Huntington's disease (HD) is a rare yet destructive neurodegenerative disorder that leads to the progressive deterioration of nerve cells and results in a diverse range of symptoms. HD affects approximately 1 in every 10,000 individuals and currently there are 30,000 HD cases in the USA. This degenerative condition is characterized by the progressive development of psychiatric manifestations, cognitive decline, and uncontrolled jerky movements known as chorea or uncontrolled movements in the person’s fingers, feet, face, or torso [1, 2]. Typically, these symptoms manifest between the ages of 30 and 50 and persist for a prolonged duration, spanning approximately 17–25 years [3].

HD is an autosomal dominant disorder, meaning that every offspring of an affected parent has a 50% chance of inheriting the causative gene mutation. In addition to the adult-onset form of the disease, HD can also manifest in children and young adults [4]. Juvenile HD constitutes 5–10% of total HD cases and is characterized by a more rapid progression rate and a more severe clinical presentation than the adult-onset form of the disease [5].

HD is caused due to a DNA mutation in the Huntingtin (HTT) gene, characterized by the expansion of CAG repeats from the normal range of 20 repeats to over 40 repeats. This expansion leads to the production of an abnormal and elongated protein that accumulates in brain cells, leading to their damage and eventual death. The striatum, a brain region responsible for movement, mood, and memory, is particularly affected in HD. Consequently, HD symptoms can be broadly classified into three categories: motor, cognitive, and behavioral. Signs of HD can vary widely, but often involve symptoms such as personality changes, mood swings and depression, forgetfulness and impaired judgment, unsteady gait and involuntary movements (chorea), slurred speech, difficulty in swallowing, and significant weight loss [4, 6].

Individuals with Huntington’s disease are divided into early, middle, and late stages at baseline, using a modified algorithm. This algorithm was developed and validated by Divino et al. [3] through a literature review, data analysis, and expert input. Late-stage disease markers include the use of nursing home care, feeding tubes, incontinence, bedsores, hospice care, two or more falls in a month, and swallowing difficulties. Middle-stage markers include home assistance, physical therapy, dementia, gait disorder, dysarthria, speech therapy, or any falls. People with late-stage disease are first identified by the presence of late-stage markers, followed by those with middle-stage markers. Those without either late- or middle-stage markers are considered to be in the early stage of HD [3].

As of today, there is no cure available for this disease, however, symptoms can be managed using a range of medications and non-drug treatments. Current therapies prescribed for HD can be categorized by the symptoms they treat. These categories include chorea medication, antipsychotic medication, antidepressants, and mood-stabilizing medication, as well as non-drug therapies [7].

This disease has a significant impact on patients, caregivers, and the healthcare system, however, a limited number of studies quantify this impact across disease stage. There is a lack of comprehensive direct and indirect medical cost data for HD. This review particularly focuses on answering the following questions:

1.

What types of costs are frequently identified for individuals diagnosed with HD and how big is the impact?

2.

How do costs vary across the different stages of HD, and which costs have the most significant impact for each stage?

Conducting a systematic review to identify the costs associated with HD is crucial for health policy planners and decision-makers to better understand the resources needed to care for these patients, which is essential for prioritizing resource allocation, targeting specific medical and social issues, and evaluating the effectiveness of policies and interventions, especially given the rarity and high impact of HD.

Understanding the costs at different stages of HD is particularly important. In the early stages of HD, most treatments aim to manage symptoms and potentially slow disease progression, often resulting in higher treatment costs during this period. Understanding these costs is crucial because it highlights the importance of early intervention, which can improve quality of life and potentially delay the more severe stages of the disease. As HD progresses, it can impair a person’s ability to function independently and affect their capacity to work, ultimately leading to productivity losses. In the late stage, the burden shifts significantly as the patients often lose the ability to perform basic daily activities independently and require extensive caregiver support, which may result in higher caregiver costs. By analyzing these costs, we can emphasize the need for policies that support caregivers and provide adequate resources for late-stage care. These insights are vital for developing targeted policies that address the needs and resource requirements at each stage of HD, ultimately aiming to improve patient outcomes and optimize healthcare expenditures.