Huntington Disease

Question 1

What is huntington disease?

Answer 1

Huntington’s is a cause of chorea and is a neurodegenerative disorder characterised by the LACK of the inhibitory neurotransmitter GABA.

Question 2

What is Chorea?

Answer 2

A continuous flow of jerky, semi-purposeful movements, flitting from one part of the body to another.
They may interfere with voluntary movements but cease during sleep.

Question 3

What type of condition is Huntington disease?

Answer 3

Autosomal dominant

Question 4

What sequence is repeated in Huntington disease?

Answer 4

CAG

Question 5

What does repetition of the CAG sequence in huntington lead to?

Answer 5

Translation of an expanded polyglutamine repeat sequence in the huntingtin gene (expressed throughout the body), the protein gene product the function of which is unclear - the expansion is thought to be a toxic.

Question 6

What does more CAG repeats indicate?

Answer 6

The earlier the onset of the symptoms

Question 7

What is the cause of the chorea in huntington disease?

Answer 7

• Progressive atrophy of the caudate nucleus and putamen
• This results in decreased ACh & GABA synthesis in the striatum
• GABA is the main inhibitory neuron so loss of this will result in decreased inhibition of dopamine which leads to excessive thalamus stimulation and excessive movements

Question 8

What are the risk factors of Huntington disease?

Answer 8

• Family history

- Having a parent with Huntington’s - child has 50% risk of getting it

Question 9

What is the presentation of Huntington disease?

Answer 9

• Often prodromal phase of mild psychotic and behavioural symptoms
• Then chorea develops (relentlessly progressive, jerky, explosive, rigidity involuntary movements - ceases when sleeping
• Can’t sit still
• May begin as general restlessness, unintentionally initiated movements and lack of coordination
• Dysarthria (unclear speech), dysphagia and abnormal eye movements
• Psychiatric problems
• Behavioural change - Aggression, addictive behaviour, apathy & self-neglect
• Depression/anxiety
• Dementia
• Associated with seizures
• Eventually to death - usually occurs within 15yrs of diagnosis, usually from an intercurrent illness e.g. infection

Question 10

What investigations can you do in suspected Huntington disease?

Answer 10

• Genetic testing - shows many CAG repeats - OVER 35:

- CT/MRI

Question 11

What is the treatment of Huntington’s disease?

Answer 11

There is no treatment for the disease progression

Question 12

What symptomatic treatment can be used in Huntington disease?

Answer 12

Benzodiazepines
Sulpirine - neuroleptic - depresses nerve function
Tetrabenazine - dopamine depleting agent

Also SSRI’s and antipsychotics