PDF(Pubmed)
Abstract：
The gold-standard diagnostic test for peroxisomal disorders (PDs) is plasma concentration analysis of very long-chain fatty acids (VLCFAs). However, this method\'s time-consuming nature and limitations in cases which present normal VLCFA levels necessitates alternative approaches. The analysis of C26:0-lysophosphatydylcholine (C26:0-LPC) in dried blood spot samples by tandem-mass spectrometry (MS/MS) has successfully been implemented in certain newborn screening programs to diagnose X-linked adrenoleukodystrophy (ALD). However, the diagnostic potential of very long-chain LPCs concentrations in plasma remains poorly understood. This study sought to evaluate the diagnostic performance of C26:0-LPC and other very long-chain LPCs, comparing them to VLCFA analysis in plasma. The study, which included 330 individuals affected by a peroxisomal β-oxidation deficiency and 407 control individuals, revealed that C26:0- and C24:0-LPC concentrations demonstrated the highest diagnostic accuracy (98.8% and 98.4%, respectively), outperforming VLCFA when C26:0/C22:0 and C24:0/C22:0 ratios were combined (98.1%). Combining C24:0- and C26:0-LPC gave the highest sensitivity (99.7%), with ALD females exhibiting notably higher sensitivity compared with the VLCFA ratio combination (98.7% vs. 93.5%, respectively). In contrast, C22:0-LPC exhibited suboptimal performance, primarily due to its low sensitivity (75%), but we identified a potential use to help distinguish between ALD and Zellweger spectrum disorders. In summary, MS/MS analysis of plasma C24:0- and C26:0-LPC concentrations represents a rapid and straightforward approach to diagnose PDs, demonstrating superior diagnostic accuracy, particularly in ALD females, compared with conventional VLCFA biomarkers. We strongly recommend integrating very-long chain LPC plasma analysis in the diagnostic evaluation of individuals suspected of having a PD.
摘要：
过氧化物酶体紊乱（PD）的金标准诊断测试是非常长链脂肪酸（VLCFA）的血浆浓度分析。然而,这种方法的耗时性质和局限性，在呈现正常VLCFA水平的情况下，需要替代方法。通过串联质谱法（MS/MS）对干血斑样品中的C26：0-溶血磷酰胆碱（C26：0-LPC）的分析已在某些新生儿筛查计划中成功实施，以诊断X连锁肾上腺脑白质营养不良（ALD）。然而,血浆中长链LPCs浓度的诊断潜力尚不清楚.本研究旨在评估C26：0-LPC和其他非常长链LPC的诊断性能，将它们与血浆中的VLCFA分析进行比较。这项研究,其中包括330名受过氧化物酶体β-氧化缺乏症影响的个体和407名对照个体，显示C26：0-和C24：0-LPC浓度显示出最高的诊断准确性（分别为98.8％和98.4％），当C26:0/C22:0和C24:0/C22:0比率组合时(98.1%)优于VLCFA。结合C24:0-和C26:0-LPC给出了最高的灵敏度（99.7％），与VLCFA比率组合相比，ALD女性表现出明显更高的灵敏度(98.7%与93.5%,分别)。相比之下,C22:0-LPC表现出次优性能，主要是由于灵敏度低（75%），但是我们确定了一种潜在的用途来帮助区分ALD和Zellweger谱系障碍。总之,血浆C24：0-和C26：0-LPC浓度的MS/MS分析代表了诊断PD的快速和直接的方法，表现出卓越的诊断准确性，尤其是女性ALD，与常规VLCFA生物标志物相比。我们强烈建议在怀疑患有PD的个体的诊断评估中整合超长链LPC血浆分析。
