F08 Co-occurrence of amyotrophic lateral sclerosis and huntington’s disease – a systematic review

Abstract

Background While Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS) are clinically distinct neurodegenerative disorders, there have been reports of the co-occurrence of the two conditions in single individuals. Nonetheless, to our knowledge there has been no systematic review of the co-occurrence of HD and ALS to summarize the evidence to date. Aims 1) To systematically review the literature on the co-occurrence of HD and ALS in single individuals. 2) To examine the common features among the cases of individuals with HD and ALS. 3) To determine if the two disorders occurred together coincidentally or if they are causally related through an underlying mechanism. Methods A systematic review of all the literature on the co-occurrence of HD and ALS in single individuals – including case reports, observational studies, clinical trials, as well as mechanistic studies – until May 31, 2018 was performed, and descriptive analyses were conducted. Results Our searches have revealed 15 cases of individuals with confirmed diagnoses of both HD and ALS reported in the literature to date – and at least 5 other probable cases of HD and ALS. Among these 15 confirmed cases, the majority (13/15 cases) had an age of onset of HD symptoms between 40 and 72 years – generally higher than the average age of onset for individuals with HD without ALS. These cases had 39–47 CAG repeats in the Huntington gene – the lower end of the numbers of repeats in HD patients. More than half of these cases (9/15) had a diagnosis for ALS ranging from several months to years after the diagnosis of HD; 2/15 cases had a diagnosis of ALS before the diagnosis of HD (by 7 to 12 months); and 2/15 cases had ALS and HD diagnosed, or had symptoms of both, around the same time. There have been no observational studies or clinical trials on the co-occurrence of HD and ALS to date. Two mechanistic studies on the co-occurrence of HD and ALS were identified. Conclusion The number of reported cases on the co-occurrence of HD and ALS remains very low, which has rendered it highly challenging to conduct observational studies or clinical trials. Nonetheless, the current systematic review has revealed some common features among the reported cases, and has reviewed the proposed mechanisms of such co-occurrence. Further studies are warranted, and may be enhanced by the involvements of international consortia on HD and ALS.