Huntington disease

1. Genetic disease

1. On chromosome 4

2. Caused by the expansion of a CAG trinucleotide repeat encoding a polyglutamine tract in the huntingtin protein. hhy

3. Provoke a severe neuronal loss of GABA cells in the striatum

4. While normal-size polyglutamine exists as a random coil, when expanded it acquires a “polar zipper” conformation with tendency towards self-interaction and aggregation. Indeed, intracellular aggregates of the mutant protein are a common feature of these disorders.

5. Polyglutamine inclusions are essentially found in nuclei

6. Progression of memory and executive deficits in HD as a function of length of the CAG triplet repeat mutation

7. Therapy with the injection of fetal or stem cells in the affected brain areas (striatum)

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• General outline    A prototypic mono-genic disease caused by abnormal repetition of DNA sequences and causing a progressive motor disorder accompanied by behavioural disturbances and cognitive impairment which eventually develops into dementia
  
• Synonyms    Huntington's Chorea
  
• Symptoms    Key features of Huntington's disease are hypotonic hyperkinesia (involuntary, exaggerated movements of the limbs) and hyopotonic. After few years, patients are unable to walk and to sit.
  Psychiatric symptoms include delusion, hallucinations, aggressivity, impulsiveness, personality changes, unsocial and obsessive behaviour.
  Cognitive impairment is frontal type including reduced verbal fluency, impaired executive functions and  particular memory problems.
  Course    Early onset: 30 - 40 (within families, onset becomes earlier every generation)
  Rapid progression of motor symptoms
  10-15 years
  
• Caregiver problems   
  
• Epidemiology    5 -10 / 100.000
  
• Aetiology    Huntington's disease is a monogenic disease. It runs in families. There is degeneration in subcortical nuclei, due to the toxicity induced by the abnormal repetition of DNA sequences (triplets).
  
• Diagnostic procedures    Reliable genetic tests: 99 per cent precise.
  Borderline cases
  
• Treatment and rehabilitation    Symptomatic treatment; neuroleptics for psychiatric symptoms; safety precautions
  
• Ongoing research    Brain grafts, injection of fetal brain cells into subcortical nuclei
  
• Available services    Huntington Disease Association in many European countries, European HD Association
  Further reading