Huntington’s Disease – At A Glance

Huntington’s disease is an autosomal dominant inherited triple repeat (CAG) disorder that causes progressive destruction of the brain cells, predominantly affecting the corpus striatum of basal ganglia and cerebral cortex.

It is a degenerative disease, usually presenting at the age of 30 – 50 years, where symptoms gradually progress death occurs after 10 – 20 years of diagnosis.

Unfortunately, there is no cure for Huntington’s disease and therefore it is fatal disease.


Inheritance Of Huntington’s Disease


There is 50% chance that the offspring will get the disease and pass to future generations
There is 50% change that the offspring will never get the disease
Affects both males and females equally


Genetic Anticipation

  • This depends on the number of CAG repeats
  • In each generation the number of CAG repeats increases
  • Therefore the age of onset of HD, reduces over generation to generation 
    • Ex : Father developed symptoms at the age of 60 year, but his son develops symptoms at the age of 50 years 
  • Anticipation is seen prominently when father is affected 


Pathophysiology Of Huntington’s Disease

Autosomal dominant disease – Presence of Huntington gene
                   
Genetic mutation of chromosome 4, produces Huntington proteins
Huntington gene has excess CAG repeats that codes excess glutamin molecules in the Huntington protein
Normal individuals have less 35 CAG segments, but in HD there are more than 35 CAG segments
Hence called Triple repeat disorder
                   
Huntington protein aggregate in basal ganglia, specially in the corpus striatum of the basal ganglia, including the caudate and putamen
                   
Damage to the neurones by….

  • Excitotoxicity
  • Oxidative stress
  • Imparied energy productive
  • Apoptosis
                   
Damage to basal ganglia, leads to involuntary movements (Chorea)
                   
Later affects other parts of the brain 



Presentation Of Huntington’ Disease
  • Usually present at 30 – 50 years of age
  • Characterized by motor dysfunction, cognitive impairment and behavioural changes
  • Weight loss
     
  • Early stage  
    • Subtle chorea
    • Difficulty in concentration
    • Memory lapses / Short term memory loss 
    • Abnormal eye movements
    • Depression
       
  • Intermediate stage
    • Chorea worsens
    • Cognitive impairment worsens 
    • Impaired speech 
    • Dysphagia
    • Bradykinesia
    • Rigidity
    • Postural instability 
    • Bipolar disorder
       
  • Late stage
    • Severe dementia 
    • Variable reflexes
    • Spasticity
    • Clonus
    • Extensor planter response (Advanced cases only)

  • Motor involvement 
    • Chorea
    • Rigidity
    • Abnormal eye movements
    • Postural instability 
    • Impaired gait
    • Dysphagia
       
  • Cognitive involvement
    • Difficult in concentration
    • Memory impairment / Dementia
    • Impaired judgement
       
  • Behavioral involvement
    • Depression
    • Bipolar disorder 


Complications Of Huntington’s Disease

  • Aspiration pneumonia
  • Repeated falls


Investigations Of Huntington’s Disease
  • Genetic testing is diagnostic
  • MRI 
    • Bilateral caudate nucleus atrophy
    • Enlarged ventricles 



Treatment Of Huntington’ Disease

Aim is to improve the quality of life by treating acute problems

  • Depression – Antidepressants
  • Bipolar disorders – Mood stabilizers 
  • Physiotherapy, occupational therapy to improve mobility
  • Speech therapy
  • Improve nutrition
  • Environmental modifications to help the patient 


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