期刊
BRAIN
卷 132, 期 -, 页码 801-809出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awn355
关键词
cerebellar ataxia; free sialic acid; cerebrospinal fluid; neurometabolic disorder; nuclear magnetic resonance spectroscopy
资金
- Assistance Publique des Hopitaux de Paris [CRC 05169]
- Intramural Program of the National Institute of Neurological Disorders and Stroke
- National Human Genome Research Institute
- National Institute of Health
- Baylor Research Foundation
- Integrated Molecular Core for Rehabilitation Medicine
- NIH IDDRC [P30HD40677]
- NIH NCMRR/NINDS [5R24 HD050846]
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).
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