Rashed M S, Bucknall M P, Little D, Awad A, Jacob M, Alamoudi M, Alwattar M, Ozand P T
Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Clin Chem. 1997 Jul;43(7):1129-41.
Metabolic profiling of amino acids and acylcarnitines from blood spots by automated electrospray tandem mass spectrometry (ESI-MS/MS) is a powerful diagnostic tool for inborn errors of metabolism. New approaches to sample preparation and data interpretation have helped establish the methodology as a robust, high-throughput neonatal screening method. We introduce an efficient 96-well-microplate batch process for blood-spot sample preparation, with which we can obtain high-quality profiles from 500-1000 samples per day per instrument. A computer-assisted metabolic profiling algorithm automatically flags abnormal profiles. We selected diagnostic parameters for the algorithm by comparing profiles from patients with known metabolic disorders and those from normal newborns. Reference range and cutoff values for the diagnostic parameters were established by measuring either metabolite concentrations or peak ratios of certain metabolite pairs. Rigorous testing of the algorithm demonstrates its outstanding clinical sensitivity in flagging abnormal profiles and its high cumulative specificity.
通过自动电喷雾串联质谱法（ESI-MS/MS）对血斑中的氨基酸和酰基肉碱进行代谢谱分析，是诊断先天性代谢缺陷的有力工具。新的样品制备和数据解释方法有助于将该方法确立为一种强大的高通量新生儿筛查方法。我们介绍了一种用于血斑样品制备的高效96孔微孔板批量处理方法，使用该方法，每台仪器每天可从500 - 1000个样品中获得高质量的谱图。一种计算机辅助代谢谱分析算法会自动标记异常谱图。我们通过比较已知代谢紊乱患者和正常新生儿的谱图来选择该算法的诊断参数。通过测量代谢物浓度或某些代谢物对的峰比来确定诊断参数的参考范围和临界值。对该算法的严格测试证明了其在标记异常谱图方面具有出色的临床敏感性和高累积特异性。
