Lc-ms based platform simplifies access to metabolomics for peroxisomal disorders

Abstract

Peroxisomes are central hubs for cell metabolism and their dysfunction is linked to dev-astating human disorders, such as peroxisomal biogenesis disorders and single peroxisomal en-zyme/protein deficiencies. For decades, biochemical diagnostics have been carried out using classi-cal 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 pe-roxisomal disorders for advanced laboratory diagnostics including atypical cases. However, estab-lishing these new markers is a major challenge in routine diagnostic laboratories. We therefore in-vestigated whether the commercially available AbsoluteIDQ p180 kit (Biocrates Lifesciences), which utilizes flow injection and liquid chromatography mass spectrometry, may be used to repro-duce some key results from previous global metabolomics studies. We applied it to serum samples from patients with mutations in peroxisomal target genes PEX1, ABCD1, and the HSD17B4 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 labora-tories, even without access to a metabolomics unit.