Huntington's Disease (High Dopamine ABCDE)

Question 1

Definition

Answer 1

Autosomal dominant genetic condition
Neurodegenerative disease = that causes repeated sequence of DNA forming abnormal proteins + progressive deterioration in the nervous system leading to abnormal movements and cognitive problems
- FULL PENETRANCE
- Lack of GABA + excessive nigrostriatal pathway

Question 2

Epidemiology

Answer 2

30-50

Question 3

Aetiology

Answer 3

“trinucleotide repeat disorder” that involves a genetic mutation in the HTT gene on chromosome 4 = CAG repeats (polyglutamine disease)

Question 4

Anticipation

Answer 4

This is where successive generations have more repeats in the gene, resulting in:

Earlier age of onset
Increased severity of disease

Question 5

Pathophysiology

Answer 5

Mutated protein aggravates in the neuronal cells of the caudate and putamen = which leads to neuronal cell death due to excitotoxicity which leads to high intracellular calcium.
Essentially too much dopamine
Associated with cell loss within the basal ganglia + cortex

Question 6

Signs (ABCDE)

Answer 6

Begins with cognitive, psychiatric or mood problems
- followed by development of movement disorders
Action
- HYPERKINESIA
Bad mood
- Depression
- Psychiatric issues
Chorea (involuntary, abnormal movements)
Dysarthria (Speech difficulties)
Dysphagia (Swallowing difficulties)
Dementia
Eye movement disorders

Question 7

Diagnosis

Answer 7

Clinical features
Fhx
Genetic testing if necessary (>35 repeats CAG on C4)

Question 8

Treatment

Answer 8

Extensive counselling
DA antagonists for chorea = tetrabenazine
Antipsychotics = olanzapine
Benzodiazepines = diazepam
Antidepressants = SSRIs