What is Huntington's disease and how is it managed?

From the Guidelines

Huntington's disease is a fatal neurodegenerative disorder that requires a multidisciplinary approach for management, focusing on symptom control and supportive care, with genetic counseling being crucial for at-risk individuals. Huntington's disease is an inherited disorder caused by a genetic mutation in the HTT gene, leading to progressive brain cell death, typically appearing in mid-adulthood and causing movement disorders (chorea), cognitive decline, and psychiatric symptoms 1. The disease affects approximately 3-5 out of 100,000 individuals, with a higher prevalence in populations of western European origin 1.

Key Characteristics of Huntington's Disease

• Inherited neurodegenerative disorder
• Caused by a genetic mutation in the HTT gene
• Leads to progressive brain cell death
• Typically appears in mid-adulthood
• Causes movement disorders (chorea), cognitive decline, and psychiatric symptoms

Management of Huntington's Disease

• Focuses on symptom control and supportive care
• Medications like tetrabenazine, deutetrabenazine, or antipsychotics may help control chorea
• Psychiatric symptoms can be treated with antidepressants or mood stabilizers
• Cognitive decline may benefit from cognitive rehabilitation therapy
• A multidisciplinary approach is essential, including neurologists, psychiatrists, physical therapists, occupational therapists, speech therapists, nutritionists, and social workers

Importance of Genetic Counseling

• Genetic counseling is crucial for at-risk individuals
• Each child of an affected parent has a 50% chance of inheriting the disease
• Genetic testing to determine the CAG repeat number for each allele is commercially available and the diagnostic test of choice 1
• Regular follow-up appointments every 3-6 months help adjust treatment as the disease progresses.

From the FDA Drug Label

Huntington’s disease is a progressive disorder characterized by changes in mood, cognition, chorea, rigidity, and functional capacity over time. The diagnosis of HD was based on family history, neurological exam, and genetic testing Patients with Huntington’s disease are at increased risk for depression, suicidal ideation or behaviors (suicidality).

Huntington's Disease Management:

• The primary goal of management is to control symptoms, particularly chorea, which is a prominent feature of the disease.
• Tetrabenazine is a medication used to treat chorea associated with Huntington's disease.
• Management also involves monitoring for depression and suicidality, as these are common comorbidities.
• Regular assessments of the patient's condition, including mood, cognition, and functional capacity, are necessary to adjust treatment as needed.
• Genetic testing for CYP2D6 metabolizer status is recommended before prescribing high doses of tetrabenazine.
• Dose adjustments may be necessary based on the patient's metabolizer status to minimize the risk of adverse effects.
• Close monitoring for signs of Neuroleptic Malignant Syndrome (NMS), a potentially fatal condition, is essential when using tetrabenazine 2, 2, 2.

From the Research

Definition and Characteristics of Huntington's Disease

• Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by cognitive, motor, and psychiatric symptoms 3.
• It is an inherited disease caused by the amplification of a nucleic acids triplet repeat, leading to core symptoms of chorea, progressive dementia, and psychiatric manifestations such as depression, irritability, apathy, and psychosis 4.
• The disease is usually confirmed through identification of an increased CAG repeat length in the huntingtin gene in a patient with clinical features of the condition 5.

Management and Treatment of Huntington's Disease

• Current treatments for HD are symptomatic, and largely directed at the chorea and neurobehavioural problems, although supporting trial evidence for these is often limited 5.
• Tetrabenazine is the first US Food and Drug Administration (FDA)-approved treatment for chorea related to HD, and has shown clear efficacy for the control of chorea 4, 6.
• Other pharmacological interventions, such as anti-dopaminergic drugs, glutamate receptor antagonists, and energy metabolites, have revealed no clear effectiveness in controlling symptoms 4.
• Emerging pharmacological approaches, including the modulation of protein homeostasis, mitochondrial function, neuro-inflammation, and neurotransmitter systems, offer promising strategies to alleviate symptoms and slow down disease progression 3.

Diagnosis and Premotor Phase

• The diagnosis of HD is usually straightforward, but unusual presentations can occur, and it can be difficult to know when someone has transitioned from being an asymptomatic carrier into the disease state 5.
• There is increasing evidence that both cognitive and neuropsychiatric symptoms can, and often do, present decades before the onset of motor symptoms, in the premotor phase of the disease 7.
• Early symptoms of HD can be very debilitating and are often disregarded by doctors, but acknowledging them can lead to earlier diagnosis and treatment, improving the patient's independence and quality of life 7.