Prevalence of Juvenile-Onset and pediatric Huntington's Disease and their availability and ability to participate in trials: a Dutch population and Enroll-HD observational study

Abstract

Background: Juvenile-onset Huntington’s disease (JHD) represents 1–5% of Huntington’s disease (HD) patients, with onsetbefore the age of 21. Pediatric HD (PHD) relates to a proportion of JHD patients that is still under 18 years of age. So far,both populations have been excluded from interventional trials.Objective: Describe the prevalence and incidence of JHD and PHD in the Netherlands and explore their ability to participatein interventional trials.Methods: The prevalence and incidence of PHD and JHD patients in the Netherlands were analyzed. In addition, weexplored proportions of JHD patients diagnosed at pediatric versus adult age, their diagnostic delay, and functional andmodelled (CAP 100 ) disease stage in JHD and adult-onset HD patients at diagnosis.Results: The prevalence of JHD and PHD relative to the total manifest HD population in January 2024 was between0.84–1.25% and 0.09–0.14% respectively. The mean incidence of JHD patients being diagnosed was between 0.85–1.28 per1000 patient years and of PHD 0.14 per 1.000.000 under-aged person years. 55% of JHD cases received a clinical diagnosison adult age. At diagnosis, the majority of JHD patients was functionally compromised and adolescent-onset JHD patientswere significantly less independent compared to adult-onset HD patients.Conclusions: In the Netherlands, the epidemiology of JHD and PHD is lower than previously suggested. More than halfof JHD cases are not eligible for trials in the PHD population. Furthermore, higher functional dependency in JHD patientsinfluences their ability to participate in trials. Lastly, certain UHDRS functional assessments and the CAP 100 score do notseem appropriate for this particular group.