Objective: To characterise the clinical and pathologic findings of Huntington’s disease (HD) and coincident amyotrophic lateral sclerosis (ALS).

Background: A 66 year old man presented with chorea and was found to have fasciculations and weakness. He was ultimately diagnosed with genetically confirmed HD and sporadic ALS. We have identified only 11 similar published cases, although chorea and ALS may coexist in other conditions.

Methods: A 66 year-old man presented with falls, clumsiness and involuntary movements. On examination, there were intermittent phonic tics, generalised chorea, wasting, fasciculations and weakness with hyperreflexia. He was dysphagic, hypophonic and dysarthric with choreic tongue and facial movements, reduced palatal elevation and repetitive sniffing. There was impersistence of gaze and slowed saccades. Cognitive impairment, with predominantly frontal lobe involvement, was present.

Results: MRI brain demonstrated mild caudate atrophy. Interval EMG/NCS was consistent with a widespread anterior horn cell disorder. Genetic testing revealed one allele 40 CAG repeats in the huntingtin gene and C9orf72 mutation was not found. Our patient ultimately died due to respiratory insufficiency. Post mortem examination confirmed a diagnosis of ALS with TDP-43 inclusions in the anterior horn cells of the spinal cord, and in nuclei in the medulla. There was gross caudate atrophy with neuronal loss and striatal gliosis.

Conclusions: The risk of both HD and ALS occurring in the same individual could be as low as four persons per billion. Ours is the second case to be reported in Ireland; more than would be expected by chance alone. Their co-occurrence poses unique challenges in genetic counselling, medical care and social supports. HD is not the only polyglutamine disorder to be linked with ALS, however. In spinocerebellar ataxia (SCA) 3, for example, TDP-43 inclusions were demonstrated in the LMN of brainstem and spinal cord(1) and intermediate expansions of the polyglutamine associated with SCA2, have been reported as a genetic risk factor for ALS(2). Could polyglutamine aggregation and toxicity lead to neuronal cell loss in genetically susceptible individuals? Although rare, recognition of the association of HD and ALS is important to facilitate appropriate care and may, through post mortem studies, shed light on aetiopathologic links.

References: 1. Tan C-F, Yamada M, Toyoshima Y, Yokoseki A, Miki Y, Hoshi Y, et al. Selective occurrence of TDP-43-immunoreactive inclusions in the lower motor neurons in Machado-Joseph disease. Acta Neuropathol [Internet]. 2009 Oct 13 [cited 2017 Aug 13];118(4):553–60. Available from: http://link.springer.com/10.1007/s00401-009-0552-x. 2. Elden AC, Kim H-J, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature [Internet]. 2010 Aug 26 [cited 2017 Aug 13];466(7310):1069–75. Available from: http://www.nature.com/doifinder/10.1038/nature09320.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/on-the-hunt-for-a-link-between-genetically-confirmed-huntingtons-disease-and-amyotrophic-lateral-sclerosis/