title: N(8)-acetylspermidine as a potential plasma biomarker for Snyder-Robinson syndrome identified by clinical metabolomics.
abstract: Clinical metabolomics has emerged as a powerful tool to study human metabolism in health and disease. Comparative statistical analysis of untargeted metabolic profiles can reveal perturbations of metabolite levels in diseases and thus has the potential to identify novel biomarkers. Here we have applied a simultaneous genetic-metabolomic approach in twin boys with epileptic encephalopathy of unclear etiology. Clinical exome sequencing identified a novel missense mutation in the spermine synthase gene (SMS) that causes Snyder-Robinson syndrome (SRS). Untargeted plasma metabolome analysis revealed significantly elevated levels of N(8)-acetylspermidine, a precursor derivative of spermine biosynthesis, as a potential novel plasma biomarker for SRS. This result was verified in a third patient with genetically confirmed SRS. This study illustrates the potential of metabolomics as a translational technique to support exome data on a functional and clinical level.
authors.affiliation: Division of Child Neurology, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Children's Research Centre, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Abela
authors.affiliation: Division of Child Neurology, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Children's Research Centre, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.
authors.forename: Luke
authors.initials: L
authors.lastname: Simmons
authors.affiliation: Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Institute of Medical Genetics, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Steindl
authors.affiliation: Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Division of Epilepsy and Neurophysiology, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmitt
authors.affiliation: Pediatric Neurology Unit, V. Buzzi Children's Hospital, ICP, Via Castelvetro 24, 20154, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mastrangelo
authors.affiliation: Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Institute of Medical Genetics, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Joset
authors.affiliation: Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Institute of Medical Genetics, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Papuc
authors.affiliation: Institute for Biochemistry, University of Erlangen-Nuernberg, Fahrstrasse 17, 91054, Erlangen, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sticht
authors.affiliation: Institute of Medical Genetics, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baumer
authors.affiliation: Division of Child Neurology, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Children's Research Centre, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Crowther
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.
authors.forename: Déborah
authors.initials: D
authors.lastname: Mathis
authors.affiliation: Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.|Institute of Medical Genetics, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.affiliation: Division of Child Neurology, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland. barbara.plecko@kispi.uzh.ch.|Children's Research Centre, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland. barbara.plecko@kispi.uzh.ch.|Radiz-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland. barbara.plecko@kispi.uzh.ch.
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D038901:X-Linked Intellectual Disability / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D055442:Metabolome / Q000235:genetics; D055432:Metabolomics / Q000379:methods; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010949:Plasma / Q000378:metabolism*; D013095:Spermidine / Q000031:analogs & derivatives* / Q000097:blood; D013097:Spermine Synthase / Q000235:genetics
chemical_list: D015415:Biomarkers; C030223:N(8)-acetylspermidine; D013097:Spermine Synthase; D013095:Spermidine