Multiplex Analysis of Inborn Errors of Metabolism

先天性代谢缺陷的多重分析

• 批准号: 7426533
• 负责人: FRANTISEK TURECEK
• 金额: $ 7.49万
• 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/7426533
• 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; Mucopolysaccharidosis VI; 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

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), MPS- VI (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 otherLSD. 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.

我们提出的研究的统一目标是进一步发展串联质谱法（MS）， 用于检测具有诊断价值的酶活性的多重分析方法 先天性代谢缺陷串联MS分析将开发用于与以下相关的酶： 属于粘多糖沉积病II组（MPS-II，Hunter）的溶酶体贮积病（LSD）， VI（Maroteaux-Lamy）和异染性脑白质营养不良，在新生儿筛查中使用干血斑 卡作为酶源。这些疾病的治疗正处于后期开发阶段，我们的试验将 使新生儿筛查实验室能够在这些疾病发展之前发现这些疾病， 不可逆的表型异常 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）。 Sanfilippo综合征的生化分析是困难的，因为相同的表型症状 当四种不同的酶之一缺乏时，患者会出现这种情况。此外，以前的试验， 由于需要使用不同测定技术的集合，因此相关酶的测定是困难的。 与Sanfilippo综合征相关的所有四种酶的串联MS测定将使用相同的单一分析方法 平台上的其他LSD。 我们将开发血红素生物合成途径中的酶的测定方法，以用于 各种形式的卟啉症卟啉通常不在大多数临床实验室中测定，因为 需要高度专业化的协议。我们将尝试开发串联MS检测所有的个人 血红素生物合成途径中的酶，使得该测定可以在大量的 实验室，这将有助于医生诊断这一系列疾病。