Jaspers Yorrick R J, Ferdinandusse Sacha, Dijkstra Inge M E, Barendsen Rinse Willem, van Lenthe Henk, Kulik Wim, Engelen Marc, Goorden Susan M I, Vaz Frédéric M, Kemp Stephan
Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, University of Amsterdam, Amsterdam, Netherlands.
Department of Pediatric Neurology, Amsterdam UMC, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands.
Front Cell Dev Biol. 2020 Jul 29;8:690. doi: 10.3389/fcell.2020.00690. eCollection 2020.
Peroxisomes are subcellular organelles that are involved in various important physiological processes such as the oxidation of fatty acids and the biosynthesis of bile acids and plasmalogens. The gold standard in the diagnostic work-up for patients with peroxisomal disorders is the analysis of very long-chain fatty acid (VLCFA) levels in plasma. Alternatively, C26:0-lysophosphatidylcholine (C26:0-LPC) can be measured in dried blood spots (DBS) using liquid chromatography tandem mass spectrometry (LC-MS/MS); a fast and easy method but not yet widely used. Currently, little is known about the correlation of C26:0-LPC in DBS and C26:0-LPC in plasma, and how C26:0-LPC analysis compares to VLCFA analysis in diagnostic performance. We investigated the correlation between C26:0-LPC levels measured in DBS and plasma prepared from the same blood sample. For this analysis we included 43 controls and 38 adrenoleukodystrophy (ALD) (21 males and 17 females) and 33 Zellweger spectrum disorder (ZSD) patients. In combined control and patient samples there was a strong positive correlation between DBS C26:0-LPC and plasma C26:0-LPC, with a Spearman's rank correlation coefficient of (114) = 0.962, < 0.001. These data show that both plasma and DBS are suitable to determine blood C26:0-LPC levels and that there is a strong correlation between C26:0-LPC levels in both matrices. Following this, we investigated how VLCFA and C26:0-LPC analysis compare in diagnostic performance for 67 controls, 26 ALD males, 19 ALD females, and 35 ZSD patients. For C26:0-LPC, all ALD and ZSD samples had C26:0-LPC levels above the upper limit of the reference range. For C26:0, one out of 67 controls had C26:0 levels above the upper reference range. For 1 out of 26 (1/26) ALD males, 1/19 ALD females and 3/35 ZSD patients, the C26:0 concentration was within the reference range. The C26:0/C22:0 ratio was within the reference range for 0/26 ALD males, 1/19 ALD females and 2/35 ZSD patients. Overall, these data demonstrate that C26:0-LPC analysis has a superior diagnostic performance compared to VLCFA analysis (C26:0 and C26:0/C22:0 ratio) in all patient groups. Based on our results we recommend implementation of C26:0-LPC analysis in DBS and/or plasma in the diagnostic work-up for peroxisomal disorders.
过氧化物酶体是亚细胞细胞器，参与多种重要的生理过程，如脂肪酸氧化、胆汁酸生物合成和缩醛磷脂的生物合成。对过氧化物酶体疾病患者进行诊断检查的金标准是分析血浆中极长链脂肪酸（VLCFA）水平。另外，可使用液相色谱串联质谱法（LC-MS/MS）在干血斑（DBS）中检测C26:0-溶血磷脂酰胆碱（C26:0-LPC）；这是一种快速简便的方法，但尚未广泛应用。目前，对于DBS中的C26:0-LPC与血浆中的C26:0-LPC之间的相关性，以及C26:0-LPC分析在诊断性能方面与VLCFA分析相比情况知之甚少。我们研究了在DBS中测得的C26:0-LPC水平与从同一血样制备的血浆中C26:0-LPC水平之间的相关性。为此分析，我们纳入了43名对照者、38名肾上腺脑白质营养不良（ALD）患者（21名男性和17名女性）以及33名泽尔韦格谱系障碍（ZSD）患者。在对照者和患者的合并样本中，DBS中的C26:0-LPC与血浆中的C26:0-LPC之间存在强正相关，斯皮尔曼等级相关系数为（114）=0.962，P<0.001。这些数据表明，血浆和DBS都适合用于测定血液中C26:0-LPC水平，且两种基质中C26:0-LPC水平之间存在强相关性。在此之后，我们研究了VLCFA和C26:0-LPC分析在67名对照者、26名ALD男性、19名ALD女性和35名ZSD患者的诊断性能方面的比较情况。对于C26:0-LPC，所有ALD和ZSD样本的C26:0-LPC水平均高于参考范围上限。对于C26:0，67名对照者中有1名的C26:0水平高于参考范围上限。对于26名ALD男性中的1名、19名ALD女性中的1名以及35名ZSD患者中的3名，C26:浓缩0度在参考范围内。对于0/26名ALD男性、1/19名ALD女性和2/35名ZSD患者，C26:0/C22:0比值在参考范围内。总体而言，这些数据表明，在所有患者组中，C26:0-LPC分析在诊断性能方面优于VLCFA分析（C26:0和C26:0/C22:0比值）。基于我们的结果，我们建议在过氧化物酶体疾病的诊断检查中，在DBS和/或血浆中实施C26:0-LPC分析。
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