OBJECTIVE: To investigate body fluids of patients with undiagnosed leukodystrophies using in vitro 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 μmol/L, reference <12 μmol/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.

, , , , , , , , , , , , , , , , , , ,
doi.org/10.1212/WNL.0b013e3181cbcdc4, hdl.handle.net/1765/19530
Erasmus MC: University Medical Center Rotterdam

Mochel, F., Engelke, U., Barritault, J., Yang, B., McNeill, N., Thompson, J. N., … Schiffmann, R. (2010). Elevated CSF N-acetylaspartylglutamate in patients with free sialic acid storage diseases. Neurology, 74(4), 302–305. doi:10.1212/WNL.0b013e3181cbcdc4