The Natural History of Spinocerebellar Ataxia Type 3 in Mainland China: A 2-Year Cohort Study

Yun Peng; Linliu Peng; Zhao Chen; Huirong Peng; Puzhi Wang; Youming Zhang; Yangping Li; Chunrong Wang; Yuting Shi; Xuan Hou; Zhe Long; Hongyu Yuan; Na Wan; Linlin Wan; Keqin Xu; Lijing Lei; Shang Wang; Lang He; Yue Xie; Yiqing Gong; Qi Deng; Guangdong Zou; Zhichao Tang; Lu Shen; Kun Xia; Rong Qiu; Thomas Klockgether; Beisha Tang; Hong Jiang

doi:10.3389/fnagi.2022.917126

The Natural History of Spinocerebellar Ataxia Type 3 in Mainland China: A 2-Year Cohort Study

Front Aging Neurosci. 2022 Jul 5:14:917126. doi: 10.3389/fnagi.2022.917126. eCollection 2022.

Authors

Yun Peng¹, Linliu Peng¹, Zhao Chen¹, Huirong Peng¹, Puzhi Wang¹, Youming Zhang², Yangping Li³, Chunrong Wang⁴, Yuting Shi¹, Xuan Hou¹, Zhe Long⁵, Hongyu Yuan¹, Na Wan¹, Linlin Wan¹, Keqin Xu¹, Lijing Lei¹, Shang Wang¹, Lang He¹, Yue Xie¹, Yiqing Gong¹, Qi Deng¹, Guangdong Zou¹, Zhichao Tang¹, Lu Shen^{1

6

7

8

9}, Kun Xia⁶, Rong Qiu¹⁰, Thomas Klockgether^{11

12}, Beisha Tang^{1

6

7

8

9}, Hong Jiang^{1

6

7

8

9}

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
² Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, United States.
⁴ Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
⁶ Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
⁷ National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, China.
⁸ Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
⁹ Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China.
¹⁰ School of Computer Science and Engineering, Central South University, Changsha, China.
¹¹ Department of Neurology, University of Bonn, Bonn, Germany.
¹² German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Abstract

Objective: The natural history of spinocerebellar ataxia type 3 (SCA3) has been reported in several populations and shows heterogeneity in progression rate and affecting factors. However, it remains unexplored in the population of Mainland China. This study aimed to identify the disease progression rate and its potential affecting factors in patients with SCA3 in Mainland China.

Participants and methods: We enrolled patients with genetically confirmed SCA3 in Mainland China. Patients were seen at three visits, i.e., baseline, 1 year, and 2 years. The primary outcome was the Scale for the Assessment and Rating of Ataxia (SARA), and the secondary outcomes were the Inventory of Non-Ataxia Signs (INAS) as well as the SCA Functional Index (SCAFI).

Results: Between 1 October 2015, and 30 September 2016, we enrolled 263 patients with SCA3. We analyzed 247 patients with at least one follow-up visit. The annual progression rate of SARA was 1.49 points per year (SE 0.08, 95% confidence interval [CI] 1.33-1.65, p < 0.0001). The annual progression rates of INAS and SCAFI were 0.56 points per year (SE 0.05, 95% CI 0.47-0.66, p < 0.001) and -0.30 points per year (SE 0.01, 95% CI -0.33∼-0.28, p < 0.001), respectively. Faster progression in SARA was associated with longer length of the expanded allele of ATXN3 (p < 0.0001); faster progression in INAS was associated with lower INAS at baseline (p < 0.0001); faster decline in SCAFI was associated with shorter length of the normal allele of ATXN3 (p = 0.036) and higher SCAFI at baseline (p < 0.0001).

Conclusion: Our results provide quantitative data on the disease progression of patients with SCA3 in Mainland China and its corresponding affecting factors, which could facilitate the sample size calculation and patient stratification in future clinical trials.

Trial registration: This study was registered with Chictr.org on 15 September 2015, number ChiCTR-OOC-15007124.

Keywords: ATXN3; Machado-Joseph disease (MJD); disease progression; natural history; spinocerebellar ataxia type 3.