Huntington's Disease

From The School of Biomedical Sciences Wiki
Jump to: navigation, search

Huntington's Disease (HD) is an example of a trinucleotide repeat neurodegenerative disease. It is an autosomal dominant disorder, requiring only one gene from either parent's genotype in order to be expressed in the phenotype. This disorder is caused by an autosomal dominant mutation in one of the copies of the Huntingtin gene (located on the short (p) arm of chromosome 4). Because of this, there is a 50% chance that the child of an affected person will inherit the disease. The Huntingtin gene (HTT) codes for the protein Huntingtin (Htt), and part of this gene is a repeated section called a trinucleotide repeat, which can have different lengths depending in the individual. However, when the size of this trinucleotide repeat section reaches a certain threshold, it starts making and altered form of the protein. This mutant form is called mutant Huntingtin protein (mHtt) and it gradually damages cells in the brain. In other words, this mutant form permors different functions, which lead to pathological changes expressed as the disease symptoms [1].

This condition is genetically dominant and almost fully penetrant: a mutation in one of the two HTT genes causes the disease.Huntington's Disease is not linked to sex, but the length of the trinucleotide repeat can be influenced by the sex of the affected parent.

It is more frequent in people from Western Europe than those from Asia or Africa, and it can affect both male and female.

Symptoms

Tipically, there is a progression in the disease and it gets worse for around 10 to 20 years until the person eventually dies. There is no common pattern in the symptoms.

The main symptoms of HD include dementia and motor function issues (akin to Parkinson's Disease), the severity of which increase rapidly as the disease develops. Behavioural changes: lack of emotions; antisocial behavior; difficulty concentrating on more than one task; memory lapses; orientation problems. Psychiatric problems: depression; obsessive behavior. Movement problems: uncontrollable movements; over time movements become slow and muscles more rigid. Feeding problems: weight lost because mouth and diaphragm muscles do not work properly; problem in swallowing. Communication problems: difficulty putting thoughts into words; impaired breathing can make speech difficult. Sexual problems: loss of interest or, less commonly, making inappropriate sexual demands. End of life: the person will be totally dependent and need full nursing care. Death is usually from a secondary cause, such as heart failure, pneumonia or another infection [2].

Treatment

There are no known cures for Huntington's disease for the time being, however there are speculations that excitotoxic drugs or neural transplantation will hold the key to slowing down the course of the illness and treating the dementia symptoms.  The drugs used to alleviate the motor symptoms include tetrabenazine - which reduces dopamine storage, chlorpromazine - a dopamine antagonist and baclofen - a GABA agonist. NB - these drugs are essentially the opposite of those used to treat Parkinsons Disease [3]

References

  1. Walker FO (2007). "Huntington's disease". Lancet 369 (9557): 218–28 [221]
  2. http://www.nhs.uk/Conditions/Huntingtons-disease/Pages/symptoms.aspx
  3. Dale M.M, Flower R.J, Henderson G, H.P Rang, Ritter J.M (2011) 'Rang and Dale's Pharmacology' 7th Ed. (Elsevier Churchill Livingstone)
Personal tools
Namespaces
Variants
Actions
Navigation
Toolbox