Klemp Henry Gerd, Kettwig Matthias, Streit Frank, Gärtner Jutta, Rosewich Hendrik, Krätzner Ralph
Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Department of Clinical Chemistry, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Metabolites. 2021 May 29;11(6):347. doi: 10.3390/metabo11060347.
Peroxisomes are central hubs for cell metabolism and their dysfunction is linked to devastating human disorders, such as peroxisomal biogenesis disorders and single peroxisomal enzyme/protein deficiencies. For decades, biochemical diagnostics have been carried out using classical markers such as very long-chain fatty acids (VLCFA), which can be inconspicuous in milder and atypical cases. Holistic metabolomics studies revealed several potentially new biomarkers for peroxisomal disorders for advanced laboratory diagnostics including atypical cases. However, establishing these new markers is a major challenge in routine diagnostic laboratories. We therefore investigated whether the commercially available AbsoluteIDQ p180 kit (Biocrates Lifesciences), which utilizes flow injection and liquid chromatography mass spectrometry, may be used to reproduce some key results from previous global metabolomics studies. We applied it to serum samples from patients with mutations in peroxisomal target genes , , and the gene. Here we found various changes in sphingomyelins and lysophosphatidylcholines. In conclusion, this kit can be used to carry out extended diagnostics for peroxisomal disorders in routine laboratories, even without access to a metabolomics unit.
过氧化物酶体是细胞代谢的核心枢纽，其功能障碍与严重的人类疾病相关，如过氧化物酶体生物发生障碍和单一过氧化物酶/蛋白质缺乏症。几十年来，一直使用经典标志物（如极长链脂肪酸，VLCFA）进行生化诊断，在病情较轻和非典型病例中这些标志物可能并不明显。整体代谢组学研究揭示了几种潜在的新型生物标志物，可用于包括非典型病例在内的过氧化物酶体疾病的先进实验室诊断。然而，在常规诊断实验室中建立这些新标志物是一项重大挑战。因此，我们研究了市售的AbsoluteIDQ p180试剂盒（百趣生物科学公司），该试剂盒采用流动注射和液相色谱质谱联用技术，是否可用于重现先前全球代谢组学研究的一些关键结果。我们将其应用于过氧化物酶体靶基因、和基因发生突变的患者的血清样本。在此我们发现鞘磷脂和溶血磷脂酰胆碱有多种变化。总之，即使没有代谢组学设备，该试剂盒也可用于常规实验室对过氧化物酶体疾病进行扩展诊断。
