What is Huntington's Disease? It is a condition due to a dominant and faulty genetic disorder on chromosome 4.  The consequence of the fault with this gene starts around or just before middle age,  and leads to a gradual physical, mental and emotional change in its victim. Huntington's Disease was named after the American, Dr. George Huntington, because in 1872 he was the first person to document an accurate description of the symptoms and the route of the disease. The cause was then unknown.

 

Huntington's Disease - Hereditary Chorea

George Huntington (1850-1916)

George Huntington was born on 9 April 1850 in the drowsy secluded village of East Hampton, CT, United States. Both his father and grandfather were doctors, and George Huntington junior followed in their footsteps. At an early age, Huntington accompanied his father on his rounds and sick calls and during one of these visits, he gained his first experience of hereditary chorea.

At the time he called it Hereditary Chorea.  Chorea means involuntary jerky movements, from the Greek, for dance. Huntingtons is not so much a disease, but a condition or a syndrome, but was named at a time when a more precise rationale was lacking. The gene, which produces a protein, now called Huntingtin, was only discovered in 1993, and found to be a factor in this condition. Perhaps, an anti-Huntingtin protein could be produced, to combat this, then maybe not.   SEE BELOW

Huntingtin: The name of the gene responsible for Huntington's Disease or HD, and of the protein encoded by that gene. The molecular basis of HD is an increase in the number of a CAG triplet repeats, or poly-glutamines,  within the Huntingtin gene. The gene is on chromosome 4p16.3

The Huntingtin Mutation or gene change, is fully dominant. Male homo-zygotes - which have two copies of the Huntingtin gene, are no more severely affected than the female hetero-zygotes, which have only one copy of the gene. But it has long been recognized that paternal transmission, from the father, results in an amplified severity of the symptoms,  named the rigid-form. It also brings on an earlier commencement, or anticipation, with a more rapid progress than the maternal transmission from the mother's genes.

Men can develop HD in their early thirties, however, women are usually 10 - 15 years older.

HD gives rise to progressive, selective and localized, death or destruction of neuronal cells - neural cells, or brain-cells. The consequence of the loss of these vital cells is clearly associated with, or the cause of, the chorea or involuntary movements that come with the gradually decreasing psychomotor skills, and progressive dementia - the gradual mental deterioration.

Huntington Chorea a relatively rare, and invariably fatal, hereditary neurological disease that is characterized by irregular and involuntary movements of the muscles. Huntington disease is caused by a genetic mutation that causes degeneration of neurons in the basal ganglia, a pair of nerve clusters deep within the brain, that control movement. Symptoms usually appear between the ages of 35 and 50 and worsen over time. They begin with occasional jerking or writhing movements, called choreiform movements, or what appear to be minor problems with coordination; these movements, which are absent during sleep, worsen over the next few years and progress to random, uncontrollable, and often violent twitching and jerks. Symptoms of mental deterioration may appear including apathy, fatigue, irritability, restlessness, or moodiness; these symptoms may progress to memory loss, dementia, bipolar disorder, or schizophrenia. The disease was first described by the American physician George Huntington in 1872.

Sydenham Chorea  -  HD must not be confused with Sydenham Chorea, also called St. Vitus Dance, chorea-minor, infectious chorea , or rheumatic chorea, a neurological disorder characterized by irregular and involuntary movements of muscle groups in various parts of the body that follow streptococcal infection. The name St. Vitus Dance derives from the late Middle Ages, when persons with the disease attended the chapels of St. Vitus, who was believed to have curative powers. The disorder was first explained by the English physician Thomas Sydenham. Most often a manifestation of rheumatic fever, Sydenham chorea occurs most frequently between the ages of 5 and 15 years, and is more common in girls than boys. The disease may occur as an infrequent complication of pregnancy.

The symptoms of Sydenham chorea range in severity from mild to completely incapacitating. A vague deterioration in the ability to perform everyday tasks is replaced by involuntary jerking movements that are most obvious in the extremities and face but are also present in the trunk. Twitching movements are more noticeable on the limbs of one side of the body. The muscles of speech and swallowing may also be affected. Irritability, anxiety, and emotional instability, chiefly episodes of crying initiated by trivial incidents, are also common symptoms.

It is thought that Sydenham chorea is caused by a malfunctioning of the basal ganglia, groups of nerve cells in the brain. There is evidence that both the emotional manifestations and the abnormal movements of the disease are related to changes in the cerebral cortex. Attacks of Sydenham chorea tend to be self-limited, although the duration of each is several weeks; recurrence is frequent. Recovery is usually complete and is accelerated by bed rest. Sedation or the administration of tranquilizers may provide protection from self-injury in severe cases, when the patient is helpless.

Each child of a mother, or father, who has Huntington's Disease, has a 50% chance of  inheriting the disease. The condition does not skip a generation, like in many others. Anyone who inherits the dominant faulty gene will inevitably develop a form of HD, in its varying levels.

In some way - which is not yet understood - the faulty gene leads to a damage of only the, but very important, nerve cells in specific areas of the brain, including the the basal ganglia and cerebral cortex.

The gene fault is that the DNA gene sequence CAG, is erroneously repeated, and thus the programming of the brain's functions are changed, this leads to the onset of the symptoms seen. So instead of having what could be termed a normal gene - sequence, the chain is interrupted with an addition of a string of a CAG sequences, which acts almost like a glitch, bug or loop in the instructions. This repeat can be in chains of 10, or up to chains of 100. The symptoms, caused by the ultimate brain-cell loss, are usually quicker to come on, and quicker to bring death, the bigger the chain produced.

This glitch in the gene - sequence can start as early as the point of conception.

The loss of these brain-cells causes intense symptoms and eventually early death.

As the condition advances, it becomes more difficult for the patient to walk and speak. Memory and intellectual functions continue to decline, until the end. By far of the majority of patients are placed in hospices for special supervision. Care is for the most part, 24/7/52.

 HD can be inherited by one in 10,000 individuals in the Western World. Early and general signs of Huntington's Disease are mood swings, irritability, depression, memory loss, and gradual uncontrolled movements.

These early symptoms are in the main, of no surprise, as inevitably a parent may have also contracted HD, and now be dead.

In Genetics, the term Dominant Gene refers to the an allele that causes a phenotype  phenotype that is seen in a heterozygous genotype. Every person has two copies of every gene, one from mother and one from father. If a genetic trait is dominant, a person only needs to inherit one copy of the gene for the trait to be expressed. Dominant traits have a 50% chance to pass from parent to child. The fault in HD, is that the DNA gene sequence CAG, is erroneously repeated.

After the age of 21, a genetic test is available, this test will usually be able to show whether someone has inherited the faulty gene, but it will not indicate the age at which they will develop the disease, or when they will die, but this is usually about 15 years after the first symptoms show. 

Testing for the HD gene, necessitates a genetic test of the blood. The test analyzes the DNA for the Huntington's Disease mutation by counting the number of CAG DNA patterns  - CAG is a DNA sequence. The CAG sequence is repeated in the Huntington's Disease gene region, more than normal. 

A person will not generally get Huntington's Disease if their CAG repeats are lower than 30. If a person's CAG repeats are higher than 40 they will get Huntington's Disease. A person may or may not get Huntington's Disease if their CAG repeats are between 30 and 40.  However, a person is not in point of fact conclusively diagnosed with Huntingtons, until they show the specific symptoms.

Huntington's Disease is due to a dominant and faulty genetic disorder on chromosome 4.  A Chromosome is a threadlike structure several to many of which are found in the nucleus of plant and animal - eukaryotic cells. Chromosomes are composed of chromatin and carry the genes, which determine the individual characteristics of an organism. When the nucleus is not dividing, individual chromosomes cannot be identified with a light microscope. During the first stage of nuclear division, however, the chromosomes contract and, when stained, can be clearly seen under a microscope. Each consists of two chromatids held together at the centromere. The number of chromosomes in each cell is constant for and characteristic of the species concerned. In the normal body cells of diploid organisms the chromosomes occur in pairs; in the gamete-forming germ cells, however, the diploid number is halved and each cell contains only one member of each chromosome pair. Thus in man each body cell contains 46 chromosomes - 22 matched pairs and one pair of sex chromosomes,  and each germ cell 23. Abnormalities in the number or structure of chromosomes may give rise to abnormalities in the individual. 

Down’s Syndrome, and Huntington's Disease is the result of one such abnormality.

Bacterial and viral cells contain only a single chromosome; it differs from the eukaryotic chromosome in being much simpler, lacking histones and consisting simply of a single or double strand of DNA or - in some viruses,  RNA.

The six diseases linked to CAG repeat mutations include SCA2; Huntington's disease; spinocerebellar ataxia 1 (SCA1); dentatorubral-pallidoluysian atrophy (DRPLA); spinocerebellar ataxia 3 (SCA3 or Machado-Joseph disease); and spinobulbar muscular atrophy (Kennedy's disease). Three other diseases, fragile X syndrome, myotonic muscular dystrophy, and Friedreich's ataxia, are linked to different kinds of trinucleotide expansions.

Although there is no cure for Huntington's Disease, there are treatments for some symptoms. For the chorea or involuntary movements, a person with Huntington's Disease is likely to be prescribed a neuroleptic such as Tetrabenazine, Reserpine, Trilaton - Perhenazine, or Haldol. 

For depression, Fluoxetine, Sertraline Hydrochloride, or Nortriptyline are commonly used. Also, tranquilizers can be used to treat anxiety, and Lithium can be used for persons with severe mood swings. Speech therapy can also improve speech and swallowing, for a person with Huntington's Disease. 

The constant chorea, or shaking uses much more energy than normal. It is important that a person diagnosed with HD is given a very high calorie diet, not only to prevent weight loss, but it has also been shown to improve involuntary movement and behavioral problems. Food should not only be high calorie and highly nutritious, but cut very small or blended; foods should also be blended separately and given separately on the plate. It is unfair to just put ALL the patient's food in a blender together and expect them to enjoy it.

The Huntington’s Disease Society of America, Inc. (HDSA)