Huntington's disease: what is it, the first symptoms and signs, treatment, prognosis

What is Huntington's disease?

Huntington's disease (Huntington's syndrome, Huntington's chorea or Huntington's chorea) is a genetic, progressive neurodegenerative disease characterized by the gradual development of involuntary muscle movements affecting the arms, legs, face and trunk, and progressive deterioration of cognitive processes and memory (dementia).

Neurological movement abnormalities can include uncontrolled, irregular, rapid, abrupt movements (chorea, choreic hyperkinesis) and athetosis, a condition characterized by relatively slow, writhing involuntary movements. Dementia is usually associated with progressive disorientation and confusion, personality disintegration, impaired memory control, anxiety, agitation, and other symptoms and signs. In patients with the disorder, the duration of the disease can vary approximately 10-25 years or more. Life-threatening complications can result from

pneumonia or other infections, injuries associated with falls, or other related processes as a result of illness.

Huntington's chorea is transmitted as an autosomal dominant trait. The disease occurs as a result of changes (mutations) in a gene HTT. Gene HTT, located on the short arm (p) of chromosome 4 (4p16.3) encodes a protein known as Huntingtin. This gene contains a region with a repeating sequence of three nucleotide bases - cytosine-adenine-guanine (ie, CAGCACCAG ...). The length of the extended repetitions can influence the age at which symptoms appear. Specific symptoms and physical signs associated with Huntington's disease result from degeneration of nerve cells (neurons) in certain areas of the brain (eg, basal ganglia, cortex brain).

Signs and symptoms

Signs and symptoms of the disease (see. video) most often appear in adults aged 30-50 years, but can appear at any age. Symptoms tend to get worse over 10-25 years.

Over time, Huntington's disease or its complications are fatal.

According to the American Society for the Control of Huntington's Disease, symptoms of the disorder may be similar to amyotrophic lateral sclerosis (BASS), Parkinson's disease and Alzheimer's disease - all in one.

The main symptoms include:

• personality changes, mood swings and depression;
• problems with memory and judgment;
• unsteady walking and uncontrolled movements (choreic hyperkinesis);
• difficulty speaking and swallowing;
• weight loss.

How the signs and symptoms of the disease progress depends on the individual. In some people, depression occurs before motor skills are affected. Mood swings and unusual behavior are usually the first to show.

- Early signs and symptoms.

Early symptoms may not be recognized if the disorder has not previously occurred in the family. It can take a long time to establish a diagnosis.

Initial signs and symptoms include:

• light uncontrolled movements;
• small changes in coordination;
• minor mood changes;
• lack of attention, slight problems with concentration and difficulty in work;
• blackouts in short-term memory;
• depression;
• irritability.

The patient may lose motivation and focus, and appear lethargic.

- Middle and late stage.

Symptoms become more severe over time.

These include physical changes, loss of movement control, and emotional and cognitive changes.

- Physical signs.

The patient may experience:

• Difficulty communicating, including finding words and illegible speech
• weight loss leading to weakness;
• Eating and swallowing problems because the muscles in the mouth and diaphragm may not be able to respond
• the risk of choking, especially in the later stages;
• uncontrolled movements.

There may be uncontrolled body movements, including:

• uncontrolled facial movements;
• twitching of parts of the face and head;
• clicking or fidgeting movements of hands, feet.

As the disease progresses, uncontrolled movements occur more often and with greater intensity. They can become slower over time as the muscles get stiffer.

- Emotional changes.

Emotional signs may alternate rather than occur sequentially.

They include:

• aggressiveness;
• anger;
• antisocial behavior;
• apathy;
• depression;
• excitement;
• panic;
• disappointment;
• lack of emotion becomes more and more evident;
• dejection;
• stubbornness;
• cognitive changes.

You may experience:

• loss of initiative;
• loss of organizational skills;
• disorientation;
• trouble focusing attention;
• problems with multitasking.

- Late stage.

Over time, the patient can no longer walk or talk and needs complete care.

However, sufferers tend to understand most of what is said and recognize friends and family members.

Causes of Huntington's disease

The disease is inherited as an autosomal dominant trait. Human traits, including classic genetic diseases, are the product of the interaction of two genes, one of which is passed on from the father and the other from the mother.

In dominant disorders, one copy of the disease gene (obtained from the mother or father) will be expressed as "dominant" over the other normal gene and leading to the onset of the disease. The risk of transmission of the disorder from the affected parent to the offspring is 50% with every pregnancy, regardless of the sex of the child.

Huntington's chorea is caused by changes (mutations) in a gene located on the short arm (p) of chromosome 4 (4p16.3). Chromosomes are found in the nucleus of all cells in the body. They carry the genetic characteristics of every person. Pairs of human chromosomes are numbered 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm (shoulder), denoted by the letter "p", and a long arm, denoted by the letter "q". Chromosomes are further subdivided into numbered bands.

This gene, known as HTT, controls the production of the Huntingtin protein, which is found in nerve cells (neurons) throughout the brain. However, the specific function of the protein is unknown. In patients, the gene HTT contains errors in the coded "building blocks" that carry its specific genetic instructions.

The instructions in each gene are composed of different patterns of four basic chemicals (nucleotide bases) called adenine (A), cytosine (C), guanine (G), and thymine (T). In people with the disease, the gene HTT contains abnormally long repeats of encoded instructions, consisting of cytosine-adenine-guanine (expansion of trinucleotide CAG (CAG) repeats). For example, patients with the disease have more than 35 CAG repeats in the gene HTT, with the majority having more than 39. However, people without the disorder have about 20 repeats in the gene.

The specific symptoms associated with Huntington's disease are caused by degenerative changes in nerve cells (neurons) in specific areas of the brain, including the basal ganglia and cerebral cortex. The basal ganglia are specialized nerve cells deep in the brain that play a role in regulating movement. The cerebral cortex, the outer region of the brain, is responsible for conscious thinking and movement.

Affected populations

Huntington's disease affects 3-7 per 100,000 people of European descent. The disorder appears to be less common in some other populations, including people of Japanese, Chinese, and African descent. Symptoms usually develop in the adult age of 30-50 years. The disease progresses slowly, and the patient can live another 10-25 years after the onset of symptoms.

Diagnostics

Because symptoms are mild in the early stages of Huntington's disease, it can be difficult to recognize its onset. The suspicion may be based on symptoms and on the presence of the disease in the patient's relatives. The doctor should be informed about relatives who have had mental disorders or who have been diagnosed with neurological or mental disorders diseases (for example, Parkinson's disease or schizophrenia), since the disease in these relatives could be confused with another nervous or mental disease.

To rule out other diseases and detect degeneration of the basal ganglia and other areas of the brain, which usually affects the disease, have computed tomography (CT) or magnetic resonance imaging (MRI).

Additionally, a genetic analysis is performed to confirm the diagnosis. For people who do not have symptoms of Huntington's disease, but whose family has had cases of this disease, it is important to undergo genetic testing and counseling. The fact is that such people can have children before the first symptoms appear. Genetic counseling should precede genetic testing. For consultation, such people are referred to a center specializing in solving complex ethical and psychological problems associated with genetic research.

Symptomatic Disorders

Symptoms of the following disorders may be similar to those of Huntington's chorea. Comparisons can be useful for differential diagnosis:

• Hallerwarden-Spatz disease Is a rare progressive disorder that affects muscle movement. The disorder is related to the degeneration of the nervous system. Hallerworden-Spatz disease is characterized by uncontrolled muscle movements (dystonia), muscle rigidity, and loss of cognitive ability (dementia). Symptoms usually begin in childhood, although sometimes the disease begins in adulthood.
• Multiple systemic atrophy (MCA) is a group of rare hereditary diseases characterized by progressive degeneration of the cerebellar cortex and other brain tissues. Several different types of systemic atrophy have been identified, the symptoms of which vary widely depending on the type of MSA. As a rule, these disorders are characterized by impaired ability to coordinate muscle movements, tremors, involuntary muscle twitching, speech impairment (dysphasia), loss of cognitive ability, and impairment psyche.
• Rheumatic chorea (Sydenham's chorea) - a disorder of the nervous system that occurs suddenly after a streptococcal infection, for example, after scarlet fever, pharyngitis or rheumatic fever. The disorder usually affects young children and adolescents. Sydenham's chorea is characterized by rapid, involuntary, non-repetitive muscle movements that can gradually become more severe and frequent. The muscles of the arms and legs are most severely affected. Speech can also be impaired. Other common symptoms may include an awkward gait. Chorea-like muscle movements tend to disappear with sleep. The disorder usually resolves in 3-6 months without permanent neurological or muscle damage.
• Wilson's disease Is a rare genetic disorder characterized by an excess of copper in various tissues of the body, especially in the liver, brain and corneas of the eyes. The disease is progressive and, if left untreated, can cause liver disease, central nervous system dysfunction and death.
• Tourette's syndrome - a neurological movement disorder that usually first appears between the ages of 2-16 years. Rapid blinking of the eyes (nystagmus) or facial tics. Tourette's syndrome is not a progressive or degenerative disease and patients live a normal life expectancy.

Treatment for Huntington's disease

After Huntington's disease is diagnosed, it is advisable for the patient to draw up preliminary medical instructions in case of disability as soon as possible. In these instructions, the patient can explain what kind of medical care he would like to receive at the end of his life.

There is no cure for Huntington's disease. However, some drugs, including antipsychotics (such as chlorpromazine, haloperidol, risperidone, and olanzapine), and drugs that reduce amounts of dopamine (such as tetrabenazine and the high-pressure drug reserpine) can help relieve symptoms such as abnormal movements and excitation.

Antidepressants can be used if you are depressed.

Forecast

Huntington's disease is a progressive disability and death, usually from an intercurrent illness.

The average age of death in all major categories ranges from 51 to 57, but the range could be broader. The duration of the illness varies considerably, with an average of about 19 years. Most patients survive for 10-25 years after the onset of the disease. In a large study, pneumonia and cardiovascular disease were the most common primary causes of death.

The juvenile form of the disease (i.e., the onset of the disease in patients under 20 years of age) accounts for approximately 5-10% of all patients. Most patients with juvenile Huntington's chorea inherit the disease from their father, while patients with onset after 20 years of age are more likely to inherit the gene from their mother.