Elevated CSF N-acetylaspartylglutamate in patients with free sialic acid storage diseases.
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.
Mochel
F
F
INSERM UMR S975, Hôpital de La Salpêtrière, Paris, France. fanny.mochel@upmc.fr
Engelke
U F H
UF
Barritault
J
J
Yang
B
B
McNeill
N H
NH
Thompson
J N
JN
Vanderver
A
A
Wolf
N I
NI
Willemsen
M A
MA
Verheijen
F W
FW
Seguin
F
F
Wevers
R A
RA
Schiffmann
R
R
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
D004151:Dipeptides; D027361:Organic Anion Transporters; D027981:Symporters; C421224:sialic acid transport proteins; C027172:isospaglumic acid; D019158:N-Acetylneuraminic Acid