Heterogeneity in the Estimated Prevalence of Huntington’s Disease

There is significant variation in estimates of Huntington’s Disease (HD) prevalence in different settings. Despite this heterogeneity, there continues to be much interest in quantitatively synthesizing prevalence estimates to produce global or regional pooled prevalence values. This systematic review was undertaken to describe and assess the sources of heterogeneity in estimated prevalence values, and to consequently evaluate the validity of pooled prevalence values produced. Observational studies from which a prevalence estimate (point or period) or cumulative incidence of HD could be calculated between 1993-2024 were sought from Medline and Embase databases. Features of included studies are described and evaluated, with sources of heterogeneity discussed. A meta-regression was conducted including predictor variables: continent, median age of population, number of years since 1993, case ascertainment method, and Healthcare Access and Quality Index score. A total of 43 studies met the criteria for inclusion in the review. Significant clinical and methodological heterogeneity between the included studies is described, including differences in case definitions and ascertainment methods, and in the estimates of disease burden calculated. There were differences in the estimated point prevalence between regions and population groups within regions, while the estimated point prevalence was shown to be increasing over time since 1993. Wide prediction intervals in the overall pooled point prevalence (95% prediction interval: 0.32 – 37.55 cases per 100,000), and the European pooled point prevalence (95% prediction interval: 1.64 – 19.18 cases per 100,000), indicate the scale of heterogeneity between studies and settings. Such heterogeneity precludes valid extrapolation of findings to settings in which HD prevalence is unknown, and greatly limits the utility of pooled prevalence values.