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

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 51; no. 11; pp. 2031 - 2042
• Main Authors: Vanderver, Adeline, Schiffmann, Raphael, Timmons, Margaret, Kellersberger, Katherine A, Fabris, Dan, Hoffman, Eric P, Maletkovic, Jelena, Hathout, Yetrib
• Format: Journal Article
• Language: English
• Published: Washington, DC Am Assoc Clin Chem 01.11.2005; American Association for Clinical Chemistry; Oxford University Press
• Subjects: Analytical, structural and metabolic biochemistry; Asialoglycoproteins - cerebrospinal fluid; Asialoglycoproteins - chemistry; Ataxia; Ataxia - cerebrospinal fluid; Ataxia - complications; Biological and medical sciences; Biomarkers; Central nervous system; Cerebrospinal fluid; Child; Children & youth; Electrophoresis, Gel, Two-Dimensional; Fourier transforms; Fundamental and applied biological sciences. Psychology; Glycopeptides - chemistry; Hereditary Central Nervous System Demyelinating Diseases - cerebrospinal fluid; Hereditary Central Nervous System Demyelinating Diseases - complications; Humans; Investigative techniques, diagnostic techniques (general aspects); Ionization; Lasers; Mass Spectrometry; Medical sciences; Mutation; Nervous system; Peptides; Protein Isoforms - cerebrospinal fluid; Proteins; Scientific imaging; Transferrin - analogs & derivatives; Transferrin - cerebrospinal fluid; Transferrin - chemistry; Human; Nervous system diseases; Spinocerebellar ataxia; Central nervous system disease; Clinical biology; Central nervous system; Degenerative disease; Biochemistry; Cerebrospinal fluid; Molecular biology; White matter; Genetic disease
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2005.055053

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. 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. 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. 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.