Received on May 26, 2005
Accepted on July 28, 2005

Proteomics and Protein Markers

Decreased Asialotransferrin in Cerebrospinal Fluid of Patients with Childhood-Onset Ataxia and Central Nervous System Hypomyelination/Vanishing White Matter Disease

¹ Children's National Medical Center, Children's Research Institute, Center for Genetic Medicine, Washington, DC
² Developmental and Metabolic Neurology Branch (DMNB), National Institute of Neurologic Disorders and Stroke (NINDS)/National Institutes of Health (NIH), Bethesda, MD
³ University of Maryland Baltimore County, Department of Chemistry and Biochemistry, Baltimore, MD

^* To whom correspondence should be addressed. E-mail: yhathout{at}cnmcresearch.org.

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 detected by 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 and efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.