Simultaneous ALS and SCA2 associated with an intermediate-length <i>ATXN2</i> CAG-repeat expansion
Helia Ghahremani Nezhad, John Franklin, James J. P. Alix, Tobias Moll, M Pattrick, Johnathan Cooper‐Knock, Priya Shanmugarajah, Nick Beauchamp, Marios Hadjivissiliou, David Paling, Christopher McDermott, Pamela J. Shaw, Thomas M. Jenkins
Abstract
Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) share a common molecular basis: both are associated with CAG-repeat expansion of ATXN2 and TDP-43-positive neuronal cytoplasmic inclusions. To date, the two disorders are viewed as clinically distinct with ALS resulting from 30-33 CAG-repeats and SCA2 from >34 CAG-repeats. We describe a 67-year old with a 32 CAG-repeat expansion of ATXN2 who presented with simultaneous symptoms of ALS and SCA2. Our case demonstrates that the clinical dichotomy between SCA2 and ATXN2-ALS is false. We suggest instead that CAG-repeat expansion length determines the timing of SCA2 clinical symptoms relative to onset of ALS; consistent with this age of onset of SCA2 but not ATXN2-ALS, is dependent upon expansion length. Review of the literature and our local cohort provides evidence for occurrence of ALS in late stage SCA2, which may be under-recognised by clinicians who think of the two diseases as distinct.