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.

中文翻译：

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血浆 C24:0- 和 C26:0- 溶血磷脂酰胆碱是诊断过氧化物酶体 β-氧化性疾病的可靠生物标志物

过氧化物酶体疾病 (PD) 的金标准诊断测试是极长链脂肪酸 (VLCFA) 的血浆浓度分析。然而，这种方法非常耗时，而且在 VLCFA 水平正常的情况下也有局限性，因此需要其他方法。通过串联质谱 (MS/MS) 对干血斑样本中的 C26:0-溶血磷脂酰胆碱 (C26:0-LPC) 进行分析已成功应用于某些新生儿筛查项目，以诊断 X 连锁肾上腺脑白质营养不良 (ALD)。然而，人们对血浆中极长链 LPC 浓度的诊断潜力仍知之甚少。本研究旨在评估 C26:0-LPC 和其他超长链 LPC 的诊断性能，并将其与血浆中的 VLCFA 分析进行比较。该研究包括 330 名受过氧化物酶体 β-氧化缺陷影响的个体和 407 名对照个体，结果表明 C26:0- 和 C24:0-LPC 浓度表现出最高的诊断准确性（分别为 98.8% 和 98.4%），优于 VLCFA当 C26:0/C22:0 和 C24:0/C22:0 比率组合时 (98.1%)。组合 C24:0- 和 C26:0-LPC 的灵敏度最高 (99.7%)，与 VLCFA 比例组合相比，ALD 女性表现出明显更高的灵敏度（分别为 98.7% 和 93.5%）。相比之下，C22:0-LPC 表现出次优性能，主要是由于其敏感性较低 (75%)，但我们发现了一种潜在用途，可以帮助区分 ALD 和齐薇格谱系疾病。总之，与传统的 VLCFA 生物标志物相比，血浆 C24:0- 和 C26:0-LPC 浓度的 MS/MS 分析代表了一种快速、直接的诊断 PD 的方法，显示出卓越的诊断准确性，特别是在 ALD 女性中。我们强烈建议将超长链 LPC 血浆分析纳入疑似 PD 个体的诊断评估中。