Changes in the Cerebrospinal Fluid and Plasma Lipidome in Patients with Rett Syndrome
Martina Zandl-Lang,
Thomas Züllig,
Martin Trötzmüller,
Yvonne Naegelin,
Lucia Abela,
Bernd Wilken,
Sabine Scholl-Buergi,
Daniela Karall,
Ludwig Kappos,
Harald Köfeler,
Barbara Plecko
Affiliations
Martina Zandl-Lang
Department of Paediatrics and Adolescent Medicine, Division of General Paediatrics, University Childrens’ Hospital Graz, Medical University of Graz, 8036 Graz, Austria
Thomas Züllig
Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
Martin Trötzmüller
Core Facility Mass Spectrometry, Medical University of Graz, 8010 Graz, Austria
Yvonne Naegelin
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, 4031 Basel, Switzerland
Lucia Abela
Department of Child Neurology, University Children’s Hospital Zurich, 8032 Zurich, Switzerland
Bernd Wilken
Department of Pediatric Neurology, Klinikum Kassel, 34125 Kassel, Germany
Sabine Scholl-Buergi
Clinic for Paediatrics I, Inherited Metabolic Disorders, Medical, University of Innsbruck, 6020 Innsbruck, Austria
Daniela Karall
Clinic for Paediatrics I, Inherited Metabolic Disorders, Medical, University of Innsbruck, 6020 Innsbruck, Austria
Ludwig Kappos
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, 4031 Basel, Switzerland
Harald Köfeler
Core Facility Mass Spectrometry, Medical University of Graz, 8010 Graz, Austria
Barbara Plecko
Department of Paediatrics and Adolescent Medicine, Division of General Paediatrics, University Childrens’ Hospital Graz, Medical University of Graz, 8036 Graz, Austria
Rett syndrome (RTT) is defined as a rare disease caused by mutations of the methyl-CpG binding protein 2 (MECP2). It is one of the most common causes of genetic mental retardation in girls, characterized by normal early psychomotor development, followed by severe neurologic regression. Hitherto, RTT lacks a specific biomarker, but altered lipid homeostasis has been found in RTT model mice as well as in RTT patients. We performed LC-MS/MS lipidomics analysis to investigate the cerebrospinal fluid (CSF) and plasma composition of patients with RTT for biochemical variations compared to healthy controls. In all seven RTT patients, we found decreased CSF cholesterol levels compared to age-matched controls (n = 13), whereas plasma cholesterol levels were within the normal range in all 13 RTT patients compared to 18 controls. Levels of phospholipid (PL) and sphingomyelin (SM) species were decreased in CSF of RTT patients, whereas the lipidomics profile of plasma samples was unaltered in RTT patients compared to healthy controls. This study shows that the CSF lipidomics profile is altered in RTT, which is the basis for future (functional) studies to validate selected lipid species as CSF biomarkers for RTT.
