Elevated CSF N-acetylaspartylglutamate suggests specific molecular diagnostic abnormalities in patients with white matter diseases.
BACKGROUND
In order to identify biomarkers useful for the diagnosis of genetic white matter disorders we compared the metabolic profile of patients with leukodystrophies with a hypomyelinating or a non-hypomyelinating MRI pattern.


METHODS
We used a non-a priori method of in vitro ¹H-NMR spectroscopy on CSF samples of 74 patients with leukodystrophies.


RESULTS
We found an elevation of CSF N-acetylaspartylglutamate (NAAG) in patients with Pelizaeus-Merzbacher disease (PMD)-PLP1 gene, Pelizaeus-Merzbacher-like disease-GJC2 gene and Canavan disease-ASPA gene. In the PMD group, NAAG was significantly elevated in the CSF of all patients with PLP1 duplication (19/19) but was strictly normal in 6 out of 7 patients with PLP1 point mutations. Additionally, we previously reported increased CSF NAAG in patients with SLC17A5 mutations.


CONCLUSIONS
Elevated CSF NAAG is a biomarker that suggests specific molecular diagnostic abnormalities in patients with white matter diseases. Our findings also point to unique pathological functions of the overexpressed PLP in PMD patients with duplication of this gene.
Mochel
Fanny
F
APHP, Department of Genetics, Hôpital de La Salpêtrière, Paris, France. fanny.mochel@upmc.fr
Boildieu
Nadège
N
Barritault
Julie
J
Sarret
Catherine
C
Eymard-Pierre
Eleonore
E
Seguin
François
F
Schiffmann
Raphael
R
Boespflug-Tanguy
Odile
O
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D017825:Canavan Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004151:Dipeptides / Q000134:cerebrospinal fluid* / Q000737:chemistry; D005260:Female; D020440:Gene Duplication; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D015394:Molecular Structure; D018991:Myelin Proteolipid Protein / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics; D020371:Pelizaeus-Merzbacher Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D017354:Point Mutation; D012680:Sensitivity and Specificity; D027981:Symporters / Q000235:genetics
D015415:Biomarkers; D004151:Dipeptides; D018991:Myelin Proteolipid Protein; D027361:Organic Anion Transporters; C472930:PLP1 protein, human; D027981:Symporters; C421224:sialic acid transport proteins; C027172:isospaglumic acid