OVERVIEW

What is Huntington's disease?

Huntington's disease (Huntington chorea), also known as Huntington's disease (HD), chronic progressive chorea, or hereditary chorea, is an autosomal dominant genetic disorder caused by genetic alterations on the short arm of chromosome 4, leading to degeneration of the basal ganglia and cerebral cortex. Clinically, it is characterized by insidious onset, slowly progressive choreiform movements, and progressive cognitive impairment, psychiatric abnormalities, and dementia. There is currently no cure, and treatment mainly focuses on symptomatic and supportive care.

Is Huntington's disease common?

The global prevalence of Huntington's disease is 2.7 per 100,000. It is more common in Caucasians and relatively rare in China. Recent studies show a prevalence of 0.4 per 100,000 in Asia, compared to 5.7 per 100,000 in Europe, North America, and Australia. The age of onset ranges from childhood to 70–79 years, with the majority of cases occurring in middle age (30–50 years).

Are Huntington's disease and Sydenham's chorea the same condition?

No, they have different pathogenic mechanisms.

Sydenham's chorea, often a manifestation of acute rheumatic fever, primarily affects children and adolescents aged 5–15. It typically begins with psychiatric abnormalities, followed by involuntary movements involving the face and limbs, and may be accompanied by speech and swallowing difficulties, as well as decreased muscle tone. Intelligence is generally unaffected, and some patients may exhibit other symptoms of rheumatic fever.

SYMPTOMS

What are the manifestations of Huntington's disease?

Huntington's disease has an insidious onset, progresses slowly, and shows no gender differences. Its clinical manifestations mainly include the following aspects:

• Movement disorders: Choreiform involuntary movements are the most typical manifestation of this disease, usually involving sudden, rapid, involuntary jerks or twitches in the face, limbs, or trunk, such as grimacing, nodding, or piano-playing-like finger movements. As the disease worsens, voluntary movements become significantly impaired, leading to clumsiness, rigidity, inability to perform complex voluntary activities, dysphagia, and dysarthria. In advanced stages, patients may become immobile, entering a stuporous state.

• Cognitive impairment: Progressive dementia is common. Early symptoms include declines in calculation and memory in daily life and work, followed by reduced comprehension and judgment, and even changes in personality, emotion, and cognition, affecting social interactions.

• Psychiatric disorders: Initial symptoms include changes in personality and behavior, such as anxiety, tension, irritability, excitability, untidiness, or antisocial behavior. Later, mood disorders like depression and apathy, as well as other psychiatric symptoms (e.g., hallucinations, mania), may develop. Mood disorders often precede movement disorders. Suicidal tendencies may also occur. Neurological and psychiatric symptoms progressively worsen, eventually leaving patients in a demented and mute state.

• Eye movement abnormalities: Abnormal eye movements can be a prominent feature in Huntington's disease patients, particularly in younger adults. A characteristic finding is the loss of saccadic eye movements while smooth pursuit movements remain intact.

• Weight loss and cachexia: Despite efforts to maintain adequate caloric intake, weight loss and cachexia are common features of Huntington's disease. Contributing factors may include increased energy expenditure due to hyperkinesia and altered cellular metabolism in muscle or adipose tissue.

• Other symptoms: Some patients may develop cerebellar limb and gait ataxia, myoclonus, seizures, or generalized dystonia.

What conditions should Huntington's disease be differentiated from?

Huntington's disease needs to be distinguished from benign familial chorea, Sydenham's chorea, neuroacanthocytosis, and drug-induced tardive dyskinesia. Additionally, systemic diseases such as hyperthyroidism, systemic lupus erythematosus, and polycythemia vera may also present with choreiform movements and require differentiation.

CAUSES

What is the cause of Huntington's disease?

The primary cause of Huntington's disease is an abnormality in the IT15 gene located at 4p16.3 on chromosome 4. The abnormal increase in the copy number of the trinucleotide (CAG) repeat sequence within the coding region of this gene leads to mutations in the encoded Htt protein, making it difficult to maintain its various cellular functions and resulting in corresponding functional impairments.

DIAGNOSIS

How is Huntington's disease diagnosed?

Doctors can generally diagnose it based on a positive family history, typical choreiform movements, and psychiatric disorders accompanied by progressive dementia. Genetic testing can confirm the diagnosis.

What tests do Huntington's disease patients need? What are the findings of these tests?

• Genetic testing: Unstable abnormal expansion of CAG repeat sequences. A range of 36–39 may indicate the disease, while over 40 confirms the diagnosis. This method can be combined with clinical evaluation for diagnosis or used for prenatal genetic assessment. However, this test is expensive and not available in most hospitals.

• Lumbar puncture and cerebrospinal fluid (CSF) analysis: A thin needle is inserted into the lower back to collect a small amount of CSF. Reduced gamma-aminobutyric acid (GABA) levels may be detected.

• Head CT and MRI: Early stages often show no significant abnormalities. As the disease progresses, typical findings include bilateral caudate nucleus atrophy, causing outward bulging of the lateral ventricles' frontal horns (characteristic "butterfly sign"). Further progression may lead to varying degrees of cortical and subcortical atrophy.

• Single-photon emission computed tomography (SPECT): Reveals significantly reduced blood flow in the caudate nucleus and lentiform nucleus, as well as decreased flow in the frontal and parietal lobes.

• PET: Shows markedly reduced glucose metabolism in the caudate nucleus, which may precede caudate atrophy.

• Electroencephalogram (EEG): Displays low-amplitude fast waves, particularly in the frontal lobe, though this is nonspecific.

What should Huntington's disease patients pay attention to during a lumbar puncture?

Lumbar puncture is a common and relatively safe clinical procedure, so patients need not worry excessively.

• Before the procedure, relevant tests should be completed to assess the patient's suitability.

• Patients with suspected increased intracranial pressure must first undergo fundus examination. The procedure is contraindicated in cases of significant papilledema, signs of brain herniation, shock, severe debilitation, local skin infection, or posterior fossa space-occupying lesions.

• If no contraindications exist, cooperate with the doctor. The procedure typically takes about 10 minutes. The patient should assume a fetal position (knees to chest, back curved) and remain still throughout.

• After the procedure, lie flat without a pillow for 4–6 hours to prevent low intracranial pressure syndrome (caused by excessive CSF leakage from the puncture site). Otherwise, symptoms like headache, nausea, vomiting, or dizziness may occur.

• Keep the puncture site dry and avoid water contact for at least 24 hours.

• Report any discomfort to medical staff promptly.

TREATMENT

Which department should I visit for Huntington's disease?

Neurology.

Does Huntington's disease require hospitalization?

Hospitalization is not necessary in the early stages, but long-term outpatient follow-up is required. As the disease progresses and patients lose the ability to care for themselves, they often need caregivers. In the late stages, complications such as infections and malnutrition may require hospitalization.

Can patients with Huntington's disease have children?

Huntington's disease is an autosomal dominant genetic disorder, meaning there is a 50% chance the offspring will inherit the disease. Therefore, it is not recommended for affected individuals to have children.

How is Huntington's disease specifically treated?

Currently, there are no effective treatments to alter the progression of Huntington's disease, but measures can be taken to improve clinical symptoms, reduce chorea-like movements, and enhance the patient's quality of life.

Treatment for chorea symptoms:

• Dopamine receptor blockers: Haloperidol, chlorpromazine, or perphenazine may be used. Start with a low dose and gradually increase, while monitoring for extrapyramidal side effects such as tremors, shuffling gait, restlessness, or pacing.

• Central dopamine depleters: Tetrabenazine.

• Cholinergic drugs: Neostigmine, though its efficacy is uncertain.

For patients with depression, antidepressant treatment is given: Typically, tricyclic antidepressants (e.g., amitriptyline, doxepin) or selective serotonin reuptake inhibitors (e.g., paroxetine, sertraline) are used.

For patients with psychiatric symptoms, antipsychotic drugs are given: Such as olanzapine, risperidone, or tiapride, with doses adjusted based on patient response.

Treatment for late-stage complications: Guide proper eating to prevent aspiration pneumonia. If necessary, insert a gastric tube for liquid or semi-liquid feeding. Strengthen nursing care to prevent bedsores and infections.

What is the prognosis for Huntington's disease?

Currently, there is no effective treatment to control the progression of Huntington's disease. The condition progresses gradually, with a disease course lasting approximately 10–25 years (average 19 years). Early-onset cases (before age 20) progress more rapidly, while those with onset after age 50 progress relatively slower.

In the final stages, patients often suffer from malnutrition due to difficulty swallowing, become bedridden due to mobility impairment, and develop complications such as aspiration pneumonia, hypostatic pneumonia, or bedsores, ultimately leading to death.

DIET & LIFESTYLE

What should Huntington's disease patients pay attention to in their diet?

In the early stages, these patients do not need to pay special attention to their diet; a regular diet is sufficient. However, when swallowing difficulties occur in later stages, attention should be paid to eating speed and food texture to prevent choking.

What should Huntington's disease patients pay attention to in daily life?

Place padding on furniture and beds to prevent patients from falling and getting injured.

Does Huntington's disease require follow-up examinations? How are they conducted?

Yes, long-term follow-up with a neurologist is necessary. Doctors need to monitor disease progression, adjust medications, and observe any adverse drug reactions.

PREVENTION

Can Huntington's disease be prevented?

Huntington's disease is a genetic disorder. Individuals with a family history of this condition should undergo enhanced genetic screening before childbirth to reduce the likelihood of affected offspring.