Huntington's disease

Huntington's disease or Huntington's chorea (HD) is an inherited disorder characterized by abnormal body movements called chorea, and loss of memory. It takes its name from the Ohio physician George Huntington who first described it precisely in 1872. The incidence is 5 to 8 per 100,000. more...

There is evidence that doctors as far back as the Middle Ages knew of this devastating disease.

Symptoms

Symptoms of the disorder include loss of cognitive ability (thinking, speaking), changes in personality, jerking movements of the face and body in general and unsteady walking. These symptoms develop into dementia and cognitive decline (not mental retardation which is an older term referring to the lack of development of mental ability rather than loss of it) and an advanced form of rapid jerking called chorea, the Greek word for dance.

The symptoms of Huntington’s disease begin insidiously. One-half to three-fourths of the patients present with abnormal movement or rigidity. The remainder of the patients present with mental status changes, such as irritability, moodiness, or antisocial behavior. All of the patients eventually exhibit chorea, which is jerky, random, uncontrollable, rapid movements. Typically, the abnormal movements begin at the extremities and then later progress.

Huntington's disease contributes to a chemical imbalance that leads many victims to commit suicide. This is also believed in part to be a result of the position in which sufferers find themselves.

Genetics

Huntington's disease is inherited in autosomal dominant fashion, meaning that it is a dominant allele. People with Huntington's disease have a 50% chance of passing the disease to each of their children.

The causative gene HD (one of the first identified to cause an inherited disease) is located on chromosome 4. Huntington's disease is inherited in an autosomal dominant fashion. The autosomal dominant fashion means that a recipient of the gene only needs one allele to inherit the disease. Most genetic diseases are autosomal recessive meaning that they need two alleles to inherit the disease. The dominant nature of Huntington's disease increases the chance of the disease occurring in offspring. A parent who has the disorder has a 50% chance of passing on the gene with each child.

The product of this gene is a 350 kDa cytoplasmic protein called huntingtin. The continuous aggregation of huntingtin molecules in neuronal cells gives rise to cell death, especially in the frontal lobes and the basal ganglia (mainly in the caudate nucleus) by some unknown mechanism. Huntingtin has a characteristic sequence of fewer than 40 glutamine amino acid residues (encoded by CAG trinucleotide repeats) in the normal form; the mutated huntingtin causing the disease has more than 40 residues. The severity of the disease is proportional to the number of extra residues.

While theories as to how the mutation brings about disease remain diverse and speculative, researchers have identified many specific subcellular abnormalities associated with the mutant protein, as well as unusual properties of the protein in vitro. Just as one example, in 2001, Max Perutz discovered that the glutamine residues form a nanotube¹ in vitro, and the mutated forms are long enough in principle to pierce cell membranes.

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