Late-Onset Huntington's Disease in Mexico: A Retrospective Study

Background Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. It typically presents between the ages of 30 and 40 years. However, a small proportion of cases begin after the age of 60 years, which is referred to as late-onset Huntington's disease (LoHD). This study aimed to describe the main characteristics of LoHD patients identified at Mexico's leading neurological center. Methodology A retrospective, cross-sectional study was conducted by reviewing records from 1994 to mid-2024. The data collected included the patients' age, age at onset, diagnostic delay time, family history, molecular outcomes, clinical manifestations at onset, and total motor scores on the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS). Results From 1994 to mid-2024, the National Institute of Neurology and Neurosurgery Manuel Velasco Suárez reported 1,476 individuals with confirmed HD. Of those, 104 (7%) had LoHD, and 56.7% were female. The mean age of onset was 65.1 years. The mean age at molecular confirmation was 71.01 years. The mean diagnostic delay was 6.2 years. The origin of transmission was unknown in 41.3% of cases. Molecular testing revealed an average of 41.4 cytosine-adenine-guanine (CAG) repeats in the expanded allele. Motor symptoms were present at the beginning of the disease in 89% of cases. UHDRS-TMS showed a median score of 29. Conclusions LoHD is a rare form of HD with variable manifestations. A common finding in LoHD is the high proportion of patients with no family history of the disease. The lengths of the CAG expanded alleles are typically between 40 and 41 repeats. However, these lengths have also been observed in typical HD presentations. This suggests that further research is needed to identify possible modifiers and understand the pathways that delay disease onset.