• cerebellar volume
• cortical volume
• fatigue
• magnetic resonance imaging
• spinocerebellar ataxia type 3 (Machado‐Joseph disease)

• Humans
• Male
• Machado-Joseph Disease/complications
• Machado-Joseph Disease/diagnostic imaging
• Machado-Joseph Disease/physiopathology
• Machado-Joseph Disease/genetics
• Female
• Middle Aged
• Fatigue/etiology
• Fatigue/epidemiology
• Fatigue/diagnostic imaging
• Fatigue/physiopathology
• Adult
• Magnetic Resonance Imaging
• Quality of Life
• Disease Progression
• Aged
• Prospective Studies
• Brain/diagnostic imaging
• Brain/pathology

• U21A20360 National Natural Science Foundation of China
• 2021Y9128 Joint Funds for the Innovation of Science and Technology of Fujian Province
• 2022ZQNZD005 Major Scientific Research Program for Young and Middle-aged Health Professionals of Fujian Province
• National Natural Science Foundation of China

• biomarker
• posture instability
• pre‐ataxic patients
• spinocerebellar ataxia type 3

• Humans
• Postural Balance/physiology
• Male
• Female
• Middle Aged
• Machado-Joseph Disease/physiopathology
• Machado-Joseph Disease/diagnosis
• Machado-Joseph Disease/complications
• Adult
• Aged

• 2023J01603 The Natural Science Fundation of Fujian Province
• 2022L3011 The Local Science and Technology Development Project
• 82230039 The National Natural Science Foundation of China
• 2021Y9128 The Innovation of Science and Technology of Fujian Province

Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease with high genetic heterogeneity. SCA3 mainly manifests as progressive cerebellar ataxia accompanied by paralysis of extraocular muscles, dysphagia, lingual fibrillation, pyramidal tract sign, and extrapyramidal system sign. However, it rarely has clinical manifestations similar to Parkinson-like symptoms, and is even rarer in patients sensitive to dopamine. We report a patient initially diagnosed with dopamine-responsive dystonia who was ultimately diagnosed with SCA3 by genetic testing, which was completely different from the initial diagnosis.

A 40-year-old Chinese woman was admitted to hospital due to severe inflexibility. At the beginning of the disease, she presented with anxiety and sleep disorder. At the later stage, she presented with gait disorder, which was similar to Parkinson's disease. Her medical history was unremarkable, but her mother, grandmother, and uncle all had similar illnesses and died due to inability to take care of themselves and related complications. Laboratory and imaging examinations showed no abnormalities, but electromyography and electroencephalography revealed delayed somatosensory evoked potentials and slow background rhythm, respectively. Her symptoms fluctuated during the daytime, and we initially diagnosed her with dopamine-responsive dystonia. After treatment with low-dose levodopa, the patient’s symptoms were significantly improved, but the final genetic diagnosis was SCA3.

SCA3 has various clinical phenotypes and needs to be differentiated from Parkinson's syndrome and dopamine-responsive dystonia.

• Spinocerebellar ataxia type 3
• Dopamine-responsive dystonia
• Gene phenotype
• Clinical phenotype
• Differential diagnosis
• Case report

Spinocerebellar ataxia type 3 (SCA3) is one of the most common hereditary neurodegenerative diseases, with balance instability as main symptom. Balance quantification is crucial for evaluating the efficacy of therapeutic interventions. However, balance evaluation in SCA3 is often subject to bias. Here, we aimed to quantitatively evaluate postural instability and investigate the relationship between postural instability and clinical characteristics in SCA3 patients.

Sixty‐two SCA3 patients and 62 normal controls were recruited, and their postural balance was measured using a posturographic platform. Principal component analysis was performed as data reduction to identify postural instability factors. Multivariable linear regression was used to investigate potential risk factors for postural instability and to explore whether postural instability predicts the severity and progression of ataxia in SCA3 patients.

We found SCA3 patients experience postural instability characterized by significant impairment in static and dynamic stability. The condition without visual feedback was the most sensitive measure in differentiating SCA3 from controls. Regression analyses revealed that ataxia severity predicted both static (P = 0.014) and dynamic stability (P = 0.001). Likewise, along with expanded CAG repeats (P < 0.001), both static (P < 0.001) and dynamic stability (P < 0.001) predicted ataxia severity, but not ataxia progression.

Our findings demonstrate the validity of using the Pro‐kin system for assessing postural instability in SCA3 patients. This type of quantitative assessment of balance dysfunction can contribute to clinical trials and balance rehabilitation in SCA3 patients.

Spinocerebellar ataxia type 3 (SCA3) is a rare, inherited form of ataxia that leads to progressive neurodegeneration. The initial symptoms could affect clinical phenotypes in neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis. However, the contribution of initial symptoms to the phenotypes of SCA3 has been scarcely investigated.

In the present study, 143 SCA3 patients from China were recruited and divided into two groups of gait‐onset and non‐gait‐onset. For determining the influences of initial symptoms on age at onset (AAO), the severity and progression of ataxia, and the possible factors affecting the initial symptoms, multivariable linear regression, and multivariate logistic regression were performed.

We found that the frequency of gait‐onset was 87.41%, and the frequency of non‐gait‐onset was 12.59% (diplopia: 7.69%, dysarthria: 4.20%, dystonia: 0.70%). Compared to the non‐gait‐onset group, the gait‐onset group had significantly more severe ataxia (p = 0.046), while the initial symptoms had no effect on AAO (p = 0.109) and progression of ataxia (p = 0.265). We failed to find the existence of any factors affecting initial symptoms.

These findings collectively suggested that initial symptoms influenced phenotypes in SCA3 and that neurodegeneration in different parts of brain may induce different disease severity in SCA3.

To investigate the contribution of initial symptoms to the phenotypes of spinocerebellar ataxia type 3 (SCA3), 143 SCA3 patients from China were recruited and divided into two groups of gait‐onset and non‐gait‐onset. We found that compared to the group of non‐gait‐onset, the group of gait‐onset had significantly more severe ataxia. Our finding suggested that initial symptoms influenced phenotypes in SCA3 and that neurodegeneration in different parts of brain may induce different severity in SCA3.

• initial symptoms
• neurodegeneration
• phenotypes
• spinocerebellar ataxia type 3