Decreased asialotransferrin in cerebrospinal fluid of patients with childhood-onset ataxia and central nervous system hypomyelination/vanishing white matter disease.
BACKGROUND
A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would have clinical utility and pathophysiologic significance.


METHODS
We used 2-dimensional gel electrophoresis/mass spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/VWM with that of unaffected controls. We characterized selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry.


RESULTS
A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and extraction, was found to be consistent with earlier reports.


CONCLUSIONS
The transferrin isoform abnormality in the cerebrospinal fluid of patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.
Vanderver
Adeline
A
Children's National Medical Center, Children's Research Institute, Center for Genetic Medicine, Washington, DC 20010, USA.
Schiffmann
Raphael
R
Timmons
Margaret
M
Kellersberger
Katherine A
KA
Fabris
Dan
D
Hoffman
Eric P
EP
Maletkovic
Jelena
J
Hathout
Yetrib
Y
D001212:Asialoglycoproteins / Q000134:cerebrospinal fluid* / Q000737:chemistry; D001259:Ataxia / Q000134:cerebrospinal fluid* / Q000150:complications; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D006020:Glycopeptides / Q000737:chemistry; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000150:complications; D006801:Humans; D013058:Mass Spectrometry; D020033:Protein Isoforms / Q000134:cerebrospinal fluid; D014168:Transferrin / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000737:chemistry
D001212:Asialoglycoproteins; D006020:Glycopeptides; D020033:Protein Isoforms; D014168:Transferrin; C017031:asialotransferrins