Weerd Jorine C van der, Wegberg Annemiek M J van, Boer Theo S, Engelke Udo F H, Coene Karlien L M, Wevers Ron A, Bakker Stephan J L, Blaauw Pim de, Groen Joost, Spronsen Francjan J van, Heiner-Fokkema M Rebecca
Department of Laboratory Medicine, Laboratory of Metabolic Disease, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Metabolites. 2024 Aug 30;14(9):479. doi: 10.3390/metabo14090479.
Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU).
To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann-Whitney U test, < 0.05) analyses.
Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated.
This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason.
数据表明，除血苯丙氨酸（Phe）外，其他代谢物能更好且独立地预测苯丙酮尿症（PKU）患者的临床结局。
为寻找新的生物标志物，我们将成年PKU患者经治疗后的非靶向脂质组学和代谢组学结果与匹配的对照组进行了比较。使用超高效液相色谱和高分辨率质谱分析样本（EDTA血浆中的脂质组学（22例PKU患者和22例对照）和血清中的代谢组学（35例PKU患者和20例对照））。数据进行多变量（主成分分析、正交偏最小二乘法判别分析）和单变量（曼-惠特尼U检验，<0.05）分析。
PKU患者与对照组之间，20443个脂质特征中的33个以及5885个代谢物特征中的56个在统计学上存在差异。脂质组学方面，发现甘油脂、甘油磷脂和鞘脂种类增加。甾醇和甘油磷脂种类的值显著降低。7个特征的身份未知。总甘油三酯含量较高。代谢组学方面，观察到苯丙氨酸及其分解代谢产物、色氨酸衍生物、泛酸和二肽水平较高。鸟氨酸水平较低。26个代谢物特征未注释。
本研究深入了解了PKU患者的代谢表型。需要进一步研究以确定观察到的变化是由PKU本身、饮食和/或未知原因导致的。
