Metabolomics to study functional consequences in peroxisomal disorders

This thesis focusses on metabolomics approaches performed in cultured cells and blood samples from patients with peroxisomal disorders. By applying both targeted and untargeted metabolomics, the aim of these approaches was to study the functional consequences of the primary genetic defects causing peroxisomal disorders, and to investigate potential biomarkers.
Together, the work presented in this thesis demonstrates that a defect in peroxisome function results in consequences for cellular functions, which are not restricted to the peroxisome itself. Using lipidomics and metabolomics approaches, the results presented in this thesis show that the (phospho)lipid profiles determined in fibroblasts and plasma from patients with a peroxisomal disorder are profoundly altered. By developing a ratio method and targeted assays, novel biomarkers for diagnosis of patients with a peroxisomal defect were investigated. Finally, by expanding from metabolomics towards a multi-OMICS systems biology approach, new research opportunities for peroxisomal diseases were explored.