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法（MS）作为一种分析方法，用于用于诊断价值的酶活性的多重分析，以检测代谢的先天错误。串联MS分析将用于与粘多糖体疾病（LSD）有关的酶II（MPS-II，Hunter），MPSVI（Maroteaux-Lamy）和使用新生的eNBENT sprecyme的酶。这些疾病的治疗是在晚期发育中，我们的测定方法将使新生儿筛查实验室在发展不可逆的表型异常之前发现这些疾病。另一组要解决的疾病是Sanfilippo综合征A-D（粘多糖酸IIIA-D）。 Sanfilippo综合征的生化分析很困难，因为当四种不同的酶之一缺乏时，患者中存在相同的表型症状。此外，由于需要使用不同的测定技术的集合，因此相关酶的先前测定很困难。与Sanfilippo综合征相关的所有四种酶的串联MS分析将使用与其他LSD相同的单个分析平台。我们将在血红素生物合成途径中开发酶的测定法，以对各种形式的卟啉症进行生化诊断。由于需要高度专业的方案，因此在大多数临床实验室中通常不会在大多数临床实验室中进行测定。我们将尝试为血红素生物合成途径中所有单个酶开发串联MS分析，以便可以在大量的实验室中进行测定，这将帮助医生诊断这套疾病。