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 hive clinical utility and pathophysiologic significance. Methods: We used 2-dimensional gel, electrophoresis/ miss spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/ VWM with that of unaffected controls. We characterised 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. Conclusion: 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 hive a significant impact on clinical studies exploring,new strategies for the management and treatment of this disease. (c) 2005 American Association for Clinical Chemistry.