7. Huntington's Disease Flashcards
Define chorea.
A continuous flow of abnormal involuntary, jerky movements that are brief, abrupt, irregular, unpredictable, non-stereotyped and semi-purposeful.
Movements: flitting from one part of the body to another.
Patient appears fidgety/clumsy.
-> They may interfere with voluntary movements but cease during sleep.
What is Huntington’s Disease?
An autosomal dominant, incurable, progressive, neurodegenerative disorder
Explain the pathophysiology of Huntington’s Disease.
- It is an autosomal dominant genetic disorders which means one affected gene is enough to cause the disease.
- An affected person is normally present in each generation.
- CAG triple nucleotide repeat in HTT gene (Huntingtin) on CH 4 is repeated > 36 times for HD
[Normal = repeated 10-35 times] - Thought to be a toxic ‘gain-of-function mutation
- CAG codes for amino acid - glutamine
- Formation of abnormal proteins
- Aggregation of protein in neuronal cells in the caudate nucleus + putamen (make up the striatum) of the basal ganglia
- Causing striatal (GABAergic) neuronal cell death
- Progressive cerebral atrophy with marked striatal neuronal cell death - specifically GABAergic + Cholinergic neurones
- Results in decreased ACh + GABA synthesis in the striatum
- Results in decreased inhibition of dopamine release
- Results in excessive stimulation of the thalamus
- Results in abnormal excessive movement - chorea - & cognitive problems
Describe the inheritance pattern seen in Huntington’s disease.
Autosomal dominant inheritance.
In Huntington’s disease, what area of the basal ganglia is affected? Which neurotransmitter is affected?
- Striatum (caudate nucleus).
- GABA.
What triplet code is repeated in Huntington’s disease?
CAG triplet repeat.
> 36 repeats = HD.
Due to HD being a trinucleotide repeat disorder, what genetic feature does it display?
Explain it.
Genetic Anticipation.
This is where successive generations have more repeats in the gene, resulting in:
- Earlier age of onset
- Increased severity of disease
Give 2 early signs of Huntington’s disease.
- Irritability.
- Depression.
- Personality change.
It typically begins with cognitive, psychiatric or mood problems.
Give 3 later signs of Huntington’s disease.
- Chorea - fidgety.
- Psychiatric problems.
- Dementia.
- Chorea (involuntary, abnormal movements).
- Eye movement disorders.
- Saccadic eye movements. - Speech difficulties (dysarthria).
- Swallowing difficulties (dysphagia).
- Dementia.
Investigations for HD diagnosis.
- Diagnosis is mainly clinical
- Diagnosis is made in a specialist genetic centre using a genetic test for the faulty gene.
- It involves pre-test and post-test counselling regarding the implications of the results. - Genetic testing
- shows many CAG repeats (>36 CAG repeats) - CT/MRI:
- Shows caudate nucleus atrophy (loss of striatal volume)
What would an MRI scan of the brain of a patient with Huntington’s disease show?
Caudate nucleus atrophy - loss of striatal volume
How would you treat Huntington’s disease?
Nothing will stop progression - symptomatic treatment only.
- 1st line: Counselling for patient and family with carer support
- Speech and language therapy
- Genetic councelling for family
- Symptomatic treatment - for chorea:
- Benzodiazepines (e.g. diazepam)
- Antipsychotics/Neuroleptics (e.g. olanzapine, sulpride, haloperidol)
- Dopamine-depleting agents (e.g. tetrabenazine) - For depression:
- SSRIs
What is the prognosis like for Huntington’s disease?
- Prognosis is poor.
- Life expectancy = around 15-20 years after the onset of symptoms.
- Most commonly death is from concurrent illness e.g. pneumonia.
- Second most common cause is suicide.
