title: Elevated CSF N-acetylaspartylglutamate suggests specific molecular diagnostic abnormalities in patients with white matter diseases.
abstract: BACKGROUND
  In order to identify biomarkers useful for the diagnosis of genetic white matter disorders we compared the metabolic profile of patients with leukodystrophies with a hypomyelinating or a non-hypomyelinating MRI pattern.
  
  
  METHODS
  We used a non-a priori method of in vitro ¹H-NMR spectroscopy on CSF samples of 74 patients with leukodystrophies.
  
  
  RESULTS
  We found an elevation of CSF N-acetylaspartylglutamate (NAAG) in patients with Pelizaeus-Merzbacher disease (PMD)-PLP1 gene, Pelizaeus-Merzbacher-like disease-GJC2 gene and Canavan disease-ASPA gene. In the PMD group, NAAG was significantly elevated in the CSF of all patients with PLP1 duplication (19/19) but was strictly normal in 6 out of 7 patients with PLP1 point mutations. Additionally, we previously reported increased CSF NAAG in patients with SLC17A5 mutations.
  
  
  CONCLUSIONS
  Elevated CSF NAAG is a biomarker that suggests specific molecular diagnostic abnormalities in patients with white matter diseases. Our findings also point to unique pathological functions of the overexpressed PLP in PMD patients with duplication of this gene.
authors.affiliation: APHP, Department of Genetics, Hôpital de La Salpêtrière, Paris, France. fanny.mochel@upmc.fr
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
authors.forename: Nadège
authors.initials: N
authors.lastname: Boildieu
authors.forename: Julie
authors.initials: J
authors.lastname: Barritault
authors.forename: Catherine
authors.initials: C
authors.lastname: Sarret
authors.forename: Eleonore
authors.initials: E
authors.lastname: Eymard-Pierre
authors.forename: François
authors.initials: F
authors.lastname: Seguin
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D017825:Canavan Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004151:Dipeptides / Q000134:cerebrospinal fluid* / Q000737:chemistry; D005260:Female; D020440:Gene Duplication; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D015394:Molecular Structure; D018991:Myelin Proteolipid Protein / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics; D020371:Pelizaeus-Merzbacher Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D017354:Point Mutation; D012680:Sensitivity and Specificity; D027981:Symporters / Q000235:genetics
chemical_list: D015415:Biomarkers; D004151:Dipeptides; D018991:Myelin Proteolipid Protein; D027361:Organic Anion Transporters; C472930:PLP1 protein, human; D027981:Symporters; C421224:sialic acid transport proteins; C027172:isospaglumic acid