title: Elevated CSF N-acetylaspartylglutamate in patients with free sialic acid storage diseases.
abstract: OBJECTIVE
  To investigate body fluids of patients with undiagnosed leukodystrophies using in vitro (1)H-NMR spectroscopy (H-NMRS).
  
  
  METHODS
  We conducted a cross-sectional study using high-resolution in vitro H-NMRS on CSF and urine samples.
  
  
  RESULTS
  We found a significant increase of free sialic acid in CSF or urine in 6 of 41 patients presenting with hypomyelination of unknown etiology. Molecular genetic testing revealed pathogenic mutations in the SLC17A5 gene in all 6 patients. H-NMRS revealed an increase of N-acetylaspartylglutamate in the CSF of all patients with SLC17A5 mutation (range 13-114 micromol/L, reference <12 micromol/L).
  
  
  CONCLUSIONS
  In patients with undiagnosed leukodystrophies, increased free sialic acid in CSF or urine is a marker for free sialic acid storage disorder and facilitates the identification of the underlying genetic defect. Because increase of N-acetylaspartylglutamate in CSF has been observed in other hypomyelinating disorders, it can be viewed as a marker of a subgroup of hypomyelinating disorders.
authors.affiliation: INSERM UMR S975, Hôpital de La Salpêtrière, Paris, France. fanny.mochel@upmc.fr
authors.forename: F
authors.initials: F
authors.lastname: Mochel
authors.forename: U F H
authors.initials: UF
authors.lastname: Engelke
authors.forename: J
authors.initials: J
authors.lastname: Barritault
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.forename: N H
authors.initials: NH
authors.lastname: McNeill
authors.forename: J N
authors.initials: JN
authors.lastname: Thompson
authors.forename: A
authors.initials: A
authors.lastname: Vanderver
authors.forename: N I
authors.initials: NI
authors.lastname: Wolf
authors.forename: M A
authors.initials: MA
authors.lastname: Willemsen
authors.forename: F W
authors.initials: FW
authors.lastname: Verheijen
authors.forename: F
authors.initials: F
authors.lastname: Seguin
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: R
authors.initials: R
authors.lastname: Schiffmann
mesh_terms: D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000652:urine; D004151:Dipeptides / Q000134:cerebrospinal fluid*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000134:cerebrospinal fluid / Q000652:urine; D027361:Organic Anion Transporters / Q000235:genetics*; D029461:Sialic Acid Storage Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D027981:Symporters / Q000235:genetics*; D055815:Young Adult
chemical_list: D004151:Dipeptides; D027361:Organic Anion Transporters; D027981:Symporters; C421224:sialic acid transport proteins; C027172:isospaglumic acid; D019158:N-Acetylneuraminic Acid