Comparison of the Diagnostic Performance of C26:0-Lysophosphatidylcholine and Very Long-Chain Fatty Acids Analysis for Peroxisomal Disorders.

ABSTRACT

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, C260-lysophosphatidylcholine (C260-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 C260-LPC in DBS and C260-LPC in plasma, and how C260-LPC analysis compares to VLCFA analysis in diagnostic performance. We investigated the correlation between C260-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 C260-LPC and plasma C260-LPC, with a Spearman's rank correlation coefficient of r (114) = 0.962, p < 0.001. These data show that both plasma and DBS are suitable to determine blood C260-LPC levels and that there is a strong correlation between C260-LPC levels in both matrices. Following this, we investigated how VLCFA and C260-LPC analysis compare in diagnostic performance for 67 controls, 26 ALD males, 19 ALD females, and 35 ZSD patients. For C260-LPC, all ALD and ZSD samples had C260-LPC levels above the upper limit of the reference range. For C260, one out of 67 controls had C260 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 C260 concentration was within the reference range. The C260/C220 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 C260-LPC analysis has a superior diagnostic performance compared to VLCFA analysis (C260 and C260/C220 ratio) in all patient groups. Based on our results we recommend implementation of C260-LPC analysis in DBS and/or plasma in the diagnostic work-up for peroxisomal disorders.