Disease of Gentington
Contents:
Description:
Huntington disease (Huntington syndrome, chorea of Huntington or Gentington) — the genetic disease of a nervous system which is characterized by the gradual beginning usually at the age of 35-50 years and a combination of the progressing choreic hyperkinesia and mental disorders. The disease is caused by multiplication of a codon of CAG in IT-15 gene. This gene codes 350-kDa protein хантингтин with unknown function. At a gene of wild type (not mutant) different people have a different number of CAG of repetitions, however, when the number of repetitions exceeds 36, the disease develops. The neuromorphological picture is characterized by a striatum atrophy, and at a late stage also an atrophy of a cerebral cortex.
Symptoms of the Disease of Gentington:
Symptoms of a disease of Huntington can be shown at any age, but to a thicket it occurs in 35–44 years. At early stages there are little changes of the personality, cognitive abilities and physical skills. Usually the first find physical symptoms as cognitive and mental disorders are not so expressed in early stages. Almost at all patients Huntington disease finally is shown by similar physical symptoms, but the beginning of a disease, progressing and extent of cognitive and mental disturbances differ at individuals.
To start a disease the chorea — the random, uncontrollable motions is most characteristic. The chorea at the beginning can is shown in the form of concern, small involuntary or incomplete movements, a lack of coordination and delay of spasmodic movements of eyes.
Right at the beginning usually there are problems because of physical symptoms which are expressed in the sharp, sudden and not giving in to control movements. In other cases, on the contrary, the patient moves too in a slowed-up way. There are lacks of coordination of movements, the speech becomes muffled. Gradually all functions demanding muscular control are broken: the person begins to grimace, has problems with chewing and swallowing. Because of the bystry movement of eyes there are sleep disorders. Usually the patient passes through all stages of physical frustration, however influence of a disease on cognitive functions at all very individually. Most often there is a disorder of abstract thinking, the person stops being capable to plan the actions, to conform to the rules, to estimate adequacy of the actions. Gradually there are problems with memory, there can be a depression and panic, emotional deficit, an egocentrism, aggression, obsessions, problems with recognition of other people, hyper sexuality and strengthening of addictions, such as alcoholism or a game addiction.
Etiologies of Gentington:
The gene хантингтин (HTT), present at all people, codes protein хантингтин (Htt). The gene of HTT is located on a short shoulder of the 4th chromosome (4p16.3). This gene consists of the sequence of three nitrogenous bases — цитозин, which repeat a set of times (i.e.... TsAGTsAGTsAG...) also are known as trinukleotidny repetitions. The triplet of TsAG codes amino acid a glutamine therefore synthesizable protein хантингтин consists of a chain of the glutaminic amino acids called a polyglutaminic path.
The quantity of TsAG of triplets variously at individuals can also change with succeeding generations. If them becomes more than 36, then the extended polyglutaminic path is synthesized and there is a formation of mutant protein of a hantingtin (mHtt) which has toxic effect on cells and causes Huntington disease. As a rule, extent of damages depends on number of TsAG of repetitions, existence about 60% of repetitions causes emergence of symptoms at various age much. 36-40 repetitions result in the reduced penetrance of a form of this disease which is shown much later and more slowly progresses. In certain cases the onset of the illness can be so late that symptoms are never found. At very large number of repetitions, Huntington disease has full penetrance and can be shown up to 20 years, then the disease is classified as juvenile, akinetically - rigid or Vestfal options. Makes about 7% of cases of a disease of Huntington.
The mutant gene was presumably delivered in the USA in 1630 by two brothers who emigrated from Essex to Boston.
Treatment of the Disease of Gentington:
Huntington disease is incurable, but there is a treatment capable to facilitate some symptoms.
Tetrabenazin was developed especially for reduction of weight of symptoms of a disease of Huntington, approved in 2008 in the USA. Neuroleptics and benzodiazepines help to reduce manifestations of a chorea. Amantadin and ремацемид are in a research stage, but showed positive takes. For simplification of a hypokinesia and muscle tension appoint protivoparkinsonichesky drugs, for simplification of a myoclonic hyperkinesia - valproic acid.
Apply selective serotonin reuptake inhibitors to elimination of a depression and миртазапин, and at psychoses and behavior disorders appoint atypical anti-psychotics.
