To investigate body fluids of patients with undiagnosed leukodystrophies using in vitro 1H-NMR spectroscopy (H-NMRS).
We conducted a cross-sectional study using high-resolution in vitro H-NMRS on CSF and urine samples.
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 μmol/L, reference <12 μmol/L).
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.
= correlation spectroscopy;
= glutamate carboxypeptidase II;
= 1H-NMR spectroscopy;
= infantile free sialic acid storage disease;
= free sialic acid storage disease.