title: A novel, highly sensitive and specific biomarker for Niemann-Pick type C1 disease.
abstract: BACKGROUND
  Lysosomal storage disorders (LSDs), are a heterogeneous group of rare disorders caused by defects in genes encoding for proteins involved in the lysosomal degradation of macromolecules. They occur at a frequency of about 1 in 5,000 live births, though recent neonatal screening suggests a higher incidence. New treatment options for LSDs demand a rapid, early diagnosis of LSDs if maximal clinical benefit is to be achieved.
  
  
  METHODS
  Here, we describe a novel, highly specific and sensitive biomarker for Niemann-Pick Type C disease type 1 (NPC1), lyso-sphingomyelin-509. We cross-validate this biomarker with cholestane-3β,5α,6β-triol and relative lysosomal volume. The primary cohort for establishment of the biomarker contained 135 NPC1 patients, 66 NPC1 carriers, 241 patients with other LSDs and 46 healthy controls.
  
  
  RESULTS
  With a sensitivity of 100.0% and specificity of 91.0% a cut-off of 1.4 ng/ml was established. Comparison with cholestane-3β,5α,6β-triol and relative acidic compartment volume measurements were carried out with a subset of 125 subjects. Both cholestane-3β,5α,6β-triol and lyso-Sphingomyelin-509 were sufficient in establishing the diagnosis of NPC1 and correlated with disease severity.
  
  
  CONCLUSIONS
  In summary, we have established a new biomarker for the diagnosis of NPC1, and further studies will be conducted to assess correlation to disease progress and monitoring treatment.
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Medical University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany. anne-katrin.giese@med.uni-rostock.de.
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Giese
authors.affiliation: PharmAnalyt Labor GmbH, Ferdinand-Pichler Gasse 2, 2500, Baden, Austria. hermann.mascher@pharm-analyt.at.
authors.forename: Hermann
authors.initials: H
authors.lastname: Mascher
authors.affiliation: Department for Biostatistics and Clinical Epidemiology, Charité-University Medical Centre, Berlin, Germany. ulrike.grittner@charite.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Grittner
authors.affiliation: Centogene AG, Schillingallee 68, 18055, Rostock, Germany. sabrina.eichler@centogene.de.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Eichler
authors.affiliation: Centogene AG, Schillingallee 68, 18055, Rostock, Germany. Guido.Kramp@centogene.com.
authors.forename: Guido
authors.initials: G
authors.lastname: Kramp
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Medical University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany. jan.lukas@med.uni-rostock.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Lukas
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. danielle.tevruchte@pharm.ox.ac.uk.
authors.forename: Danielle
authors.initials: D
authors.lastname: te Vruchte
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. nada.aleisa@wolfson.ox.ac.uk.
authors.forename: Nada
authors.initials: N
authors.lastname: Al Eisa
authors.affiliation: Population, Policy and Practice Programme, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK. m.cortina@ucl.ac.uk.
authors.forename: Mario
authors.initials: M
authors.lastname: Cortina-Borja
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA. fdporter@mail.nih.gov.
authors.forename: Forbes D
authors.initials: FD
authors.lastname: Porter
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. frances.platt@pharm.ox.ac.uk.
authors.forename: Frances M
authors.initials: FM
authors.lastname: Platt
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Medical University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany. arndt.rolfs@med.uni-rostock.de.|Centogene AG, Schillingallee 68, 18055, Rostock, Germany. arndt.rolfs@med.uni-rostock.de.
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052556:Niemann-Pick Disease, Type C / Q000097:blood* / Q000175:diagnosis*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D013110:Sphingosine