Economic burden of Huntington’s disease: A systematic review

Abstract

Background

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease, characterized by progressive motor, cognitive, and psychiatric symptoms. The disease poses a significant social and economic burden.

Objective

This systematic review aims to characterize the global economic burden by analyzing the direct, indirect, and total costs associated with HD.

Methods

A comprehensive literature search was conducted across PubMed/MEDLINE, Web of Science, and Cochrane Library from inception to June 2024. The titles and abstracts were screened independently by two reviewers and full-text, English-language articles assessing direct, indirect, and/or total costs of HD were included. The costs were converted to annual costs in 2024 United States Dollars (USD).

Results

Out of the initial 608 de-duplicated articles, 19 full-text articles were included. The articles spanned 44 years, from 1980 to 2024. The studies covered a total of 15 countries. Annual costs in 2024 USD ranged significantly by region: Americas ($2542-$90,515), Europe ($40,000-$215,020), Asia ($1915-$7132), and Oceania ($3678-$8721). The highest costs were reported in Norway ($171,842) and the UK ($215,020), while Asian countries reported substantially lower costs (China: $6469; South Korea: $6305; Taiwan: $1915-$7132).

Conclusions

The global economic burden of HD varies substantially across regions, influenced by prevalence rates, healthcare systems, and reporting methodologies. Study limitations include heterogeneous cost reporting methods, potential underestimation in cost conversions, and lack of disease severity stratification. Standardizing cost-of-illness study methodologies and developing specific quality assessment tools would enhance cross-study comparability and improve resource allocation globally.

Keywords

Huntington's disease economic burden cost-of-illness healthcare costs direct costs

Introduction

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that significantly impacts families across generations, imposing substantial social and economic burdens on affected individuals and healthcare systems.¹ HD is a single-gene disorder resulting from an expanded CAG repeat on the Huntingtin (HTT) gene.² This leads to the production of the mutant Huntingtin (mHTT) protein, which abnormally folds and accumulates in the brain, causing neural atrophy.^3,4

HD manifests as a spectrum of progressive motor, cognitive, and psychiatric symptoms.⁵ Motor symptoms often include involuntary movements (e.g., chorea) and impaired voluntary movement, affecting coordination and function.⁵ Cognitive impairment in HD manifests as impairment in frontal-executive functions, attention, and psychomotor speed (ability to respond to change in the environment).⁶ Patients generally find it difficult to organize, multitask, and plan activities, with these symptoms eventually leading to dementia.⁷ Psychiatric symptoms vary widely and can include depression, anxiety, psychosis, irritability, and hallucinations, all of which substantially affect patients, caregivers, families, and the broader health system.^5,8,9

The global prevalence of HD underscores the disease's impact on healthcare. A recent meta-analysis estimated a pooled prevalence of 4.8 per 100,000 worldwide, with significantly higher prevalence rates reported in Europe and North America than in Asia and Africa.¹⁰ HD likely originated in Northwestern Europe and spread globally, potentially explaining lower prevalence rates in regions such as Taiwan, Japan, and Hong Kong.²

The economic burden of HD is significant and varies globally due to its genetic basis, diverse prevalence, and complex management requirements. Differences in prevalence and healthcare systems lead to varying economic impacts among countries. Additionally, the stigma associated with HD may result in underreporting, affecting prevalence estimates and potentially underestimating the economic burden. In addition, there may be differences in diagnostic criteria, though evidence suggests that this may not fully explain the differences in prevalence.¹¹ Different countries and populations may also have varying healthcare access levels, further complicating diagnosis and prevalence estimates.

Direct costs include healthcare and non-healthcare costs and consist of costs incurred by the health system, society, family, and individual patients.¹² Direct costs for HD include expenses related to hospitalization, drug treatment, and long-term care. Indirect costs generally refer to productivity loss due to morbidity and mortality, borne by the individual, family, society, or employer.¹² This may also include the cost of unpaid informal caregivers. Cost of illness studies, also referred to as the economic burden of disease studies, aim to recognize, identify, list, measure, and value the costs that a disease and its comorbidities can generate.¹²

A comprehensive understanding of HD's economic burden can inform policies and improve patient care strategies globally. This systematic review seeks to characterize the global economic burden of HD by analyzing direct, indirect, and total costs associated with the disease.

Methods

Search methods and sources

A protocol following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines was established and registered with PROSPERO (CRD42024552476). A comprehensive search strategy was developed and implemented across PubMed/MEDLINE, Web of Science, and the Cochrane Library from database inception to June 2024. The search strategy combined MeSH terms and keywords related to HD (e.g., “Huntington's Disease”, “Huntington's Chorea”) with economic terms (e.g., “costs”, “economic burden”, “healthcare utilization”). The complete search strategy for PubMed/MEDLINE was:

((Huntington's Disease[MeSH] OR Huntington's Chorea OR Huntington Disease) AND (costs[MeSH] OR cost OR economic* OR burden OR resource utilization OR healthcare utilization)).

Similar strategies were adapted for other databases. The detailed search strategy is available in Supplemental Table 1. The search was supplemented by hand-searching reference lists of included studies and relevant reviews. Grey literature was not included due to challenges in assessing methodological quality. Only full-text articles in English were considered.

Selection criteria

Studies reporting direct, indirect, or total costs associated with the treatment of HD were included, even if only one cost type was available. After de-duplication using EndNote, two reviewers independently screened titles and abstracts for inclusion. Discrepancies were resolved by consensus. Full-text articles meeting inclusion criteria were retrieved and screened, with data extraction completed in MS Excel.

Data extraction

A structured data extraction form was developed to capture key information from each study, including the author, publication year, study design, location, study period, database source (if applicable), data collection method, sample size, inclusion and exclusion criteria, diagnostic criteria for HD, patient characteristics, and cost details (direct, indirect, and total). Data extraction was conducted by Pooja Gokhale (PG), with accuracy verification performed by Lorenzo Villa Zapata (LVZ). Any discrepancies were resolved through discussion.

Conversion of cost values

The studies included in this review reported costs across different years, with some presenting costs in non-United States Dollar (USD) currencies. To ensure consistency, all costs were converted to USD based on the average exchange rate for August of each respective year, sourced from xe.com, an online foreign exchange tool.¹³ August was chosen as the reference month to align with the most recent Medical Consumer Price Index (MCPI) data available as of August 2024. After converting the costs to USD, they were adjusted to 2024 values using the following formula:

F u t u r e v a l u e = P r e s e n t V a l u e x {[1 + \frac{M C P I}{100}]}^{t}

MCPI: Medical Consumer Price Index – 3.2 in August 2024.¹³ t: time in years.

Cost standardization method

This standardization approach, described by Turner et al. (2019),¹⁴ carries some limitations. Primarily, it may lead to underestimation of cost values. Turner et al. (2019)¹⁴ also suggest that if costs were initially reported in USD after conversion, they should ideally be reverted to the original currency for inflation adjustments, then reconverted to USD. However, differing inflation measures across countries pose a challenge, making direct comparisons difficult. By applying a uniform inflation factor (MCPI) to reported USD values, this review standardizes costs to 2024 USD, facilitating cross-study comparison. It is important to note that, due to the variability in the original reporting years and countries, the standardized 2024 values are for comparative purposes only and may not represent actual costs. These values should be considered within the context of the original reporting parameters, including year, country, and possible differences in healthcare infrastructure, price regulations, and economic conditions.

Quality assessment

The methodological quality of the included studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Economic Evaluations.¹⁵ This checklist, developed by the JBI, evaluates the extent to which a study has addressed potential biases in design, conduct, and analysis. Although the JBI checklist is designed for cost-minimization, cost-benefit, cost-effectiveness, and cost-utility analyses, we adapted it to assess the quality of cost-of-illness studies, focusing specifically on cost elements.

In this adaptation, only costs were evaluated for questions related to the identification, measurement, credibility, and adjustment of costs and outcomes. Studies rated as “Unclear” on identifying all relevant costs were still included, acknowledging that decisions on cost inclusions can vary among researchers, with some costs potentially omitted for practical reasons. Sensitivity analyses were defined to include subgroup analyses or efforts to quantify or understand subgroup differences. Questions concerning alternative descriptions, clinical effectiveness, and incremental cost-consequence analyses were not applicable and thus were excluded.

Results

A total of 608 de-duplicated articles were screened by titles and abstracts, leading to the retrieval of 24 full-text articles for further review. Of these, two articles did not assess the cost of illness, three were conference abstracts, and one was a dissertation under embargo. An additional six articles were identified through hand-searching the citations of included studies, of which five were duplicates, and one was relevant. Thus, 19 articles were ultimately included in this review. The PRISMA flowchart for study selection is presented in Figure 1.

Figure 1.

PRISMA flowchart.

The included articles span 44 years, with publication dates ranging from 1980 to 2024. Table 1 provides detailed information on the selected studies, which represent 15 different countries. The United States had the highest representation with eight studies,^16–22 followed by the United Kingdom with three.^23–25 Other countries included Norway,²⁶ Israel,²⁷ Peru,²⁸ France,²⁴ Germany,²⁴ Italy,²⁴ Spain,²⁴ Canada,²⁹ South Korea,³⁰ China,³¹ Taiwan,³² South Africa,³³ and Australia.³⁴

Table 1.

Summary table of studies assessing economic burden of Huntington's disease.

Author	Country	Database/Source	Study design	Data collection method	Study duration	Inclusion criteria	Exclusion criteria	Huntington's diagnosis	Sample Size	Patient characteristics		Comorbidities
										Age (mean (SD))	Gender (Female (%))
Murman et al., 2002 ¹⁶	United States	Michigan Alzheimer's Disease Research Center registry	Cross-sectional	Survey	1993 to 1996	All living subjects with degenerative dementia diagnosis	NA	Neurologic exam, mental status, CT/MRI, family history, chorea	51	54.0 (1.0)	56.9	0.9 at diagnosis completion
Silva-Paredes et al., 2019 ²⁸	Peru	Neurogenetics Research Center at the Instituto Nacional de Ciencias Neurológicas (NRC-INCN)	Cross-sectional	Standardized questionnaire with interviews	NA	Adults with molecular HD diagnosis, regular follow-ups for ≥6 months, signed consent	NA	NA	97	48.7 (13.6)	63.9	NA
van Walsem et al., 2022 ²⁶	Norway	Oslo University Hospital and HD rehabilitation centers	Cross-sectional	Survey interviews	January to August 2014	Clinical HD diagnosis, residing in South-Eastern Norway	Incomplete data, criteria not met	Clinical HD diagnosis	86	57 (11.4)	45	43% reported ≥1 comorbidity
Barer et al., 2023 ²⁷	Israel	Maccabi Health Services (MHS) Database	Retrospective case-control	Database extraction	2000 to 2018	HD diagnosis (ICD-9-CM code 333.4), ≥18 years, ≥12 months MHS enrollment	<18 years, <12 months MHS enrollment	Neurologist, discharge report, medication pre-authorization, or ≥2 HD diagnoses	81	49.3 (13.6) -	57.5	Chronic disease registries used for comorbidities; specific data unavailable
Jones et al., 2016 ²³	United Kingdom	European Huntington's Disease Network (EHDN) REGISTRY database	Retrospective cohort	Database extraction	January to December 2013	UK patients in EHDN registry.	NA	NA	131	50	54.9	NA
Rodríguez-Santana et al., 2023 ²⁴	US, France, Germany, Italy, Spain, UK	Routine clinical consultations	Retrospective cross-sectional	Three questionnaires (eCRF, PPIE-P, PPIE-C)	September 2020 to May 2021	Adults (≥18) with manifest HD diagnosis ≥12 months prior to consultation	Clinical trial participants in the past 12 months	Clinical diagnosis	2094	47.3 (13.7)	40	NA
Peacock &. Harris, 1989 ²⁵	United Kingdom	North Western Regional Genetic Register	NA	NA	January 1984 to June 1987	NA	NA	NA	158	At home: 48.9, Residential care: 55.3	NA	NA
To et al., 2022 ¹⁷	United States	IBM MarketScan databases (Commercial, Medicare Supplemental, Multi-State Medicaid)	Retrospective cohort	Data extracted from database.	2009 to 2018	HD claim diagnosis (ICD-9-CM 333.4 or ICD-10-CM G10), ≥12 months pre-index and ≥3 months post-index	NA	NA	2473	NA	56.2	Charleston Comorbidity Score: 0.95
Divino et al., 2013 ¹⁸	United States	MarketScan Medicaid and Commercial Databases	Retrospective cohort	Database extraction	2002 to 2009	HD claim with ICD-9-CM diagnosis code 333.4, ≥180 days pre-index for early-stage patients, ≥6 months post-index	NA	NA	1272	48.5 (13.3)	54.1	Anxiety: 21%, Depression: 37.4%, Diabetes: 11.7%, etc.
Exuzides et al., 2021¹⁹	United States	Medicare FFS Research Identifiable Files (RIFs)	Retrospective Cohort	Database extraction	2013 to 2017	Medicare beneficiaries with HD diagnosis (ICD-9/10-CM code), continuous enrollment in Parts A/B and D	Managed Care beneficiaries	NA	3688	67.8 (12.4)	53.6	Charleston Comorbidity Index: 2.0
Exuzides et al., 2022²⁰	United States	IBM MarketScan databases (Commercial, Medicare Supplemental, Multi-State Medicaid)	Retrospective cohort	Database extraction	2009 to 2018	HD claim (ICD-9-CM 333.4 or ICD-10-CM G10), ≥12 months pre-index, ≥3 months post-index	Insurance plan switchers	NA	2669	54.6 (16.6)	56.1	Charleston Comorbidity Score: 1.16
Patel et al., 2023²¹	United States	Medicaid Analytic eXtract (MAX) files from 17 states	Retrospective cohort	Database extraction	2010 to 2014	HD diagnosis (ICD-9-CM 333.4), continuous FFS enrollment 1 year pre- and post-index	Dual eligibility.	NA	1785	46.8 (14.4)	63.7	NA
Shaw et al., 2022²⁹	Canada	Practitioner Claims, Discharge Abstract Database, National Ambulatory Care Reporting System	Retrospective cohort	Database extraction	April 2010 to March 2020	Two ICD-9/ICD-10-CA codes within 2 years in Discharge/National Ambulatory Systems	Juvenile HD (<21 years old)	NA	395	53.9 (13.8)	53.7	NA
To et al., 2023²²	United States	IBM MarketScan Commercial and Medicare Supplemental Databases	Retrospective cohort	Database extraction	2008 to 2018	Newly diagnosed HD, ≥21 years, no HD claims 12 months pre-index	Juvenile-onset HD (<21 years)	NA	1836	Median (IQR): LoHD: 70 (63–77), AoHD: 50 (42–55)	LoHD: 56.5, AoHD: 55.1	Charleston Comorbidity Score: LoHD: 1.5, AoHD: 0.6
Lee et al., 2023³⁰	South Korea	Health Insurance and Review Assessment Service (HIRA)	Retrospective cohort	Database extraction	2010 to 2019	Newly diagnosed HD patients (ICD-10 G10, RID registration)	NA	NA	152	Peak age range: 50–59	NA	Dementia: 37.5%, Dyslipidemia: 47.5%, Hypertension: 45.3%, etc.
Chen et al., 2024³¹	China	Rare Disease Patient Organisations (RDPOs) and other institutions	Cross-sectional survey	Data collection in a referenced Chinese paper	August to December 2019	RDPO-registered members with genetic confirmation for HD	NA	Genetic testing	269	48.93 (12.92)	57.6	NA
Chen & Lai, 2010³²	Taiwan	National Health Insurance Research Database (NHIRD)	Retrospective cohort	Data extraction	2000–2007	ICD-9-CM code 333.4	NA	NA	182	Peak age: Men (40–49), Women (50–59)	55.5	NA
Hayden et al., 1980³³	South Africa	National survey	Cross-sectional	Survey	NA	NA	NA	NA	NA	NA	NA	NA
McCabe and O'Connor, 2009³⁴	Australia	National MS and HD Associations	Prospective cohort	Mailed questionnaires	Baseline + 1-year follow-up	Diagnosis of HD	HD diagnosis	NA	26	59.2 (9.6)	30.8	NA

More than half of the studies (n = 10)^{17–23,29,30,32} employed a retrospective cohort study design. The remainder were cross-sectional (n = 6),^{16,24,26,28,31,33} case-control²⁷ or prospective cohort studies.³⁴ One study did not specify its design.²⁵ The sample size varied widely, ranging from 51 to 3688 participants. Less than half of the studies (n = 9)^{16–20,22,26,27,30} accounted for comorbidities.

Table 2 presents the methods of cost calculation and reported costs. Approximately 75% of the studies (n = 14)^{16,18,19,21–24,27–32,34} reported annual costs, while about 10% (n = 2)^17,20 reported costs per patient per month. One study provided six-month costs²⁶ and another reported weekly costs.²⁵ An additional study presented lifetime direct costs to society.³³

Table 2.

Summary of cost collection method and cost values.

Author	Method of cost calculation	Direct costs	Indirect costs	Total costs
Murman et al., 2002 ¹⁶	Calculated utilization for each type of care, multiplied by standard unit costs from Medicare and Medicaid.	Annual (1993): Hospital care: $1,600, Home healthcare: $2,500, Long-term care: $5000	NA	Annual (1993): $9000
Silva-Paredes et al., 2019 ²⁸	Prevalence approach with bottom-up costing; indirect costs via the human capital method.	Annual (2015): Drugs: $389, Ancillary services: $44, Specialist visits: $76, Primary care: $9, Inpatient care: $2, Medical devices: $70, Informal caregivers: $6,161, Transportation: $200	Annual (2015): $1170 Costs associated with temporary or permanent changes in work capacity/status for an HD patient as a result of his/her disease burden.	Annual (2015): $8121
van Walsem et al., 2022 ²⁶	6-month costs from Client Services Receipt Inventory (CSRI), unit costs from 2019 reimbursement fees; production loss via salary comparison.	6-month: Primary care: €1,227, Home care: €1,796, Nursing homes: €9,592, Rehabilitation: €2,848, Secondary care: €239, Specialists: €190, Hospital: €2,255, Out-of-pocket: €83, Informal care: €30,605	6-month: Social services: €1, Production loss: €18,907 Costs related to production loss were calculated as the difference between the six-month salary of a patient with HD and that of the general population in the same age group, adjusted for the proportion in part-time positions.	6-month: €66,789
Barer et al., 2023 ²⁷	Costs include hospitalizations, ER visits, outpatient visits, medications.	Annual (2018): Outpatient visits: $1,851, Inpatient visits: $11,780, Medication: $2053	NA	Annual (2018): $7343
Jones et al., 2016 ²³	National unit costs applied to service use; informal care estimated at replacement rate.	Annual (2013): Primary care: £2680.24, Hospital care: £2436.76, Diagnostics: £19.96, Medication: £851.42, Informal care: £14,085.24, Aids: £1531.46	NA	Annual (2013): £21,605.08
Rodríguez-Santana et al., 2023 ²⁴	Country-specific unit costs; indirect costs from productivity impact.	Annual (2020): Medical costs: €12,663, Non-medical: €2984	Annual (2020): €47,576 Indirect costs assessed the impact of HD on patient and caregiver work productivity based on hours worked per week, absenteeism, informal care costs, and early retirement.	Annual (2020): €62,372
Peacock & Harris, 1989 ²⁵	NA	Weekly (1984–1987): Residential: £148–£280, Accommodation/day center: £178, Home care: £146.9 (moderate), £114.55 (severe)	NA	NA
To et al., 2022 ¹⁷	Costs per patient per month (PPPM) to account for follow-up differences.	PPPM (2018): Outpatient: $945, Inpatient: $615, Pharmacy: $700, HD pharmacy: $452, Long-term care: $187, SNF: $160	NA	PPPM (2018): $2260
Divino et al., 2013 ¹⁸	Costs by type (inpatient, outpatient, pharmacy), adjusted to 2011 using CPI.	Annual (2011): Inpatient: $0–$29,701, Outpatient: $627–$29,572, ER: $0–$1,145, Pharmacy: $213–$6363	NA	Annual (2011): $1688–$39,028
Exuzides et al., 2021 ¹⁹	Costs for inpatient, outpatient, pharmacy, adjusted to 2017 USD.	Annual (2017): Outpatient: $10,213, Inpatient: $12,235, Pharmacy: $19,182	NA	Annual (2017): $41,631
Exuzides et al., 2022 ²⁰	Costs per patient per month, adjusted to 2018.	PPPM (2018): Outpatient: $1,288, Inpatient: $816, Pharmacy: $785, HD pharmacy: $506, Long-term care: $240, SNF: $209	NA	PPPM (2018): $2890
Patel et al., 2023 ²¹	Inpatient, outpatient, pharmacy, adjusted to 2014 USD.	Annual (2014): HD-related: Outpatient: $4422–$9,068, Inpatient: $616–$51,005, Pharmacy: $4932–$11,024. All-cause: Outpatient: $10,890–$36,420, Inpatient: $3791–$68,860, Pharmacy: $7383–$15,500	NA	Annual (2014): HD: $9970–$66,070, All-cause: $22,797–$95,251
Shaw et al., 2022 ²⁹	Per person-year follow-up, adjusted to 2020 CAD.	Annual (2020): HD-related: CA$16,755, HD-specific: CA$12,960	NA	Annual (2020): CA$23,211
To et al., 2023 ²²	Costs over 12 months post-index, adjusted to 2020 USD.	Annual (2020): Outpatient: $12,143–$13,657, Inpatient: $6071–$7,151, Hospitalizations: $5948–$6,497, ER: $882–$1,193, Pharmacy: $7835–$9694	NA	Annual (2020): $29,055–$31,701
Lee et al., 2023 ³⁰	Annual medical expenditure tracked per age group.	NA	NA	Annual (2019): KRW 6,569,341
Chen et al., 2024 ³¹	Bottom-up methodology; includes direct, non-medical, and indirect costs.	Annual (2019): Medical: €3265.65, Non-medical: €805.82	Annual (2019): €801.97 Indirect costs denoted the income deducted from the patient or accompanying individuals due to time spent on seeking medical treatment.	NA
Chen & Lai, 2010 ³²	NA	Annual: Outpatient: TWD 1944–2,900, Inpatient: TWD 51,342–184,557	NA	Annual: TWD 40,591–104,694
Hayden et al., 1980 ³³	Lifetime societal perspective, excluding economic productivity loss.	Direct lifetime cost: R23,000	NA	NA
McCabe & O’Connor, 2009 ³⁴	Summed costs from health insurance, medication, GP/specialist visits, hospitalization, etc.	NA	NA	Annual (2009): AUD 2800.98–6641.52

Table 3 summarizes the types of costs considered across studies. There was significant variability in the types of costs considered and the methods of reporting. Most studies included primary care visits (n = 17)^{17–24,26–34} and hospitalization costs (n = 17).^{16,17,19–24,26–34} Many also accounted for pharmacy/drug costs (n = 14),^{17–24,27–29,31,33,34} specialist visits (n = 14),^{17–22,24,26–29,31,33,34} long-term or nursing care (n = 12),^{16–22,24,25,29,30,33} ancillary/diagnostic costs (n = 10)^{17–20,23,24,26,28,29,31} and ER visits (n = 9).^{17–22,27,29,31} Less than half considered rehabilitation services (n = 8),^{17,18,20,22,26,27,31,34} and medical devices (n = 8).^{19,21–24,28,31,34} Very few studies examined home care (n = 5),^{16,21,25,26,34} transport costs (n = 4),^24,28,31,34 informal caregivers (n = 3),^23,26,28 out-of-pocket costs (n = 1),²⁶ and indirect costs (n = 4).^24,26,28,31 The variability in the types of costs considered may limit the comparability of costs across studies. Studies that considered multiple sources of direct costs may have higher estimates compared to those that did not consider certain costs, and thus comparison of the cost from different studies may be difficult.

Table 3.

Types of costs considered in each study.

	Direct costs													Indirect costs
Author	Primary	Specialists	Rehab	Home	Long-term/ nursing	Inpatient/ hospital	Pharmacy	Medical devices	Informal caregivers	Transport	Out of pocket	Ancillary/ diagnostic	ER	Costs due to changes productivity loss, or informal caregiving
Murman et al., 2002 ¹⁶	–	–	–	✓	✓	✓	–	–	–	–	–	–	–	–
Silva-Paredes et al., 2019 ²⁸	✓	✓	–	–	–	✓	✓	✓	✓	✓	✓	✓	–	✓
van Walsem et al., 2022 ²⁶	✓	✓	✓	✓	–	✓	–	–	✓	–	✓	✓	–	✓
Barer et al., 2023 ²⁷	✓	✓	✓	–	–	✓	✓	–	–	–	–	–	✓	–
Jones et al., 2016 ²³	✓	–	–	–	–	✓	✓	✓	✓	–	–	✓	–	–
Rodríguez-Santana et al., 2023 ²⁴	✓	✓	–	–	✓	✓	✓	✓	–	✓	–	✓	–	✓
Peacock &. Harris, 1989 ²⁵	–	–	–	✓	✓	–	–	–	–	–	–	–	–	–
To et al., 2022 ¹⁷	✓	✓	✓	–	✓	✓	✓	–	–	–	–	✓	✓	–
Divino et al., 2013 ¹⁸	✓	✓	✓	–	✓	–	✓	–	–	–	–	✓	✓	–
Exuzides et al., 2021 ¹⁹	✓	✓	–	–	✓	✓	✓	✓	–	–	–	✓	✓	–
Exuzides et al., 2022 ²⁰	✓	✓	✓	–	✓	✓	✓	–	–	–	–	✓	✓	–
Patel et al., 2023 ²¹	✓	✓	–	✓	✓	✓	✓	✓	–	–	–	–	✓	–
Shaw et al., 2022 ²⁹	✓	✓	–	–	✓	✓	✓	–	–	–	–	✓	✓	–
To et al., 2023 ²²	✓	✓	✓	–	✓	✓	✓	✓	–	–	–	–	✓	–
Lee et al., 2023 ³⁰	✓	–	–	–	✓	✓	–	–	–	–	–	–	–	–
Chen et al., 2024 ³¹	✓	✓	✓	–	–	✓	✓	✓	–	✓	–	✓	✓	✓
Chen & Lai, 2010 ³²	✓	–	–	–	–	✓	–	–	–	–	–	–	–	–
Hayden et al., 1980 ³³	✓	✓	–	–	✓	✓	✓	–	–	–	–	–	–	–
McCabe and O’Connor, 2009 ³⁴	✓	✓	✓	✓	–	✓	✓	✓	–	✓	–	–	–	–

✓: Indicates that this cost was considered; –: Indicates that this cost was not considered.

Table 4 provides the annual costs in 2024 USD. South Africa was excluded from cost reporting due to unavailable annual data. For the remaining 18 studies, the lowest costs were reported in Asian countries (South Korea, China, and Taiwan). Israel, Peru, and Australia also reported relatively lower costs, while the United States, Canada, and European countries showed higher annual costs, ranging from $20,000 to over $150,000. Figure 2 illustrates these costs in a color-coded map for 2024 USD.

Figure 2.

Map with annual costs in 2024 USD.

Table 4.

Annual USD costs in 2024 by country (calculated)^a.

Year of report	Conversion Factor	Annual costs in USD	MCPI in August 2024	Adjusted Annual Cost in 2024 (USD)	Country(ies)
1993	NA	$9000	3.2	$23,895.34	United States
2015	NA	$8121		$10,782.68	Peru
2019	1 € = 1.099 $	$146,802.22		$171,842.71	Norway
2018	NA	$7343		$10,383.65	Israel
2013	1 £ = 1.549 $	$33,466.27		$40,428.30	United Kingdom
2020	1 € = 1.195 $	$74,534		$84,542.14	United States, France, Germany, Italy Spain, and United Kingdom
1984–1987	1984: 1 £ = 1.3098 $ 1987: 1 £ = 1.6305 $	$40,010.46–$60,998.63		$128,312.07–$215,020.17	United Kingdom
2018	NA	$27,120		$32,761.81	United States
2011	NA	$1688–$39,028		$2542–$58,776	United States
2017	NA	$41,631		$51,900.88	United States
2018	NA	$34,680		$41,894.53	United States
2014	NA	$9970–$66,070		$13,658.9–$90,515.9	United States
2020	1 CA$ = 0.767 $	$17,802.84		$20,193.34	Canada
2020	NA	$29,055–$31,701		$32,948.37–$35,948.94	United States
2019	1 KRW = 0.00082	$5386.86		$6305.71	South Korea
2019	1 € = 1.099 $	$5355.43		$6469.52	China
2000–2007	2000: 1 TWD = 0.032 $ 2007: 1 TWD = 0.030	$1121.773–$3350.208		$1915.98–$7132.59	Taiwan
1979	1 R = 0.8348 $	NA		NA	South Africa
2009	1 AUD = 0.8434 USD	$2362.34–$5601.48		$3678.16–$8721.50	Australia

All costs were converted to USD based on the average exchange rate for August of each respective year, and then adjusted to 2024 values using the following formula: $F u t u r e v a l u e = P r e s e n t V a l u e x {[1 + \frac{M C P I}{100}]}^{t}$ .

MCPI: Medical Consumer Price Index – 3.2 in August 2024; t: time in years.

Supplemental Table 2 presents the quality assessment of the included studies. All 19 studies had well-defined research questions. The majority (n = 15) included all relevant costs and measured them accurately. Only two studies conducted subgroup adjustments. Three studies received an “Unclear” rating for generalizability, as they discussed transferability but lacked sufficient methodological description. These studies were included despite the “Unclear” rating, as the objective of this review was to describe cost estimates across studies.

Discussion

Our systematic review found that the global economic burden of HD varies widely, ranging from $1915.98 to $215,020.71 annually. These costs represent a mix of out-of-pocket costs and those covered by insurance. Out-of-pocket costs have been specifically considered in only one study.²⁶ For countries with a national insurance system, such as China, South Korea, Taiwan, Israel, the United Kingdom, Norway, and others, the costs can generally be assumed to be covered by insurance, though this has not been specified. A mix of insurance coverage and out-of-pocket costs may be assumed for countries such as Canada, Australia, and the United States.

Substantial differences in economic burden were observed across countries, with Asian countries generally reporting lower costs. For example, China and South Korea reported annual costs of around $6,000, while Taiwan's costs ranged from approximately $2000 to $7000.^30–32 These lower costs may reflect the lower prevalence of HD in Asian populations (0.1–0.4 per 100,000), compared to higher rates in Caucasian populations (5–10 per 100,000).³⁵

Several factors could explain this lower prevalence in Asia. Research suggests that average CAG repeat sizes are larger in Western populations than in Asian populations.³⁵ Additionally, East Asian populations predominantly carry the C haplotype, while most HD patients in Europe have the A haplotype, which is associated with a higher risk of HD.³⁵ Limited access to genetic testing, differences in diagnostic procedures, and stigma surrounding HD may also contribute to lower prevalence estimates.³⁶

China's national medical security system, with the Employee Basic Medical Insurance (EBMI) and Residents Basic Medical Insurance (RBMI) programs, provides extensive health coverage.³⁷ Recent data indicates that approximately 97% of China's population is insured, with the National Centralized Drug Procurement (NCDP) program regulating drug prices.^38–40 The lower prevalence, high level of insurance coverage, and lower drug prices may explain the lower HD-related costs in China.

Taiwan and South Korea also have national health insurance systems.^41,42 In these countries, lower HD prevalence, combined with nationalized healthcare, likely contributes to reduced economic burdens. However, the studies from South Korea and Taiwan did not consider several cost components, such as specialist visits, home care, rehabilitation, medications, informal caregivers, and indirect costs. This limited scope could further explain the lower reported costs. Additionally, the Taiwan study, conducted from 2000–2007, may reflect outdated cost values due to conversion and inflation adjustments.

There is also evidence that HD may have an atypical manifestation in Asian populations,³⁵ possibly leading to a higher rate of missed diagnoses. This may lead to a lower economic burden on the healthcare system, since patients may not receive the required care. In addition, studies indicate that uptake of genetic testing in Asian countries may be lower, due to cost concerns, as well as lack of awareness.^43,44 This may also contribute to a lower rate of diagnosis, and thus a lower economic burden.

In Latin America, Peru reported HD costs of around $10,000.²⁸ HD prevalence in Latin America (0.5–4/100,000) is lower than in the US (4–7 per 100,000), though underdiagnosis may be a factor.⁴⁵ Genetic testing in Peru is not widely available and has many limitations,⁴⁶ potentially leading to underdiagnosis as well as impacting the economic burden. Peru's healthcare system is fragmented, with services concentrated in urban areas, potentially impacting cost estimates. Exclusions of rehabilitation, home care, nursing facility costs, and reliance on standardized questionnaires may have introduced bias, leading to lower cost estimates.⁴⁷

Similarly, Israel reported costs of around $10,000.²⁷ The HD prevalence in Israel is 4.36 per 100,000, at the lower end of rates in Europe and the US.⁴⁸ Israel's national health insurance system, with universal coverage funded through health taxes,⁴⁹ likely reduces costs. Exclusions of costs for home care, nursing facilities, informal caregivers, and diagnostic services may contribute to lower estimates.

Australia reported costs between $3000 and $9,000, despite having a higher HD prevalence comparable to Europe and North America.⁵⁰ Australia's hybrid healthcare system, combining public and private insurance options, may help manage costs effectively. However, the study did not include costs for nursing facilities, informal caregivers, or diagnostic services, which may account for the relatively low estimates. In addition, the data in this study was self-reported and thus may not accurately represent the economic burden of HD.

In contrast, European countries reported higher annual costs, ranging from $40,000 to $215,000. The highest cost was reported in a 1989 UK study that presented weekly costs extrapolated to annual costs in 2024 USD.²⁵ The conversion process, as well as higher HD prevalence in Europe, may explain these elevated costs. Another UK study reported annual costs of approximately $40,000,²³ and a global burden of disease study conducted in the US and multiple European countries reported yearly costs of around $85,000.²⁴ The indirect costs in this study assessed the impact of HD on patient and caregiver work productivity based on hours worked per week, absenteeism, informal care costs, and early retirement and likely contributed to the higher estimates.

A study from Norway reported costs of around $170,000 annually.²⁶ This study, which had a small sample size and relied on self-reported survey data, included productivity losses accounting for over 25% of total costs. The absence of database verification and reliance on conversion calculations may have contributed to the higher cost estimate.

In North America, HD-related costs in the United States ranged from $2542 to $90,515, with most studies reporting between $20,000 and $40,000.^16–22,24 Variations in cost estimates may reflect differences in cost inclusions, as none of the studies considered informal caregiving or out-of-pocket expenses, and only one study included indirect costs.²⁴ The US healthcare system, one of the most expensive globally, combined with higher HD prevalence, likely accounts for the higher cost range.⁵¹

Canada reported costs of around $20,000,²⁹ at the lower end of the US range. Canada's publicly funded healthcare system, with 70% of expenditures covered by taxes,⁵² may help contain costs. Exclusions of home care, medical devices, and informal caregiving expenses may contribute to lower reported costs, despite comparable HD prevalence.

The results from this review are similar to those reported by Patil et al. (2024).⁵³ While this study provided valuable insights regarding the cost variations in HD by stage, our review complements these findings by addressing geographic and systemic influences on HD's economic impact, offering a global lens that highlights regional disparities in healthcare systems, prevalence rates, and economic burden.

Overall, HD costs are generally higher in North America and Europe than in Asia, likely due to higher disease prevalence and healthcare system demands. Variability in reported costs also reflects differences in cost components considered across studies. Only four studies explicitly stated their analytical perspective, highlighting a need for standardized approaches in cost-of-illness research. Establishing comprehensive guidelines for cost components and developing a dedicated quality assessment tool for these studies is essential.

This review has a few limitations. Studies with limited methodological clarity were included for comprehensiveness, which may restrict comparability. The studies included in this review employ various methodologies for cost calculations, which presents a significant challenge in making direct comparisons. The differences in the types of costs included, the costing method, the units of reporting (e.g., per patient per month, or annual), the year of the report, and the country, must be considered while assessing the results. Additionally, converting costs to 2024 USD, especially for older studies, may introduce inaccuracies. Finally, this review does not stratify costs by disease stage or severity, which could enhance cross-study comparisons.

Conclusion

HD imposes a substantial and variable economic burden worldwide, with disparities driven by prevalence, healthcare systems, and cultural factors. Cross-country comparisons are challenging, underscoring the need for more rigorous and standardized methodologies in cost-of-illness studies. Developing guidelines for consistent methodologies and a quality assessment tool would help to accurately assess HD's global economic impact, guiding policy and resource allocation to improve patient care globally.

Supplemental Material

sj-docx-1-hun-10.1177_18796397251319209 - Supplemental material for Economic burden of Huntington’s disease: A systematic review

Supplemental material, sj-docx-1-hun-10.1177_18796397251319209 for Economic burden of Huntington’s disease: A systematic review by Pooja Gokhale and Lorenzo Villa Zapata in Journal of Huntington's Disease

Footnotes

Acknowledgments

The authors have no acknowledgments to report.

ORCID iD

Pooja Gokhale

Lorenzo Villa Zapata

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability

The data for this study may be made available by the corresponding author upon request.

Supplemental material

Supplemental material for this article is available online.

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