21st June 2023

Huntington’s Disease

Pathophysiology

Huntington’s disease (HD) is an autosomal dominant neurodegenerative condition. It is caused by a CAG trinucleotide repeat mutation of the HTT gene, which encodes the protein huntingtin. Huntingtin is important in neuronal function. The CAG segment repeats an abnormal number of times – 36-120 times. It takes 40 CAG repeats for HD symptoms to develop. CAG repeats accumulate, causing symptoms to present earlier and more severely in subsequent generations, a phenomenon known as anticipation.

Presentation and diagnosis

Patients with HD usually start to have symptoms at 35-44 years old. The majority of patients have a family history.

HD presents in stages, which are:

• Early stage:
  • Irritability
  • Apathy
  • Depression
  • Hallucinations
  • Abnormal eye movements
  • Anosmia
• Middle stage:
  • Dystonia
  • Chorea
  • Unsteady gait
  • Frailty
• Late stage:
  • Rigidity
  • Bradykinesia
  • Immobility
  • Aphasia
  • Dysphagia

MRI head shows atrophy of the caudate and later cerebellar and cortical atrophy. The definitive, gold standard way diagnostic test is genetic testing looking for CAG repeats.

Treatment

The treatment of HD is currently symptomatic.

For the chorea, the treatment can include:

• Tetrabenazine
• Amantadine
• Riluzole
• Benzodiazepines

For parkinsonism, the treatment is:

• Levodopa
• Amantadine

Physiotherapy and Botulinum toxin A injections can be useful for dystonia. For mood issues, consider starting SSRIs or TCAs.

There are currently further studies of promising treatments, such as gene silencing therapies.