title: Decreased asialotransferrin in cerebrospinal fluid of patients with childhood-onset ataxia and central nervous system hypomyelination/vanishing white matter disease.
abstract: BACKGROUND
  A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would have clinical utility and pathophysiologic significance.
  
  
  METHODS
  We used 2-dimensional gel electrophoresis/mass spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/VWM with that of unaffected controls. We characterized selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry.
  
  
  RESULTS
  A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and extraction, was found to be consistent with earlier reports.
  
  
  CONCLUSIONS
  The transferrin isoform abnormality in the cerebrospinal fluid of patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.
authors.affiliation: Children's National Medical Center, Children's Research Institute, Center for Genetic Medicine, Washington, DC 20010, USA.
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Margaret
authors.initials: M
authors.lastname: Timmons
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Kellersberger
authors.forename: Dan
authors.initials: D
authors.lastname: Fabris
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: Jelena
authors.initials: J
authors.lastname: Maletkovic
authors.forename: Yetrib
authors.initials: Y
authors.lastname: Hathout
mesh_terms: D001212:Asialoglycoproteins / Q000134:cerebrospinal fluid* / Q000737:chemistry; D001259:Ataxia / Q000134:cerebrospinal fluid* / Q000150:complications; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D006020:Glycopeptides / Q000737:chemistry; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000150:complications; D006801:Humans; D013058:Mass Spectrometry; D020033:Protein Isoforms / Q000134:cerebrospinal fluid; D014168:Transferrin / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000737:chemistry
chemical_list: D001212:Asialoglycoproteins; D006020:Glycopeptides; D020033:Protein Isoforms; D014168:Transferrin; C017031:asialotransferrins