical analysis of Sanfilippo syndromes is difficult because the same phenotypic symptoms present in patients when one of the four different enzymes is deficient. Furthermore, previous assays of the relevant enzymes have been difficult owing to the need to use a collection of different assay techniques. Tandem MS assays of all four enzymes relevant to Sanfilippo syndrome will use the same single analytical platform as for the other LSD. We will develop assays for enzymes in the heme biosynthetic pathway for the biochemical diagnosis of the various forms of porphyrias. Porphyrias are not typically assayed in most clinical laboratories because of the need for highly specialized protocols. We will attempt to develop tandem MS assays for all of the individual enzymes in the heme biosynthetic pathway so that the assay can be carried out in a larger number of laboratories, which will help physicians diagnose this set of disorders.

描述（由申请人提供）： 我们提出的研究的统一目标是进一步开发串联质谱（MS）作为一种分析方法，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。将使用新生儿筛查卡上的干血斑作为酶源，开发与属于粘多糖贮积病II组（MPS-II，Hunter）、MPSVI（Maroteaux-Lamy）和异染性脑白质营养不良的溶酶体贮积病（LSD）相关的酶的串联MS测定法。这些疾病的治疗处于后期发展阶段，我们的检测将使新生儿筛查实验室能够在不可逆表型异常发展之前发现这些疾病。另一组需要解决的疾病是Sanfilippo综合征A-D（粘多糖沉积症IIIA-D）。圣菲利波综合征的生化分析是困难的，因为当四种不同的酶之一缺乏时，患者会出现相同的表型症状。此外，由于需要使用一系列不同的检测技术，之前对相关酶的检测一直很困难。与Sanfilippo综合征相关的所有四种酶的串联MS测定将使用与其他LSD相同的单一分析平台。我们将开发血红素生物合成途径中的酶的检测方法，用于各种形式卟啉症的生化诊断。由于需要高度专业化的方案，大多数临床实验室通常不对卟啉病进行检测。我们将尝试为血红素生物合成途径中的所有单个酶开发串联MS测定，以便可以在更多的实验室中进行测定，这将有助于医生诊断这组疾病。