Huntington’s Disease: A Look at the Global Pace
—This updated systematic review and meta-analysis—the first in at least a decade—analyzed rates of this rare inherited neurological disorder in 21 countries, across multiple continents. Have rates gone up, down, or stayed the same?
Huntington’s disease (HD) is a rare neurological disorder that affects regions of the brain that control movements such as speaking, eating, and walking. Over time, cognitive changes—including problems with decision-making, problem-solving, attention, or judgment—may also develop. HD, which is inherited and affects adults mostly, can progress to involuntary, uncontrolled movements in the fingers, feet, face, or torso. Some of these symptoms can increase the risk of falls in this population.1
Past epidemiological studies on HD have shown a pooled incidence of 0.38 per 100,000 person-years and a global prevalence of 2.71 per 100,000 person-years.2 These numbers include patients who were diagnosed clinically and genetically. The clinical diagnosis is categorized as presymptomatic (patients have cytosine-adenine-guanine [CAG] expansion in the huntingtin gene [HTT] on genetic testing but no signs or symptoms of HD), prodromal (patients have CAG expansion and nonspecific or possible motor abnormalities with subtle but definitive cognitive changes), and manifest (patients have CAG expansion with motor abnormalities and minor or major neurocognitive changes).3
A few, more-recent studies have shown a slight increase in the prevalence of HD, possibly because of the “identification of different HTT gene haplotypes, healthcare accessibility, attitudes that differ on illness-related stigma, migration, and the identification of HD cluster regions, [in addition to] specific determinants [that] remain to be elucidated,” according to an updated systematic review and meta-analysis from a team of researchers based in Canada.3
The incidence and prevalence of HD: a fresh look
The studies included in this report were from North America, South America, Europe, Asia, Africa, and Oceania, which includes Australia, and were published between 2010 and 2022.3 Looking at the incidence of HD, the authors found that the pooled incidence from the studies was 0.48 per 100,000 person-years. In Europe, it was 0.38 per 100,000 person-years; in North America, it was 1.21 per 100,000 person-years; and, in Asia, it was much lower, at 0.06 per 100,000 person-years (this number was based on a single study, however). Five studies used only health administrative data to calculate incidence, rather than genetic testing or clinical criteria; without those studies, the pooled incidence estimate was 0.26 per 100,000 person-years.
To evaluate the prevalence of HD, the investigators looked at data from 21 countries: Brazil, Cameroon, Canada, Cyprus, Denmark, England, Finland, Germany, Greece, Iceland, Iran, Israel, Italy, Northern Ireland, Scotland, South Africa, South Korea, Spain, Sultanate of Oman, Sweden, and the U.S. The pooled prevalence of HD was 4.88 per 100,000 person-years.
Individual sub-analyses, by continent, showed the following rates of prevalence:
- South America (11.42 per 100,000 person-years)
- North America (8.87 per 100,000 person-years)
- Europe (6.37 per 100,000 person-years)
- Asia (2.39 per 100,000 person-years)
- Africa (0.25 per 100,000 person-years)
When the data were removed from the 5 prevalence studies that used only health administrative data for diagnosis, rather than genetic testing or clinical criteria, the pooled prevalence was 5.15 per 100,000 person-years.
Pooling older data with newer data
The authors then combined the current data with data from a 2012 review.2 The incidence of HD in the combined meta-analysis was 0.47 per 100,000 person-years. By continent, incidence rates per 100,000 person-years were as follows3:
- North America (1.04)
- Oceania (0.65)
- Europe (0.38)
- Asia (0.08)
The pooled prevalence of HD from the combined meta-analysis was 3.92 per 100,000. By continent, prevalence rates per 100,000 person-years were as follows:
- Oceania (8.61)
- North America (7.43)
- Europe (5.65)
- Asia (0.99)
- Africa (0.25)
When the authors compared the estimates from the initial study (1985 to 2010) to those from the current one (2011 to 2022), the prevalence of HD increased modestly over time, and the incidence rose only slightly. The authors attributed these increases to a combination of molecular testing availability; better recognition of HD by providers and patients (since HD can present in different ways), with subsequent earlier diagnosis; and better supportive care and treatment of patients’ comorbidities, which can improve mortality rates. Another underlying reason for the increase in the prevalence and incidence of HD is the occurrence of de novo HD mutations (which account for an estimated 7.1% of new cases).
What’s the bottom line?
“Overall, the present study suggests that there may be a small increase in both the global prevalence and incidence of HD since the previously performed systematic review and meta-analysis in 2012, but this increase is not statistically significant,” the authors wrote. “Although a similar proportion of the studies included for [the] meta-analysis used molecular testing as part of their case ascertainment criteria in the current review compared with 2012, the updated meta-analysis naturally includes additional and more recent studies incorporating genetic testing.”3
The authors suggested that future studies should use a variety of data sources and methods to capture cases of HD and explore its epidemiology with precision and accuracy.
“As HD is not a common disease, many individuals with HD receive care at regional centers of expertise, with diagnostic molecular testing performed at a single institution,” the authors concluded in their report. “Multisource ascertainment would permit further case validation studies to be performed and determine the sensitivity and specificity of diagnostic codes used in health administrative data to capture HD cases.”3
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