Huntington's Disease (High Dopamine)

Question 1

Definition

Answer 1

Neurodegenerative disease = autosomal dominant genetic condition that causes repeated sequence of DNA which causes an abnormal protein to form which causes the 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