Lipidomic analysis of fibroblasts from Zellweger spectrum disorder patients identifies disease-specific phospholipid ratios.
Peroxisomes are subcellular organelles involved in various metabolic processes, including fatty acid and phospholipid homeostasis. The Zellweger spectrum disorders (ZSDs) represent a group of diseases caused by a defect in the biogenesis of peroxisomes. Accordingly, cells from ZSD patients are expected to have an altered composition of fatty acids and phospholipids. Using an LC/MS-based lipidomics approach, we show that the phospholipid composition is characteristically altered in cultured primary skin fibroblasts from ZSD patients when compared with healthy controls. We observed a marked overall increase of phospholipid species containing very long-chain fatty acids, and a decrease of phospholipid species with shorter fatty acid species in ZSD patient fibroblasts. In addition, we detected a distinct phosphatidylcholine profile in ZSD patients with a severe and mild phenotype when compared with control cells. Based on our data, we present a set of specific phospholipid ratios for fibroblasts that clearly discriminate between mild and severe ZSD patients, and those from healthy controls. Our findings will aid in the diagnosis and prognosis of ZSD patients, including an increasing number of mild patients in whom hardly any abnormalities are observed in biochemical parameters commonly used for diagnosis.
Laboratory Genetic Metabolic Diseases University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
Katharina
K
Herzog
Laboratory Genetic Metabolic Diseases University of Amsterdam, Amsterdam 1105 AZ, The Netherlands Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
Mia L
ML
Pras-Raves
Laboratory Genetic Metabolic Diseases University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
Martin A T
MA
Vervaart
Laboratory Genetic Metabolic Diseases University of Amsterdam, Amsterdam 1105 AZ, The Netherlands Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
Angela C M
AC
Luyf
Laboratory Genetic Metabolic Diseases University of Amsterdam, Amsterdam 1105 AZ, The Netherlands Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
Antoine H C
AH
van Kampen
Laboratory Genetic Metabolic Diseases University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
Ronald J A
RJ
Wanders
Laboratory Genetic Metabolic Diseases University of Amsterdam, Amsterdam 1105 AZ, The Netherlands f.m.vaz@amc.uva.nl h.r.waterham@amc.uva.nl.
Hans R
HR
Waterham
Laboratory Genetic Metabolic Diseases University of Amsterdam, Amsterdam 1105 AZ, The Netherlands f.m.vaz@amc.uva.nl h.r.waterham@amc.uva.nl.
Frédéric M
FM
Vaz
D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D055432:Metabolomics; D010743:Phospholipids / Q000378:metabolism*; D015211:Zellweger Syndrome / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D010743:Phospholipids
diagnosis; lipidomics; peroxisome biogenesis disorders; peroxisomes