The disease of the Saxon causes. Tay Sachs disease: diagnostic procedures and treatment regimen

GM 2 gangliosidosis (Tay-Sachs disease) is a disease with an autosomal recessive type of inheritance that affects the central nervous system (spinal cord and brain, as well as meningeal membranes). During the first six months of life, children develop normally with this disease, and then brain function begins to suffer, and they more often die before the age of 3-4 years.

The incidence rate is about 1 case per 250,000 population.

Classification of Tay-Sachs disease

• Children's uniform: after six months after birth, children experience a continuous deterioration in physical and mental abilities: blindness, deafness, cannot swallow. Muscles atrophy and paralysis sets in. Death occurs before the age of 3-4 years.
• Teenage form: motor-cognitive problems develop, problems with swallowing (dysphagia), with speech (dysarthria), unsteadiness of gait (ataxia), spasticity. Patients die before the age of 15-16 years.
• adult form: occurs at the age of 25 to 30 years, characterized by gait disturbance, progressive deterioration of neurological functions. Typical symptoms are: problems with swallowing and speech, unsteady gait, cognitive decline, spasticity, the onset of schizophrenia in the form of psychosis.

Causes of Tay-Sachs disease

The disease develops due to a genetic defect that leads to impaired synthesis hexosaminidase A, a chemical mediator (enzyme) located in the lysosomes of cells and necessary for the conversion, storage, use of substances, as well as the disposal of metabolic products of certain substances (lipids, or gangliosides) in the central nervous system. In the absence of the enzyme, these substances accumulate in the neurons of the brain, disrupting their work and then destroying them.

Tay-Sachs disease is transmitted to children through a pathological gene located on chromosome 15 from parents. If both carriers of the gene have a child, then the risk of having an affected child in each pregnancy is 25%. A child may inherit only one gene in 50% of cases and become a carrier, but in 25% of cases he will not inherit this gene at all, will not be sick or a carrier.

Thus, the inheritance of Tay-Sachs disease often occurs hidden (in an autosomal recessive manner) from generation to generation.

Symptoms of Tay-Sachs disease

An early sign of Tay-Sachs disease is hypersensitivity the baby to loud sounds, as well as an unusual reaction to them. The first symptoms are also stunted growth and development. The patient loses interest in the environment, in family members, acquired skills, for example, the child stops crawling. After some time, the child goes blind, retarded in mental development; muscle functions are reduced until they are lost, including the ability to move, eat and drink, and make sounds. Seizures may occur in later stages.

After 10 months, the disease actively progresses. The child has seizures, muscle atrophy and vision loss. An attack is a flash of abnormal sudden electrical activity of the brain that affects the functioning and control of the motor apparatus, distorts visual images, speech and psychological perception of reality. The degree of damage is individual. In some cases, the child falls to the floor, convulsing when the muscles are strongly contracted with the occurrence of involuntary twitching of the limbs. Others are in a state of trance, with only a few muscles remaining mobile. Sometimes patients see images or smells that are uncharacteristic of a healthy person.

In the final stages of the disease, tube feeding may be required. In this state, there is practically nothing to help the child, with the exception of support and care, treatment of concomitant infections that weaken the child. The cause of death is often pneumonia (pneumonia) or another infection.

If there is suspicion of Tay-Sachs disease, you need to pay attention to the symptoms:

In a 3-6 month period:

• Difficulty focusing on a subject.
• Deterioration of visual perception in a child.
• Eye twitching.
• Unreasonable pronunciation of rather loud sounds.

In a 6-10 month period:

• Reduced activity.
• Hypotension (decreased muscle tone).
• It is difficult to sit, roll over, motor skills are dulled.
• Reduced vision.
• Hearing loss, gradually leading to deafness.
• Macrocephaly (increased head size).

After 10 months:

• Blindness.
• Mental retardation.
• Paralysis.
• Swallowing disorders, breathing difficulties, seizures.

Diagnosis of Tay-Sachs disease in Israel

• Ophthalmoscopy:"cherry" spot of the macula, detected on the retina of the eye. This is an area of ​​the retina with an increased accumulation of gangliosides in retinal ganglion cells. Thus, it is the cherry spot of the macula that is the part of the retina that provides normal vision.
• Microscopic analysis of neurons: these cells loaded with gangliosides are stretched.
• Screening, carried out in two ways:
  • Carrier Detection Test: reveal whether a person is a carrier of 1 copy of the mutation.
  • Prenatal testing: determines whether two defective copies of the gene fetus have inherited, one each from the parent. This test can be done via analysis of HEXA enzyme activity in embryonic cells obtained by chorion biopsy or after amniocentesis. A more precise study, namely the polymerase chain reaction (PCR), can be done to analyze mutations.
  • Study of enzymatic activity: the level of hexosaminidase A in blood serum, in leukocytes is lowered.
  • Polymerase chain reaction : a study of DNA (a substance that contains genetic information, is embedded in the nucleus of body cells) for the presence of mutations.

Treatment of Tay-Sachs disease in Israel

• • Not effective treatment and drugs for Tay-Sachs disease.
  • Even with the best care, children with childhood forms die before the age of 5, but the course of the adult form can only be slowed down.
  • Patients receive palliative care to relieve symptoms.
  • Feeding tubes are inserted as children cannot swallow food.

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Image from lori.ru

Tay-Sachs disease, or infantile gangliosidosis, along with Gaucher's disease, belongs to hereditary disorders in the lipid metabolism system.

The basis of Tay-Sachs disease is a genetically determined disorder in the metabolism of special lipids - gangliosides. It is accompanied by their increased deposition in the gray matter of the brain, exceeding the norm by 300 times. In addition, gangliosides accumulate in the liver and spleen. The basis of the disease is a deficiency of one of the forms of enzymes that control lipid metabolism (hexosaminidase A). Rare: 1 in 250,000. It is inherited in an autosomal recessive manner. The gene defect is localized on the fifteenth chromosome.

Symptoms of Tay-Sachs disease

Found in children early age, although at birth the first 4 months, children are no different from their peers. Gangliosidosis develops slowly, the child gradually shows less activity, loses previously acquired skills, ceases to be interested in toys and recognizes the mother, the character of the child's crying changes, becoming drawn out and weak. Disorders of the visual analyzer are the first to appear, the child does not fix his gaze and does not follow the object. Blindness develops quite quickly, often in parallel with deafness. start to progress and mental disorders, the degradation of intelligence is quickly noted, up to idiocy. Muscle hypotension is formed, the child stops holding his head, paralysis in the limbs, convulsions with the manifestation of opisthotonus, which are provoked by minimal external stimuli - light, sound. In parallel, pseudobulbar paralysis is formed: the act of swallowing is upset, violent crying or laughter occurs. Children quickly lose weight, after a year and a half there is a fatal outcome.

Diagnosis of Tay-Sachs disease

The diagnosis is based on an indication of similar cases in the genus, clinical manifestations, results biochemical research- determine the activity of the enzyme in blood leukocytes and tissue. In addition, there are typical changes in the fundus of the eye in Tay-Sachs disease - atrophy of the nipple. optic nerve and cherry spot in the macular area.

There is no specific treatment for Tay-Sachs disease. Prescribe drugs to maintain the liver, a complex of vitamin therapy, anticonvulsants. Highest value given to prenatal diagnosis of the disease with early termination of pregnancy.

Rare and dangerous Tay-Sachs disease - when genes kill

Tay-Sachs disease has several names: infantile gangliosidosis or early infantile idiocy amavrotic.

This disease belongs to hereditary diseases. nervous system and is quite rare.

The disease got its name in honor of the two doctors who discovered it - Warren Tey (an ophthalmologist from Britain) and Bernard Sachs (a neurologist from America).

The development of the disease depending on age

There are three forms of the disease:

Causes of the disease

The causes of the disease lie in disorders at the genetic level that occur in the metabolism of gangliosides. These special lipids, exceeding 300 times the norm, are concentrated in the gray matter of the brain.

Accumulation also occurs in the liver and spleen. The disease is based on a deficiency of one of the types of enzymes that affect lipid metabolism (hexosaminidase A).

The disease occurs in the ratio: 1 in 250,000. Basically, this disease affects the population of ethnic groups, for example, the French, whose place of residence is Canada.

Jews of Eastern Europe are also susceptible to the disease, in which the incidence is higher - 1 per 4,000 people.

This disease develops in the baby who got two genes with a defect, that is, the disease is inherited in an autosomal recessive manner. What does it mean?

A child inherits genes from the father and from the mother in the same amount. If one or both chromosomes from a pair are affected, then they speak of the occurrence genetic disease. In people with Tay-Sachs disease, both chromosomes in a pair are defective.

This disorder is called an autosomal recessive disorder. If one of the parents has a defective gene, the baby will be healthy, but with a 50% chance it will be a carrier, which jeopardizes the health of his heirs in the future. In the presence of a gene with a defect in both parents, three scenarios are possible.

Driving force for development this disease is the gradual accumulation in the nervous system of gangliosides - substances that affect the normal functioning of the cells of the nervous system.

All sick children have a damaged gene responsible for the complete synthesis of hexosaminidase enzymes.

A child's body with a congenital disease cannot continuously process fatty substances, so they accumulate and then deposit in the brain.

This leads to the fact that the activity of nerve cells is blocked and severe consequences occur for the whole organism. In the body of a healthy child, gangliosides are constantly synthesized and broken down.

Pathology is diagnosed in babies at the age of about six months, since up to four to five months the child develops quite normally, like all children of this age.

The first symptoms of Tay Sachs disease are that the child loses contact with the outside world, his gaze is constantly focused in one direction, the baby does not want anything, he becomes apathetic, he has no reaction to objects, sounds, familiar faces.

He has an increased reaction only to loud and sharp sounds. Even when the baby looks quite healthy, parents and relatives often notice that the child shudders sharply with his whole body at loud auditory stimuli.

Friedreich's hereditary ataxia causes serious disorders of the nervous system - causes, symptoms and treatment of pathology.

The second stage of the disease is a regression in the development of the child: the acquired skills are lost, he refuses to crawl, sit, becomes passive, toys do not cause any interest, mental retardation occurs, at the same time the size of the head increases significantly, the baby begins to lose sight, and often hearing.

At a later stage between the first year of life and the second year of life, the baby is more likely to experience seizures, manifested in the form of convulsions and paralysis.

Babies do not gain weight, but rapidly lose it. With this development of the disease, the child rarely survives to the age of five.

Signs of illness in adults

The adult form is very rare and occurs in patients in their 20s and 30s. It usually does not have a fatal outcome.

The disease manifests itself in gait disturbance and rapid deterioration of neurological functions. With such a disease, an adult can live after the diagnosis is established for 10-15 years.

Diagnosis of the disease

Before determining the diagnosis, the doctor examines the results of the studies, asks the parents in detail about the clinical manifestations, and finds out if there have been cases of this disease in the family.

The doctor will definitely refer you to an ophthalmologist for examination, since typical manifestation disease is the location on the retina of the red spot, which can be determined using an ophthalmoscope.

There are also changes in the papilla of the optic nerve: it atrophies.

It can not be cured, it is necessary to support

Treatment of Tay-Sachs disease must begin before the onset of neurological signs. Use blood transfusion, plasma.

There are no drugs and specific methods that cure Tay-Sachs disease.

The latter are often ineffective against seizures that occur with this disease. Health care is to simply alleviate the symptoms of the manifestation of the disease, but if we are talking about a late form, then to a delay in the development of the disease.

The prognosis for this disease is unfavorable.

Disease prevention

To prevent the disease, spouses who want to have children must be tested for the presence of the gene for this disease if at least one of the spouses had cases of Tay-Sachs disease in the family.

If such a gene is found in both spouses, then they are categorically not recommended to conceive children. It happens that during the examination the woman is already carrying a child, then a special procedure is prescribed to identify the defective gene in the child - amniocentesis.

For this laboratory research amniotic fluid obtained by taking a puncture of the amniotic membrane is exposed. If the defective gene is found, the pregnancy must be terminated.

If the future parents have accurate information that they are carriers of the defective gene, and pregnancy has already occurred, then it is necessary to undergo a screening test at the twelfth week.

To conduct research, doctors take blood from the placenta to find out if the future baby has inherited mutant genes.

Future parents need to be responsible for their own health and the health of their future children and follow all the recommendations of doctors.

Prenatal diagnosis during each pregnancy enables a married couple to give birth to healthy children.

Tay-Sachs disease is an extremely rare hereditary disease that has autosomal recessive inheritance and is characterized by CNS damage.

This disease, which belongs to the group of lysosomal storage diseases, is also known as early childhood amaurotic idiocy or GM2 gangliosidosis. The probability of having a child with this disease reaches 25% if the mother and father have a mutant gene.

Tay? Sachs disease is widespread among Ashkenazi Jews. They have approximately 3% of the population with the mutant HEXA gene. In addition, the disease is relatively common in Cajuns and French Canadians. As for other population groups, the average frequency of carrying such a gene is only 0.3%.

Etiology and pathogenesis

Mutation of the HEXA gene, which is responsible for the synthesis of the enzyme hexose aminidase A (a mediator catalyst involved in the utilization of gangliosides in the CNS), leads to a genetic defect. If the enzyme is absent, gangliosides begin to accumulate in the neurons of the brain. As a result, the functioning of neurons is disrupted, which further leads to their complete destruction.

Tay's disease? Sachs (amaurotic idiocy) comes in three forms:

In the first form of the disease, death occurs at 3-4 years. In the adolescent form of the disease, death is guaranteed at 15–16 years of age.

Symptoms of Tay? Sachs disease are associated with CNS damage. Newborns with this hereditary disease develop normally for the first six months. At the age of six months, there is a regression in the physical and mental formation. The child loses hearing, the ability to swallow. A gaze appears, which is directed to one point. The child becomes lethargic and also only responds to loud sounds. He subsequently goes blind and loses his hearing. There are violations in mental development, the head becomes large. Convulsions are observed, muscles atrophy, paralysis occurs. Death occurs before the age of four.

In the adolescent and adult form of the disease, the symptoms are milder. In this case, there is a violation of speech, muscle spasms occur, gait, fine motor skills and coordination are disturbed, vision is reduced, intelligence and hearing are deteriorating.

Tay's disease? Sachs disease is determined by the presence of a red spot, which is located on the retina opposite the pupil. It can be seen during examination by an ophthalmologist. A red spot on the retina indicates that gangliosides have accumulated in this place in the ganglion cells. After examination with an ophthalmoscope, the doctor prescribes the following:

To date, treatment for the genetic disease of Tay-Sachs has not been developed. Medical care is aimed at relieving symptoms and delaying the development of the disease, at least for a while.

Throughout life, patients are provided palliative care, which provides for feeding through a tube, skin care and more. With seizures, anticonvulsants usually do not help.

Tay's disease? Sachs is incurable. With the best outcome, patients with the childhood form of the disease live up to five years.

Prevention of the disease consists in conducting a survey of married couples for the presence of a mutant gene. If it is found in both spouses, they are advised not to have children. When a woman who is already pregnant is diagnosed, an amniocentesis is prescribed to detect defective genes in the fetus.

Tay-Sachs disease. Rare hereditary disease

Tay-Sachs disease is a disease that is inherited, characterized by very rapid development, damage to the central nervous system and brain of the child.

The disease was first described by the English ophthalmologist Warren Tey and the American neurologist Bernard Sachs in the 19th century. These outstanding scientists have made an invaluable contribution to the study of this disease. Tay-Sachs disease is a fairly rare disease. Certain ethnic groups are predisposed to it. Often this disease affects the population of the French of Quebec and Louisiana in Canada, as well as Jews living in Eastern Europe. In general, the incidence of the disease in the world is 1:250,000.

Tay-Sachs disease occurs in a person who inherits mutant genes from both parents. In the case when only one of the parents is the carrier of the gene, the child may not get sick. But, in turn, it becomes a carrier of the disease in 50% of cases.

If a person has an altered gene, his body stops the production of a certain enzyme - hexosaminidase A, which is responsible for the breakdown of complex natural lipids in cells (gangliosides). It is not possible to remove these substances from the body. Their accumulation leads to blocking of the brain and damage to nerve cells. This is what causes Tay-Sachs disease. Photos of the sick can be seen in this article.

Like other hereditary diseases of newborns, this disease can be diagnosed at an early stage. If parents have a suspicion that their baby is suffering from Tay-Sachs syndrome, then you need to urgently contact an ophthalmologist. After all, the first sign of this terrible disease is a cherry-red spot, which is observed when examining the fundus of a child. The spot occurs due to the accumulation of gangliosides in the cells of the retina.

Then, studies such as a screening test (extensive blood test) and microscopic analysis of neurons are carried out. A screening test shows if the protein hexosaminidase type A is being produced. An analysis of neurons reveals if they have gangliosides.

If parents know in advance that they are carriers of a dangerous gene, then it is also necessary to undergo a screening test, which is performed at 12 weeks of gestation. During the study, blood is taken from the placenta. As a result of the test, it will become clear whether the child has inherited mutant genes from his parents. This test is also carried out in adolescents and adults with the appearance of similar symptoms of the disease and poor heredity.

Development of the disease

A newborn suffering from Tay-Sachs syndrome outwardly looks like all children and seems to be quite healthy. It is a common thing when such rare diseases do not appear immediately, but in the case of the disease in question, only by six months. Up to 6 months, the child behaves in the same way as his peers. That is, he holds his head well, holds objects in his hands, makes some sounds, perhaps begins to crawl.

Since the gangliosides in the cells do not break down, they accumulate in sufficient quantities so that the baby loses the acquired skills. The child does not react to the people around him, his gaze is directed to one point, apathy appears. After a certain period of time, blindness develops. Later, the child's face becomes like a puppet. Usually children with rare diseases that are associated with mental retardation, do not live long. In the case of Tay-Sachs disease, the baby becomes disabled and rarely lives to be 5 years old.

Symptoms of the disease in infants:

• At 3-6 months, the child begins to lose contact with the outside world. This is manifested in the fact that he does not recognize close people, is able to respond only to loud sounds, cannot focus his vision on an object, his eyes twitch, and later his vision worsens.
• At 10 months, the activity of the baby decreases. It becomes difficult for him to move (sitting, crawling, turning over). Vision and hearing are dulled, apathy develops. Head size may increase (macrocephaly).
• After 12 months, the disease is gaining momentum. The mental retardation of the child becomes noticeable, he very quickly begins to lose his hearing, vision, muscle activity worsens, breathing difficulties arise, seizures appear.
• At 18 months, the child completely loses hearing and vision, convulsions, spastic movements, generalized paralysis appear. The pupils do not react to light and are dilated. Further, decerebrate rigidity develops due to brain damage.
• After 24 months, the baby suffers from bronchopneumonia and most often dies before reaching 5 years of age. If the child was able to live longer, he develops a disorder in the coordination in the contractions of different muscle groups (ataxia) and a slowdown in motor skills, which progresses between 2 and 8 years.

Tay-Sachs disease is also represented by other forms.

Juvenile hexosaminidase A deficiency

This form of the disease begins to appear in children between the ages of 2 and 5 years. The disease develops much more slowly than in infants. Therefore, the symptoms of this hereditary disease are not immediately visible. There are mood swings, clumsiness in movements. All this does not particularly attract the attention of adults.

Illness at this age also leads to disability. The child lives up to 15-16 years.

Youthful amorotic idiocy

The disease begins to progress at 6-14 years of age. It has a weak course, but as a result, the sick person acquires blindness, dementia, muscle weakness, possibly paralysis of the limbs. Having lived with this disease even for several years, children die in a state of insanity.

Chronic form of hexosaminidase deficiency

It usually appears in people who have lived for 30 years. The disease in this form has a slow course and, as a rule, proceeds easily. There are mood swings, slurred speech, clumsiness, decreased intelligence, mental abnormalities, muscle weakness, seizures. Chronic Tay-Sachs syndrome was discovered relatively recently, so it is not possible to make predictions for the future. But it is clear that the disease will definitely lead to disability.

Treatment of Tay-Sachs disease

This disease, like all degrees of idiocy, does not yet have a cure. Patients are prescribed supportive care and meticulous care. Usually, drugs prescribed for seizures do not work. Since babies do not have a swallowing reflex and often have to feed them through a tube. The immunity of a sick child is very weak, so it is necessary to treat concomitant diseases. Usually children die due to some kind of viral infection.

Prevention of this disease is the examination of the couple, aimed at identifying mutations in the genes that characterize Tay-Sachs disease. If there are any, then a recommendation should not be made to try to have children.

If your child is sick

At home care you need to learn how to do postural drainage and nasogastric aspiration. You will have to feed the child through a tube, also make sure that there are no bedsores on the skin.

If you have other healthy children, then you need to examine them for the presence of the mutant gene.

Treatment and prevention

Unfortunately, Tay Sachs disease is an incurable disease, but symptomatic therapy is prescribed to alleviate its course, which will make the life of a sick child more comfortable. Depending on the prevailing clinical picture appropriate medications may be prescribed.

As a rule, help is required not only for the child himself, but also for his parents, because the news of such serious illness almost always shocking. In this case, parents are advised to find a support group where they can communicate with people facing a similar problem and receive the necessary psychological support. It is also advisable to consult a geneticist so that each family member can understand and accept the current situation.

Since the disease will gradually progress, the child will need special care. If necessary, you should consult with your doctor about obtaining additional help It is also important to pay a lot of attention to the child, to let him know that his parents love and support him. The life expectancy of such patients can vary over a fairly wide range. With mild symptoms and proper care, some people with amaurotic idiocy live almost as long as healthy people.

As for the prevention of Tay Sachs disease, it consists, first of all, in the competent planning of pregnancy. A married couple who decide to have offspring should be examined by a geneticist to find out if one of the future parents is a carrier of the defective gene. If such a gene was found during the study, the decision whether to have a child or not remains only with the parents.

Description

When an enzyme, such as hexosaminidase A, which is needed to break down certain substances such as fats, is missing or ineffective, they accumulate in lysosomal. This is called abnormal "storage" when there is too much fatty material in the lysosome.

Symptoms associated with Tay Sachs syndrome include:

• exaggerated startle reaction to sudden noises;
• lethargy;
• loss of previously acquired skills (psychomotor regression);
• greatly reduced muscle tone(hypotension).

As the disease progresses, children develop;

• cherry-red spots in the middle layer of the eyes;
• there is a gradual loss of vision and hearing;
• increased muscle stiffness;
• movement restriction progresses (spasticity);
• possible paralysis;
• uncontrolled electrical disorders of the brain (convulsions);
• deterioration of cognitive processes (dementia).

The classic form of Tay-Sachs disease occurs in infancy. This is the most common form and is fatal in early childhood.

There are also adolescent and adult forms of the syndrome, but they are rare. Children with the juvenile form, called subacute, develop symptoms later than those with the infantile form and usually live longer.

The adult form, called late-onset disease, occurs from adolescence up to the middle of 30 years. Symptoms and severity vary.

Tay Sachs syndrome is inherited in an autosomal recessive manner. The disorder results from changes (mutations) in a gene known as HEXA, which regulates the production of the enzyme hexosaminidase A. The HEXA gene is displayed on the long arm (q) of chromosome 15 (15q23-q24). There is no cure, it is aimed at relieving specific symptoms.

Another name for the disease is the GM2 type 1 gangliosidosis type. There are two other related diseases called Sandhoff's disease and hexosaminidase activator deficiency that are indistinguishable from Tay-Sachs syndrome. They can only be differentiated by testing, determining the underlying cause. These two disorders also cause a decrease in hexosaminidase activity, but are caused by changes in different genes. These three disorders are known as GM2 gangliosidoses.

Synonyms

• GM2 gangliosidosis;
• GM2 gangliosidosis type 1;
• Hexoamidase alpha subunit deficiency (option B);
• Hexosaminidase A deficiency;
• Lack of HEXA;
• Sphingolipidosis, Thai-Sachs;

• Infantile Tay-Sachs disease;
• subacute disease;
• late stage.

Affected populations

The disease affects men and women in equal numbers. It is more common among the Jewish people of Ashkenazi origin, that is, among Eastern or Central European origin. Approximately one in 30 Ashkenazi Jews carries the altered gene. In addition, one in 300 people of non-Ashkenazi Jewish heritage is a bearer.

People of Italian, Irish, French, Canadian ancestry have been reported, especially those living in the Cajun community of Louisiana and southeastern Quebec. In the general population, the transfer rate for an altered gene is approximately 1 in 250-300 people.

Late disease occurs less frequently than the infantile form. However, rare forms of the disorder often go unrecognized. They are underrepresented, making it difficult to determine the true incidence of disorders in the general population.

Diagnostics

The diagnosis is confirmed by a thorough clinical evaluation and specialized tests such as blood tests that measure hexosaminidase A levels in the body. Hexosaminidase A is reduced in people with Tay-Sachs disease, absent in the infantile form.

Molecular genetic testing confirms the diagnosis. It detects mutations in the HEXA gene that cause the disorder.

In some cases, it is possible that the diagnosis of Tay-Sachs syndrome may be suspected before birth (prenatally) based on specialized tests such as amniocentesis, chorionic villus sampling (CVS). During an amniocentesis, a sample of the fluid surrounding the developing fetus is taken and CVS obtains a tissue sample from part of the placenta. These samples are studied to determine if hexosaminidase A is present, in a manner that is absent or very low in people with the disease. This is called enzyme analysis.

Blood tests can determine if people are carriers of Tay-Sachs disease (there is one copy of the gene). Relatives must be tested to determine if they are carriers of the disease gene. Couples who are planning to have a baby and are of Jewish ancestry (not just Ashkenazi) are encouraged to get screened before they become pregnant.

There is no specific treatment. It targets specific symptoms and may require a coordinated effort by a team of specialists. Genetic counseling is recommended for affected individuals and their families. Psychosocial support is essential for the whole family.

Due to potential feeding difficulties, nutritional status and proper hydration should be monitored. Nutritional support may be required. In addition, a feeding tube is sometimes needed to help prevent food, liquid, or other foreign material from accidentally entering the lungs (aspiration).

Anticonvulsants are used to treat seizures but may not be effective for everyone. In addition, the type and frequency of seizures often require a change in the type of medication or dosage.

Exploratory Therapy

Work continues on the development of an enzyme replacement therapy(ERT) for Tay-Sachs disease. It consists in replacing the enzyme in individuals who experience a lack or absence of it.

Synthetic versions of the missing enzymes are used to treat people with other lysosomal storage disorders, including Hurler syndrome, Fabry syndrome, and Gaucher disease. However, ERT has not been successful for people with Tay Sachs syndrome. One of the problems is the inability to cross the blood-brain barrier.

• Gene therapy is being explored as a possible approach to the treatment of some lysosomal memory disorders. In gene therapy, a defective gene is replaced with a normal one, allowing the production of an active enzyme that prevents the development and progression of the disease.

Given the constant transmission of the normal gene that produces the active enzyme in all disease foci, this form of therapy is likely to result in a "cure". However, there are currently technical difficulties for the success of this approach.

• Chaperone therapy is also being studied. This type of therapy uses very small molecules that attach to newly created hexosaminidase A enzymes before the mutated ones are destroyed. They direct them to the lysosome, where the enzymes perform their normal function.

Such a molecule can cross the blood-brain barrier. The therapy is in the early stages of research.

• A drug called pyrimethamine has been used as a treatment for Tay-Sachs disease. Affected individuals taking this drug have shown increased hexosaminidase A activity.

However, it did not lead to a noticeable improvement in neurological or mental symptoms. More research is needed to determine if pyrimethamine plays any role in the treatment of this syndrome.

Neurogenetics and hereditary diseases

What do they depend on? From the quality of genetic information inherited from parents and from the conditions of the environment in which a person is located throughout life. Knowing the features of the genome, one can not only diagnose rare diseases, incl. and nervous system, but also with a high degree of probability to determine the characteristics of metabolism and the risks of future diseases, which is important for the correct selection medicines, choice of profession, rational nutrition, etc.

Neurogenetics studies the role of heredity in the occurrence of diseases of the nervous system. Particularly great advances in molecular genetics have been made in the study of progressive degenerations of the brain, neuromuscular diseases, and epileptic syndromes.

Practice of a geneticist in Samara

AT clinical practice For a neurologist to determine the cause of neurological disorders, it is important to use the capabilities of such a laboratory method as the detection of mutations and polymorphisms in the genes responsible for the functioning of the nervous system, muscles, and metabolism in the smallest cell structures, such as the nucleus, mitochondria, lysosomes and pyroxisomes. Dozens of enzymes “work” in these subcellular organelles, on which the energy supply of cells depends. Each enzyme is controlled by a specific gene. The presence of a defect in a gene leads to a blockage of the chemical reaction chain with the accumulation of substances that have not gone through the full cycle of chemical transformations. Accumulation diseases occur. One of them is Fabry disease, in which strokes are frequent even in young people. Drugs that replace a "poorly functioning" enzyme when taken for life (as in the treatment of diabetes) allow a person to be healthy.

In addition, a number neurological disorders occurs with chromosomal pathology, which can be revealed by the study of chromosomes in human blood cells. This study is called karyotyping.

Biochemical methods for identifying the genetic characteristics of bioenergetics and metabolic defects specific to the so-called orphan diseases with neurological manifestations are also of interest to a neurologist. Subtle knowledge of causes and pathogenesis neurological symptoms allows the doctor to make important recommendations for therapy.

By the way, molecular diagnostics and karyotyping are carried out once in a lifetime, since the genotype and set of chromosomes do not change. These analyzes of yours are important even for first-degree relatives, since defects in genes and chromosomes can be inherited.

The effectiveness of neurogenetics on the example of epilepsy

The breadth of the diagnostic and therapeutic possibilities of neurogenetics is well demonstrated by the example of epilepsy. This disease has been known since ancient times and proceeds in the form of convulsive seizures, both partial and generalized tonic-clonic, myoclonic. The linkage of certain forms of epilepsy with mutations of specific genes, point mutations of mitochondrial DNA, and chromosomal disorders has been proven.

There are several reasons for the occurrence of a convulsive syndrome associated with genetics. These are chromosomal diseases: extra 4th or 21st chromosomes, ring 14th chromosome give generalized clonic-tonic, myoclonic convulsions. Ring chromosome 20 results in complex partial and secondary generalized seizures. With a fragile X chromosome, simple partial, atypical absences, generalized convulsions are observed. A deletion (separation of a part) of the 4th or long arm of the 15th chromosome is also manifested by a convulsive syndrome.

These are also hereditary metabolic diseases that occur with convulsive syndrome: phenylketonuria, aciduria, Menkes disease and Wilson-Konovalov disease, non-ketonemic hyperglycinemia, gangliosidosis, adrenoleukodystrophy, galactosialidosis, Krabbe, Tay-Sachs, Sandhoff, Lafora, Gaucher diseases. MELAS syndrome - mitochondrial myeloencephalopathy, lactic acidosis, stroke-like episodes. Syndrome MERRF - myoclonus epilepsy with "torn" red fibers and muscles, detected by histological examination.

More than 500 different forms of progressive muscular dystrophies and neuromuscular syndromes are known to neurogenetics, so the consultation of such a specialist can be very useful for the patient and his family.

In the rehabilitation of patients after acute vascular pathology nervous system (stroke) medications called anticoagulants are used. They prevent the formation of blood clots in the blood vessels. But every 6th European is not sensitive to aspirin and taking this drug will not give the expected effect from it. Another drug that works similar to aspirin is called Warfarin. It was noticed that in one part of the people it causes a good anticoagulant effect, in the other it does not have the expected effect, in the third it causes tissue bleeding. It turned out that various molecular defects in the gene responsible for the metabolism of this drug in the human body lead to this different results. Thus, molecular diagnostics of an individual tendency to thrombosis and testing of genes responsible for the exchange of anticoagulants make it possible to choose an INDIVIDUAL effective therapeutic dose of a drug.

Consultation of a geneticist in Samara

Neurogenetics allows you to most accurately determine the prognosis for the life and health of the patient, as well as the likelihood of children inheriting the patient's hereditary disorders of the nervous system. It is even possible to determine the presence hereditary disease in an unborn child in utero.

We have a geneticist in our clinic.

Tay Sachs disease is a serious hereditary pathology, a childish form of family amaurotic idiocy, arising from damage to the lining of the brain and manifested by progressive mental retardation and severe motor impairment in the child. The pathology is usually characterized by the normal development of children up to the age of six months, then irreversible disorders of the brain function occur, which leads to a high mortality rate in children under five years of age.

Amavrotic idiocy, in particular, Tay Sachs' disease, was first described in the nineteenth century by American neurologists B. Sachs and W. Tay, whose research made an incommensurable contribution to the study of this pathology. It is worth noting that the disease is not common, according to statistics, for two hundred and fifty thousand healthy children, one is born with such disorders.

The reasons

Familial amaurotic idiocy is a rare disease predisposed to by certain ethnic groups. According to existing statistics, the largest number of cases is recorded among residents of French Canada, as well as the Eastern European Jewish population. Thus, among Ashkenazi Jews, the frequency of pathology increases to a ratio of 1:4000.

Tay Sachs disease is characterized by an autosomal recessive mode of inheritance. This means that pathology occurs only in those children who immediately inherit two abnormally altered genes from each of the parents. In cases where the abnormal gene is present in only one parent, the child also becomes a carrier with a 50% probability, although he himself does not become ill.

When abnormal genes are present in the mother and father, there are several options for the development of events in the event of the birth of offspring:

• in 50% of cases, a child is born healthy, but becomes a carrier of a defective gene, thereby putting the health of their future children at risk;
• in 25% of cases, the birth of a child with amaurotic idiocy is possible - this means that he inherited both abnormal genes at once;
• in 25% of cases, absolutely healthy children are born to a married couple who are not carriers of abnormal genes.

The described disease develops as a result of the accumulation of gangliosides in the cells of the nervous system. These substances are special substances that control nervous activity. In the body of a healthy person, gangliosides are continuously synthesized, which are then cleaved. In sick children, the balance between the production and breakdown of gangliosides is disturbed, which is associated with a deficiency of a special enzyme (hexominidase type A), which is responsible for the breakdown of constantly synthesized substances. As a result, gangliosides gradually accumulate in the nervous system, disrupting its functioning and causing irreversible damage.

Forms

Tay Sachs disease in children can occur in two clinical variations:

Manifestations

Amavrotic idiocy does not manifest itself in any way in a newly born baby, since in the first months of life he looks quite healthy and develops adequately. The first symptoms begin to appear at the age of four to six months. You may notice that the child began to react poorly to bright light, to have difficulty focusing on a certain subject, not to respond to noise and what is happening around. When examined by a pediatric ophthalmologist, pathological changes in the retina of the eye are revealed.

Later, after reaching the age of six months, the child becomes much less active than before. He has difficulty turning over or sitting, and begins to see and hear worse. As a result of a strong decrease in motor activity, muscle atrophy and even paralysis often develop, which leads to the fact that the child stops swallowing and breathing on his own. As a rule, during this period, disability occurs. By outward signs the disease can be recognized by the disproportionately large head of the child.

The most active progression of the disease occurs from about ten months of age. Children may have seizures. Unfortunately, with an early onset of the disease, most patients do not live past the age of four to five years.

In those rare cases when amavrotic idiocy develops already in adulthood (from fourteen to thirty years), its manifestations are tolerated by patients a little easier. The clinical picture usually includes disturbances in speech function, gait and coordination of movements. In this case, there is a decrease in intelligence, vision and hearing, periodic muscle spasms occur.

Attack

Tay Sachs disease, among its manifestations, has seizures - sudden outbreaks of abnormal brain activity that have a negative impact on speech, motor, and mental function. The severity of the pathological signs of seizures depends mainly on the frequency of their occurrence and the severity of the course.

If such an attack occurs in a person with amaurotic idiocy, he may fall and begin to convulse with strong muscle contraction and uncontrollable twitching of arms and legs. In other people, the seizure is more like a trance state or hallucinations.

Diagnostics

Thanks to the rapid development modern medicine, amaurotic idiocy can be diagnosed even before the baby is born. During pregnancy, women at risk are recommended to undergo a special screening test, which consists in examining blood taken from the placenta. A blood sample is taken in a procedure called a chorionic biopsy. Another option for such a study is amniocentesis - puncture amniotic sac in order to obtain amniotic fluid for further study in the laboratory.

Based on the results of the screening test, the doctor will be able to conclude whether the hexominidase type A protein is produced in the body of the fetus.

If a disease is suspected after the birth of a child, it must be sent for examination as soon as possible. First of all, you should consult with a pediatric ophthalmologist. The doctor will conduct an examination of the fundus, in which, in the case of Tay Sachs disease, a reddish spot will be detected - an accumulation of gangliosides in the retina. Next, a blood test and microscopic examination of neurons are performed. So, the final diagnosis is made after receiving the results of a genetic test.

Treatment and prevention

Unfortunately, Tay Sachs disease is an incurable disease, but symptomatic therapy is prescribed to alleviate its course, which will make the life of a sick child more comfortable. Depending on the prevailing clinical picture, appropriate medications may be prescribed.

As a rule, help is required not only for the child himself, but also for his parents, because the news of such a serious illness is almost always shocking. In this case, parents are advised to find a support group where they can communicate with people facing a similar problem and receive the necessary psychological support. It is also advisable to consult a geneticist so that each family member can understand and accept the current situation.

Since the disease will gradually progress, the child will need special care. If necessary, you should consult a doctor about obtaining additional help, it is also important to pay a lot of attention to the child, let him know that his parents love and support him. The life expectancy of such patients can vary over a fairly wide range. With mild symptoms and proper care, some people with amaurotic idiocy live almost as long as healthy people.

Tay-Sachs disease (first part)

Tay-Sachs disease (TSD)(also known as GM2 gangliolipidosis, hexosaminidase deficiency, or early infantile amaurotic idiocy ) - this, which causes a progressive deterioration in the mental and physical abilities of the child. The first signs of the disease usually appear around 6 months of age. The disorder usually results in the death of the affected individual around the age of 4 years.

The disease is caused by a specific genetic defect. If a child is affected by BPS, then this means that he has one copy of the defective gene from each parent. The disease manifests itself when nerve cells dangerous amounts of gangliosides accumulate in the brain, resulting in the premature death of these cells. To date, there are no effective drugs or other treatments for this disease. BPS is quite rare compared to other recessive diseases, such as sickle cell anemia, which are more common.

The disease is named after the British ophthalmologist Warren They (who first described a red spot on the retina in 1881) and an American neurologist Bernard Sachs , who worked at Mount Sinai Hospital in New York (he described the cellular changes that occur in BTS and in 1887 noted an increase in the incidence of the disease among Ashkenazi Jews, who are ethnically similar to Eastern Europe).

Studies of the disease that were conducted at the end of the twentieth century showed that Tay-Sachs disease is caused by gene HEXA , which is located on . To date, it has been revealed a large number of HEXA mutations, and new studies provide information on new mutations. These mutations are very common in several populations. The number of carriers among French Canadians (living in the southeast of Quebec) is almost the same as among Ashkenazi Jews, however, the mutations that cause BTS among these ethnic groups are different. Many members of the Cajun ethnic group (who today live in southern Louisiana) carry the same mutations that are most common among Ashkenazi Jews. As already mentioned, these mutations are very rare and do not occur among genetically isolated populations. That is, the disease can only arise from the inheritance of two independent mutations in the HEXA gene.

Classification and symptoms

Tay-Sachs disease is classified according to different forms, depending on the time of onset of neurological symptoms. The form of the disease reflects the variant of the mutation.

Children's form of Tay-Sachs disease.

During the first six months after birth, babies develop normally. But, after the nerve cells accumulate gangliosides and thus stretch, there is a continuous deterioration in the mental and physical abilities of the patient. The child becomes blind, deaf, and cannot swallow. Muscles begin to atrophy, resulting in paralysis. Death usually occurs before the age of four.

Adolescent form of Tay-Sachs disease.

This form of the disease is extremely rare and usually manifests itself in children aged 2 to 10 years. They develop cognitive-motor problems, problems with speech (dysarthria), swallowing (dysphagia), unsteady gait (ataxia), and spasticity occurs. Patients with juvenile BPS usually die between the ages of 5 and 15 years.

The adult form of Tay-Sachs disease (LOTS).

A rare form of the disorder, known as adult-onset Tay-Sachs disease or late-onset Tay-Sachs disease (LOTS), occurs in patients in their 20s and 30s. LOTS is often misdiagnosed and is usually not fatal. It is characterized by gait disturbance and progressive deterioration of neurological function. Symptoms of this form, which occurs in adolescence or early adulthood, are: problems with speech and swallowing, unsteady gait, spasticity, decreased cognitive skills, the onset of mental illness, in particular schizophrenia in the form of psychosis.

Before 1970s and 80s When the molecular nature of the disease became known, the adult and adolescent forms were almost never considered as forms of Tay-Sachs disease. BTS that occurs in adolescence or adulthood is often diagnosed as another neurological disorder, such as Friedreich's ataxia. People affected by BPS in adulthood often use a wheelchair to get around, but many of them live almost full lives, but only if they adapt to the physical and psychiatric complications (which can be controlled with medication).

Journalist Janet Silver Ghent) described the experience of Vera, a girl from a Russian-Jewish family who immigrated to the United States when she was still a child. Twenty years ago, when Vera Pesotchinsky "s) was 14, she had difficulty speaking (her speech became fuzzy, slurred), which is why her parents turned to a speech therapist for help. Later, the girl began to have problems with coordination, sometimes she even fell, besides, Vera could not clearly make certain coordinated movements (for example, she could not peel potatoes). Vera's mother turned to specialists in the field of neurology and psychiatry for advice. And only after 12 years and after a large number of incorrect diagnoses, the girl was finally diagnosed with LOTS.

Despite her disability, Vera graduated from Wellesley College. (Wellesley College) and received her Master of Management (MBA) from Santa Clara University (Santa Clara University). According to J. Gent, Vera lives independently, works daily in the family business, and in addition, she firmly believes that she did not become a victim of BTS, and her example indicates that one can live quite normally with this disease. Faith is an example for all patients with BTS, she speaks to all people affected by this disease and adds motivation to fight for health: “Of course, you can “fall apart” and be sick, but you can also be treated. Do whatever you can to treat the disease, because if I didn't, my situation would be much worse."

Pathophysiology

Tay-Sachs disease occurs due to insufficient activity of the enzyme hexosaminidase A, which catalyzes the biodegradation of a certain class fatty acids known as gangliosides. Hexosaminidase A is a vital hydrolytic enzyme that is found in lysosomes and degrades lipids. When hexosaminidase A stops functioning properly, lipids accumulate in the brain and interfere with normal biological processes. Gangliosides are produced and biodegraded rapidly, early in life, while the brain is developing. Patients and carriers of Tay-Sachs disease can be identified by taking a relatively simple biochemical analysis blood, which determines the activity of hexosaminidase A.

Three proteins are required for the hydrolysis of GM2 ganglioside. Two of these are hexosaminidase A subunits and the third is a small glycolipid transport protein, the GM2 activator protein (GM2A), which acts as a substrate for a specific enzyme cofactor. Deficiency of any of these proteins leads to the accumulation of ganglioside, mainly in the lysosomes of nerve cells. Tay-Sachs disease (together with GM2 gangliosidosis and Sandhoff disease) occurs through genetic mutations inherited from both parents that disable or inhibit the breakdown of these substances. Most BTS mutations, according to scientists, do not affect the functional elements of the protein. Instead, they cause improper accumulation or storage of the enzyme, making intracellular transport impossible.

BPS is an autosomal recessive genetic disorder. This means that if both parents are carriers of the defective gene, then the risk that a newborn child will be sick is 25%. Autosomal genes are chromosomal genes, they are not found on one of the sexes. Each person carries two copies of each autosomal gene, one inherited from each parent. If both parents are carriers of the mutation, then according to the probability of transmitting the disease to the child is 25%. Like all genetic diseases, CTS can occur in any generation, no matter when the mutation first occurred. Although the mutations that cause BTS are quite rare.

Autosomal recessive diseases occur when a child inherits two copies of a defective autosomal gene, that is, when one copy cannot participate in the transcription or expression process as a functional product for the formation of an enzyme.

BPS is caused by a mutation of the HEXA gene, which is located on chromosome 15 and encodes the activity of the alpha subunit of the lysosomal enzyme beta-N-acetylhexoaminidase A. By 2000, more than 100 mutations in the HEXA gene were identified, however, even today the number of known mutations is constantly increasing. These mutations occur as base pair insertions, deletions, splice site mutations, etc. Each of these mutations changes protein product and thus suppresses the activity of the enzyme. Recent demographic studies have shown which mutations arise and spread within small ethnic groups. The following groups formed the basis for the study:

• . Ashkenazi Jews. They are characterized by the insertion of four base pairs in exon 11 (1278insTATC). This results in damage to the reading frame for the HEXA gene. This mutation is most common among Ashkenazi Jews and results in the infantile form of Tay-Sachs disease.
• . Cajun . This ethnic group (whose population lives today in South Louisiana, USA) was separated from the rest of the population for several centuries through linguistic differences. BTS causes the same mutations that are most common among Ashkenazi Jews. The researchers looked at the ancestry of all carriers from several Louisiana families and identified the couple who had their first child with BTS. However, these spouses were not descendants of Jews living in France in the 18th century.
• . French Canadians . This population is characterized by a long sequence deletion which results in the same pathologies that cause the mutations described above (found in Ashkenazi and Cajun Jews). Like the number of Ashkenazi Jews, the number of French-Canadians increased rapidly, from a small group of founders, however, they remained isolated from the rest of the population through geographical, cultural and linguistic barriers. The mutations in the two populations were previously thought to be identical, and the prevalence of BTS in eastern Quebec was due to gene flow. Some scientists then argued that a "sexually active Jewish ancestor" led to a disease-causing mutation among the French-Canadian population. This theory in narrow circles (among genetic scientists) became known as the "Hypothesis of the Jewish Fur Trader". However, subsequent studies have shown that the two mutations have nothing in common.

In the 1960s and early 1970s, when the biochemical basis of Tay-Sachs disease first became known, the mutation sequence that caused any genetic disease could not be pinpointed. Researchers of that era did not yet know how common polymorphism could be. The knowledge of that time reflects precisely "The Jewish Fur Trader Hypothesis" because according to it, only one mutation can spread between populations. Further studies have shown that BTS can cause a large number of mutations, each of which causes the emergence of different forms of the disease. It was BPS that became the first genetic disorder that showed the possibility of such a phenomenon as compound (combined). Such thorough knowledge became available due to the fact that BPS was the first disease for which genetic screening began to be widely used.

The very phenomenon of compound heterozygosity explains various forms disorders, including the occurrence of the adult form of BPS. Potentially, the disease could result from inheriting two distinct mutated copies of the HEXA gene, one from each parent. The classic infantile form of BPS occurs when a child has inherited identically mutated copies of a gene from both parents, the dysfunction of which causes complete inactivation of the process of cleavage (biodegradation) of gangliosides. The adult form of HEXA arises through the inheritance of various mutations, and although a person may be heterozygous, he can inherit two different HEXA gene mutations, the combined effect of which leads to inactivation, change or decrease in the activity of the desired enzyme. If a patient has at least one copy of the HEXA gene that allows hexosaminidase to perform its functions, then the result is the emergence of an adult form of BPS.

In heterozygous carriers, i.e. in individuals who have inherited only one mutant, the level of enzyme activity is also somewhat reduced, but they do not show any signs or symptoms of the disease. Bruce Korf explains why carriers of recessive mutations usually do not develop symptoms of a genetic disease:

“The biochemical basis for the dominance of wild-type over mutant alleles in congenital metabolic diseases can be understood by studying how proteins function. Enzymes are proteins that catalyze chemical reactions, i.e. only a small amount of substance is needed for the normal implementation of the catalysis reaction. If in homozygous individuals, the gene encoding the activity of the enzyme is mutated, then this leads to a decrease in the activity of the enzyme or to its absence in the body altogether, i.e. this person will exhibit an abnormal phenotype. But in heterozygous individuals, the level of enzyme activity is at least 50% of normal level, through the expression (action) of wild-type alleles. This is usually sufficient to prevent violation ».

Diagnostics

Improvement of the developed testing methods allowed neuropathologists to diagnose Tay-Sachs disease and others much more accurately. neurological diseases. However, sometimes Tay-Sachs disease is misdiagnosed because doctors are not sure if it is a type of genetic disease that is common among Ashkenazi Jews.

Patients with this disease have a "cherry" spot of the macula, which is easy for the doctor to identify with an ophthalmoscope on the retina. This patch is an area of ​​the retina that is enlarged by the accumulation of gangliosides in the surrounding retinal ganglion cells (these are the neurons of the central nervous system). Thus, only the cherry-red macula is the part of the retina that provides normal vision. Microscopic analysis of neurons shows that these cells are stretched (loaded with gangliosides) due to excessive accumulation of gangliosides. Without the use of molecular diagnostic methods, only the cherry spot of the macula is feature and a sign in the diagnosis of all gangliosidoses.

Unlike some other lysosomal storage diseases (eg, Gaucher disease, Sandhoff disease), hepatosplenomegaly is not hallmark Tay-Sachs disease.

Journalist Amanda Pazornik (Pazornik) describes the experience of the Arbogast family: "Peyton was a beautiful girl - but she could not sit, roll over, play with her toys. Moreover, Peyton's symptoms progressively worsened. Loud, incomprehensible noise frightened her. The inability to coordinate the movements of the muscles of the mouth and tongue led to she could choke on meals and cause excessive salivation.” Since neither of Peyton's parents was Jewish, her doctors did not suspect that she had Tay-Sachs disease until she was 10 years old. months, that's when an ophthalmologist noticed a macular cherry spot in her eyes.Peyton died in 2006 at the age of 3.5.This is a characteristic course of the disease.The child becomes increasingly "lazy" due to a violation of neurodegenerative development and shows an excessive reflex from hyperacusis. The sick person becomes increasingly lethargic and has trouble eating Spasticity and movement disorders may become noticeable. is most common among Ashkenazi Jews.

Prevention

BTS screening is carried out in two possible ways:

- Carrier detection test. During the test, it is determined whether healthy man carrier of one copy of the mutation. Many people who want to be tested for carrier identification are at-risk couples who are planning to start a family. Some people and couples want to be screened because they know an ancestor or family member has a genetic disorder.

Tay Sachs disease, amaurotic idiocy, is a rare, neurodegenerative disorder in which a deficiency of an enzyme (hexosaminidase A) leads to the excessive accumulation of certain fats (lipids) known as gangliosides in the brain and nerve cells.

This abnormal accumulation of gangliosides leads to progressive dysfunction of the central nervous system.

It is classified as a lysosomal disease. Lysosomes are the main cells of digestion. Lysosome enzymes break down or "digest" nutrients, including some complex carbohydrates and fats.

When an enzyme, such as hexosaminidase A, which is needed to break down certain substances such as fats, is missing or ineffective, they accumulate in lysosomal. This is called abnormal "storage" when there is too much fatty material in the lysosome.

Symptoms associated with Tay Sachs syndrome include:

• exaggerated startle reaction to sudden noises;
• lethargy;
• loss of previously acquired skills (psychomotor regression);
• severely reduced muscle tone (hypotension).

As the disease progresses, children develop;

• cherry-red spots in the middle layer of the eyes;
• there is a gradual loss of vision and hearing;
• increased muscle stiffness;
• movement restriction progresses (spasticity);
• possible paralysis;
• uncontrolled electrical disorders of the brain (convulsions);
• deterioration of cognitive processes (dementia).

The classic form of Tay-Sachs disease occurs in infancy. This is the most common form, and is fatal in early childhood.

There are also adolescent and adult forms of the syndrome, but they are rare. Children with the juvenile form, called subacute, develop symptoms later than those with the infantile form and usually live longer.

The adult form, called late onset, occurs between adolescence and mid-30s. Symptoms and severity vary.

Tay Sachs syndrome is inherited in an autosomal recessive manner. The disorder is the result of changes (mutations) in a gene known as HEXA, which regulates the production of the enzyme hexosaminidase A. Gene HEXA displayed on the long arm (q) of chromosome 15 (15q23-q24). There is no cure, it is aimed at relieving specific symptoms.

Another name for the disease is the GM2 type 1 gangliosidosis type. There are two other related diseases called Sandhoff's disease and hexosaminidase activator deficiency that are indistinguishable from Tay-Sachs syndrome.

They can only be differentiated by testing, determining the underlying cause. These two disorders also cause a decrease in hexosaminidase activity, but are caused by changes in different genes. These three disorders are known as GM2 gangliosidoses.

Synonyms

• GM2 gangliosidosis;
• GM2 gangliosidosis type 1;
• Hexoamidase alpha subunit deficiency (option B);
• Hexosaminidase A deficiency;
• Lack of HEXA;
• Sphingolipidosis, Thai-Sachs;

stages

• Infantile Tay-Sachs disease;
• subacute disease;
• late stage.

signs

Tay-Sachs disease is subdivided into the classic or infantile form, juvenile, and adult or late onset. Individuals in the infantile stage develop symptoms between three and five months of age. In the late form, symptoms are visible from adolescence to 30 years of age.

Infantile form

The infantile form is characterized by almost total absence activity of the enzyme hexosaminidase A. The disorder progresses rapidly, leading to significant mental and physical deterioration.

Babies may appear perfectly healthy at birth. Initial symptoms, usually develop between 3 to 6 months, include:

• muscle weakness;
• twitching (myoclonic jerks);
• an exaggerated startle reaction, such as when there is a sudden or unexpected noise.