Elevated CSF N-acetylaspartylglutamate in patients with free sialic acid storage diseases

Neurology. 2010 Jan 26;74(4):302-5. doi: 10.1212/WNL.0b013e3181cbcdc4.


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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Demyelinating Diseases / cerebrospinal fluid*
  • Demyelinating Diseases / etiology
  • Demyelinating Diseases / urine
  • Dipeptides / cerebrospinal fluid*
  • Female
  • Genetic Testing
  • Genotype
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Mutation
  • N-Acetylneuraminic Acid / cerebrospinal fluid
  • N-Acetylneuraminic Acid / urine
  • Organic Anion Transporters / genetics*
  • Sialic Acid Storage Disease / cerebrospinal fluid*
  • Sialic Acid Storage Disease / complications
  • Sialic Acid Storage Disease / diagnosis*
  • Sialic Acid Storage Disease / genetics
  • Sialic Acid Storage Disease / urine
  • Symporters / genetics*
  • Young Adult


  • Dipeptides
  • Organic Anion Transporters
  • Symporters
  • sialic acid transport proteins
  • isospaglumic acid
  • N-Acetylneuraminic Acid