Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a genetic mutation—an expanded CAG repeat in the HTT gene. This mutation produces an abnormal huntingtin protein, leading to the gradual loss of nerve cells. The basal ganglia, particularly the striatum, is affected early, impacting movement, mood, and cognitive functions. HD follows a predictable progression through distinct stages that guide management and care planning.
Early Stage Symptoms and Diagnosis
The initial presentation of HD is often subtle, easily mistaken for mood changes or other conditions. Behavioral changes frequently precede noticeable motor symptoms, sometimes by many years. Early psychiatric manifestations commonly include irritability, depression, apathy, and mood swings.
Minor coordination issues, such as clumsiness or difficulty with fine motor control, might also be present. Individuals may begin to struggle with complex tasks requiring organization or concentration, such as managing finances or driving. At this stage, a person is generally still fully functional and can maintain independent living and employment.
A diagnosis is typically made by a neurologist based on a thorough neurological exam, family history, and characteristic symptoms. Genetic testing confirms the diagnosis by detecting the expanded CAG repeat. The number of CAG repeats correlates with the age of onset, where a larger number predicts an earlier start to the disease.
Mid-Stage Progression and Functional Decline
As the disease moves into the mid-stage, symptoms become overtly debilitating and significantly impact daily life. The characteristic involuntary movements (chorea) become prominent, manifesting as uncoordinated, jerking motions that interfere with walking, speaking, and eating. Swallowing difficulties (dysphagia) often worsen, increasing the risk of aspiration.
Cognitive decline progresses to dementia, making problem-solving and decision-making much harder. Individuals typically lose the ability to work or drive and can no longer manage complex instrumental activities of daily living (IADLs). Persistent behavioral issues continue, and the person requires increasing assistance with basic activities of daily living (ADLs). Constant movement from chorea and dysphagia often leads to significant weight loss and poor nutritional status.
Late Stage: Severe Impairment and End-of-Life Care
The late stage is characterized by severe impairment, with the individual becoming fully dependent on others for all care needs. The chorea often lessens or stops entirely, replaced by rigidity, dystonia, and bradykinesia. The person is typically non-ambulatory, confined to a bed or wheelchair, and unable to speak clearly due to severe dysarthria or mutism.
While external communication is severely limited, many individuals appear to retain some level of comprehension. Care shifts entirely to comfort and palliation, focusing on managing complications like skin breakdown and preventing aspiration pneumonia, a frequent cause of death due to severe dysphagia. Ethical decisions surrounding end-of-life planning, such as the use of artificial feeding tubes, are addressed to ensure the patient’s wishes are respected.
Therapeutic Strategies Across the Stages
Treatment goals for Huntington’s disease are highly personalized and change depending on the stage of progression. In the early stage, the focus is on maintaining independence and managing psychiatric symptoms. Antidepressants or mood stabilizers may be prescribed to control depression, anxiety, and irritability.
As the disease progresses into the mid-stage, the primary goal shifts to controlling disruptive involuntary movements and supporting function. VMAT2 inhibitors, such as tetrabenazine or deutetrabenazine, suppress chorea by blocking neurotransmitter transport. Physical, occupational, and speech therapies help manage mobility, maintain independence in ADLs, and address swallowing difficulties; nutritional support, such as a G-tube, may be considered.
In the late stage, care becomes fully palliative, concentrating on maximizing comfort and quality of life. Pain management, including addressing muscle rigidity and contractures, is a primary concern. Palliative care teams provide comprehensive support, managing complex physical symptoms and offering emotional and spiritual assistance for the patient and the family.