Clinical and Genetic Characteristics Associated With Survival Outcome in Late-Onset Huntington's Disease in South Korea

Background and Purpose The onset of Huntington's disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late -onset HD (LoHD) (age at onset >= 60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD. Methods Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected. Results Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77 +/- 5.91 years, mean +/- standard deviation; 40.54 +/- 1.53 mutant CAG repeats) and 61 with common -onset HD (CoHD) (AAO=44.12 +/- 8.61 years, 44.72 +/- 4.27 mutant CAG repeats). The ages at death were 77.78 +/- 7.46 and 53.72 +/- 10.86 years in patients with LoHD and CoHD, respectively (p< 0.001). The estimated survival time was 15.21 +/- 2.49 years for all HD patients, and 10.74 +/- 1.95 and 16.15 +/- 2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01-1.09, p=0.019; and HR=1.17, 95% CI=1.03-1.31, p=0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01-1.23, p=0.034) in the CoHD group. Conclusions Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD.