title: Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA).
abstract: In order to identify new metabolic abnormalities in patients with complex neurodegenerative disorders of unknown aetiology, we performed high resolution in vitro proton nuclear magnetic resonance spectroscopy on patient cerebrospinal fluid (CSF) samples. We identified five adult patients, including two sisters, with significantly elevated free sialic acid in the CSF compared to both the cohort of patients with diseases of unknown aetiology (n = 144; P < 0.001) and a control group of patients with well-defined diseases (n = 91; P < 0.001). All five patients displayed cerebellar ataxia, with peripheral neuropathy and cognitive decline or noteworthy behavioural changes. Cerebral MRI showed mild to moderate cerebellar atrophy (5/5) as well as white matter abnormalities in the cerebellum including the peridentate region (4/5), and at the periventricular level (3/5). Two-dimensional gel analyses revealed significant hyposialylation of transferrin in CSF of all patients compared to age-matched controls (P < 0.001)--a finding not present in the CSF of patients with Salla disease, the most common free sialic acid storage disorder. Free sialic acid content was normal in patients' urine and cultured fibroblasts as were plasma glycosylation patterns of transferrin. Analysis of the ganglioside profile in peripheral nerve biopsies of two out of five patients was also normal. Sequencing of four candidate genes in the free sialic acid biosynthetic pathway did not reveal any mutation. We therefore identified a new free sialic acid syndrome in which cerebellar ataxia is the leading symptom. The term CAFSA is suggested (cerebellar ataxia with free sialic acid).
authors.affiliation: INSERM UMR S679, Hôpital de la Salpêtrière, 47 Bld de l'Hôpital, Bâtiment Nouvelle Pharmacie-4ème étage, 75013 Paris, France. fanny.mochel@upmc.fr
authors.forename: F
authors.initials: F
authors.lastname: Mochel
authors.forename: F
authors.initials: F
authors.lastname: Sedel
authors.forename: A
authors.initials: A
authors.lastname: Vanderver
authors.forename: U F H
authors.initials: UF
authors.lastname: Engelke
authors.forename: J
authors.initials: J
authors.lastname: Barritault
authors.forename: B Z
authors.initials: BZ
authors.lastname: Yang
authors.forename: B
authors.initials: B
authors.lastname: Kulkarni
authors.forename: D R
authors.initials: DR
authors.lastname: Adams
authors.forename: F
authors.initials: F
authors.lastname: Clot
authors.forename: J H
authors.initials: JH
authors.lastname: Ding
authors.forename: C R
authors.initials: CR
authors.lastname: Kaneski
authors.forename: F W
authors.initials: FW
authors.lastname: Verheijen
authors.forename: B W
authors.initials: BW
authors.lastname: Smits
authors.forename: F
authors.initials: F
authors.lastname: Seguin
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: M T
authors.initials: MT
authors.lastname: Vanier
authors.forename: M
authors.initials: M
authors.lastname: Huizing
authors.forename: R
authors.initials: R
authors.lastname: Schiffmann
authors.forename: A
authors.initials: A
authors.lastname: Durr
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000134:cerebrospinal fluid; D002478:Cells, Cultured; D002524:Cerebellar Ataxia / Q000134:cerebrospinal fluid* / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000134:cerebrospinal fluid*; D014168:Transferrin / Q000134:cerebrospinal fluid
chemical_list: D014168:Transferrin; D019158:N-Acetylneuraminic Acid