Simultaneous ALS and SCA2 associated with an intermediate-length ATXN2 CAG-repeat expansion

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) share molecular underpinnings, including ATXN2 CAG-repeat expansions and TDP-43 inclusions.
• Current understanding posits distinct clinical presentations based on CAG-repeat length: 30-33 repeats for ALS and >34 for SCA2.

Purpose of the Study:

• To investigate the clinical overlap between SCA2 and ATXN2-ALS.
• To challenge the established clinical dichotomy between SCA2 and ATXN2-ALS.
• To explore the role of CAG-repeat expansion length in disease manifestation timing.

Main Methods:

• Case study of a 67-year-old patient with a 32 CAG-repeat expansion in ATXN2 presenting with concurrent ALS and SCA2 symptoms.
• Review of existing literature and local patient cohort data.

Main Results:

• The described patient exhibited simultaneous ALS and SCA2 symptoms despite having 32 CAG-repeats, a length typically associated with ALS.
• Evidence suggests that CAG-repeat expansion length influences the onset timing of SCA2 symptoms relative to ALS.
• ALS has been observed in late-stage SCA2 patients, indicating a potential under-recognition of this overlap.

Conclusions:

• The clinical distinction between SCA2 and ATXN2-ALS is not absolute, as demonstrated by the presented case.
• CAG-repeat expansion length in ATXN2 is a critical factor in determining the clinical phenotype and symptom onset.
• Clinicians should consider the possibility of ALS in patients with advanced SCA2, and vice versa, to improve diagnosis and management.