Clinical And Molecular Features Of A Chinese Family With Spinocerebellar Ataxia Type6

Background:The spinocerebellar ataxias (SCA) is a large group of heterogeneous autosomal dominant degenerative diseases characterized by ataxia, often accompanied by degenerative changes in the brainstem and cerebellum, and other parts of the central nervous system(less commonly the peripheral nervous system, Basal ganglia and thalamus). Among SCA, the spinocerebellar ataxia type6accounts for about15%worldwide, most commonly in Japan, the Netherlands and Germany. In China, there are few case reports and lack of detailed epidemiological data. At present both domestic and international research focus on the gene mutation analysis of SCA6and there are almost no studies on mitochondrial function. It is significant to study whether there is mitochondrial dysfunction in SCA6, for better understanding of the pathophysiological mechanism and guidance on the treatment in the future.Objective:To evaluate the clinical manifestation, CAG repeats of abnormal alleles, mitochondrial function and treatment of spinocerebellar ataxia type6.Methods:We studied9patients from a family with spinocerebellar ataxias,4of whom had received molecular genetic testing for SCA1,2,3,6,7,12. Clinical and molecular features of SCA6were investigated. We also conducted muscle biopsy to evaluate mitochondrial function. Then4patients were treated with Idebenone and Butylphthalide, and measured the situation of improvement with scale for the assessment and rating of ataxia scores (SARA).Results:There were totally9patients showing slowly progressive ataxia without any remarkable extracerebellar signs in this family and the average age of onset was (40.25±8.76). At first,clinically, all patients showed ataxia of gait, then dysarthria and difficulty in swallowing. Brain CT or MRI showed atrophy of the cerebellum. All4patients were heterozygous and the number of CAG repeats in the expanded alleles was coincidentally the same21repeats and normal alleles in the SCA6gene ranged from4-18CAG units in healthy controls. Muscle biopsy was conducted in2patients and it showed mild muscle damage with mitochondrial dysfunction. Idebenone and Butylphthalide are effective in treatment for SCA6.Conclusions:We observe that CAG expansion in the SCA6family is completely stable. Clinical features are pure cerebellar impairment and mitochondrial dysfunction. Idebenone and Butylphthalide are effective in treatment for SCA6.