huntingtons’s disease

Question 1

what are the symptoms

Answer 1

motor
- chorea
- dystonia
- loss of postural reflex
- bradykinesia
- rigidity

cognitive
- impulse
- disorganised
- repetition of words

metabolic
- weight loss
- sleep disturbance

psychiatric
- depression
- ocd
- anxiety

Question 2

how is it caused by

Answer 2

it is caused by a trinulceotide repeat disorder- this is caused by a repeat disorder, a mutation that causes re[eats leading to increase in the copy number until the gene becomes unstable

it occurs on the HTT gene which gives instructions to the protein huntington

Question 3

gene abnormality

Answer 3

expanded CAG trinucleotide repeat within the HUntington (HTT) gene on chromosome 4
in HD expanded HTT gene encodes mutant HTT protein
results in a gradual destruction at neurones

Question 4

what happens due to this mutation

Answer 4

protein aggregation - the mutating huntington protein has a a abnormal structure that predisposes it to aggregate into toxic clumps within neurones leading to the formation of inclusion bodies

these aggregated mutant HTT proteins interfere with normal cel;ulnar processes, disrupts signalling pathways, impair mitochondrial function and trigger oxidative stress - this dysfunction leads neuronal injury and cell death usually in the striatum and the cortex of the brain

these mutant HTT proteins also impair the balance of neurotransmitters in the brain leading to excessive activation of glutamate receptors causing excitotoxicity causing further damage to the neurones

impaired autophagy - this is the cell process responsible for clearing out damaged and dysfunctional components however this is impaired in HD, leading to neuronal degradation

transcriptional dysregulation - it also affects gene transcription, l;eading to wide spread changes in activity of various genes involved in neuronal function, survival and plasticity.

Question 5

clinical manifestations and potential treatments

Answer 5

1. tetraberazine - inhibitor of vascular monoamine transporter so reduce dopamine strorage , this is used to control involuntary hyperkinetic ( choreic movement)

hyperkinesia and psychiatric symptoms may respond well to pharmacology

treatment for chorea
- dopamine depleting agents
- valporic acid
- neuroleptics
- benzodiazepines

treatments for bradykinesia and rigidity
- levadopa
- dopamine agonists
- deep brain stimulation

treatment for depression
- SSRI’s