Tay Sachs syndrome is a 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 Thay and the American neurologist Bernard Sachs in the 19th century. These outstanding scientists have made invaluable contributions to the research of this disease. Tay-Sachs disease is a fairly rare disease. Certain ethnic groups are predisposed to it. This disease often affects the French population of Quebec and Louisiana in Canada, as well as Jews living in Eastern Europe. In general, the worldwide incidence of the disease is 1:250,000.

The main causes of Tay-Sachs disease

This disease is considered very rare, and certain ethnic groups are predominantly susceptible to its development. This disease most often affects the French population, which lives in Canadian Quebec and Louisiana, as well as the Jewish population in Eastern Europe. Moreover, among Ashkenazi Jews, such a pathology occurs in one person in 4000. This disease is inherited only in an autosomal recessive manner, which means that the disease can occur in a child who has simultaneously inherited two defective genes, for example, the first gene from the mother and the second from the father. If there is a gene defect in one of his biological parents, the child will not end up getting sick, but with a 50% chance of becoming a carrier of this defective gene, future offspring are ultimately at risk.

When two parents have a defective gene, then with a 25% probability the children will not be carriers of the gene, but will also be born completely healthy. And with a 50% chance the child will also be a carrier of this gene and will also be born healthy. In the third case, with a 25% probability, the child may inherit two affected genes at once, but will be born with Tay-Sachs disease. The mechanism for the development of this pathology is the slow accumulation of gangliosides in the nervous system, that is, substances that are responsible for the normal functioning of all nerve cells. In a strong, healthy body, gangliosides are always synthesized, therefore they are constantly broken down, and enzyme systems are responsible for the normal maintenance of balance between breakdown and synthesis. All sick children have a damaged gene, which is responsible for the complete synthesis of hexosaminidase enzymes from type A. A child’s body with a congenital deficiency of this enzyme is not yet able to constantly break down all the forming and all accumulating fatty substances, that is, gangliosides, which are quickly deposited in the brain, which blocks the functioning of nerve cells, but this leads to the most severe symptoms.

Tay-Sachs disease: symptoms, causes, treatment, prevention | 2020

Tay-Sachs disease is a rare, fatal disease that is most often diagnosed in children around 6 months of age.

There is no cure for this disease, but scientists have a good idea of ​​what causes it, how it worsens, and how to use genetic testing to detect it early in pregnancy.

Researchers are working to make advances in gene therapy or bone marrow transplants that they hope will make it possible to treat Tay-Sachs in the future.

What causes Tai-Sachs?

Defects in a gene called HEXA cause Tay-Sachs. (You can think of genes as the “coding” that your parents pass on to you. Genes are found in your cells, and they determine the traits of your body, from the color of your eyes to your blood type to your gender.)

Most people have two healthy versions of this HEXA gene, which instructs your body to make an enzyme (a type of protein) known as Hex-A. This enzyme prevents the accumulation of a fatty substance called GM2 ganglioside in the brain and spinal cord.

Some people have only one normal copy of the gene and still produce enough Hex-A protein to keep their brain and spinal cord healthy. But children born with Tay-Sachs disease have inherited a mutated copy of the gene from both parents, so they don't produce the Hex-A protein. This is what makes them so sick.

Over time, GM2 ganglioside accumulates in their nervous system and begins to cause harm.

symptoms

A baby born from Tay-Sachs grows normally until 3-6 months.

Around this time, parents may notice that their baby's development begins to slow and muscles become weaker. Gradually, the disease causes more symptoms in children, including:

• Loss of motor skills such as rolling over, sitting and crawling
• Very strong reaction to loud noises
• Trouble focusing on objects or following them with your eyes
• Cherry-red spots, which can be detected during eye examination, in the eyes

By age 2, most children with Tay-Sachs begin to have more serious problems. These may include:

• Trouble swallowing and breathing that gets worse
• Seizures
• Loss of mental function, hearing and vision
• Paralysis

At age 3, children with Tay-Sachs syndrome have few visible changes, but the nervous system continues to decline, often leading to death by age 5.

Thai-Sachs Management

There is no cure for this disease. But there are ways to manage symptoms and make life easier for children with Tai-Sachs and their families.

Some of the specialists, treatments and programs you might consider include:

• Speech language pathologists. They can help your baby maintain his sucking and swallowing reflex, and can also help you know when it's time to think about feeding your baby.
• Neurologists. These professionals can help you manage your child's seizures with medications.
• Respiratory health. Specialists such as pediatricians and pulmonologists (doctors who treat lungs and breathing problems) can advise parents on ways to reduce the likelihood of lung infections in their child.
• Play and stimulation. You can help your baby interact with the world through music, scents, and textures.
• Massages. They can relax your child.
• Palliative and hospice care. These programs help manage the quality of life of children with Thai Sachs and their families.

Who gets Tai-Sax?

The disease is extremely rare. In the general population, only about 1 in every 112,000 live births is affected.

Anyone can be a carrier of the HEXA mutation, which means they have only one defective copy of the HEXA gene.

However, the likelihood of inheriting the disease is higher in certain groups due to a higher proportion of carriers. Approximately 1 in every 27 Jews in the United States is a carrier. Non-Jewish French Canadians living along the St. Lawrence River in Canada and in the Cahoon community of Louisiana also have a higher incidence of Tai-Sax.

If both parents are carriers of Tay-Sachs disease, there is a 25% chance that any child they have will contract the disease.

Can this be prevented?

You can take a blood test that analyzes your genes or the levels of the Hex-A protein in your blood to determine if you are a carrier.

If two people planning to have children find out they are both carriers, a genetic counselor can help them consider options to reduce their chances of having a child with Tay-Sachs.

Tai-Sachs later in life

There is an even rarer type of Tay-Sachs called “late-onset” or “adult-onset.” It can be difficult to diagnose.

Like the version of the disease that affects children, Tay-Sachs, which begins later in life, is caused by mutations of the HEXA gene. Symptoms may begin to appear anywhere from adolescence to adulthood.

Early symptoms often include clumsiness, balance problems, and muscle weakness in the legs. People with it may also have mental health problems.

With this form of the disease, life expectancy and severity of symptoms vary from case to case. Late onset of Tay-Sachs does not always shorten life expectancy.

Source: https://ru.medicineofme.com/30-what-is-tay-sachs-disease-89165

Main symptoms of Tay-Sachs disease

The disease usually affects children around six months of age. Even at the beginning of the development of the disease, the baby loses contact with the entire world around him, and he also develops a very intent gaze, directed only at one point, the baby becomes apathetic, and he also reacts only to loud sounds. After all this, the baby loses his acquired skills, that is, he stops crawling, he experiences mental retardation, and then the child begins to go blind. All muscle functions, that is, the ability to drink, eat, pronounce sounds, move, are significantly reduced, and can even reach complete loss, and the head becomes disproportionately large. Already in the later stages of the development of the disease, somewhere between 1 and 2 years of his life, the child may experience seizures. And in this case, the child dies before reaching the age of five.

At the age of 3 to 6 months, the baby has difficulty focusing on objects, eyes twitch, visual perception deteriorates, and unreasonable reproduction of very loud sounds is observed. At the age of 6 to 10 months, a child develops, that is, muscle tone decreases, he becomes less active, his vision and hearing deteriorate significantly, and his head greatly increases in size, his motor skills become dull, and as a result, it is difficult for the child to roll over, sit. After 10 months, the baby has mental retardation and develops.

Tay Sachs disease: diagnostic procedures and treatment regimen

Tay Sachs disease is a hereditary disease characterized by rapid development and damage to the child’s brain and central nervous system.

This disease was first described in the 19th century. The disease acquired its name from two scientists who contributed to the study of this disease - the Englishman Warren Tay and the American Bernard Sachs.

This disease is more typical for certain ethnic groups. It mainly affects Jews born in Eastern Europe and French people living in Canada, Quebec and Louisiana.

The incidence of the disease in the world is 1 in 250 thousand people.

What causes this disease?

Tay Sachs disease develops only if the parents together are carriers of a mutant gene, and the child inherits two genes with a defect. If one of the parents is a carrier of the gene, then the probability of the child getting sick is almost zero. But, most likely, he will also be a carrier of this disease.

What happens in the body during this disease? The reason for the development of the disease is that due to the presence of an altered gene in a person, his body ceases to produce a certain enzyme - hexosaminidase, which is also responsible for the breakdown of complex natural lipids - gangliosides in cells.

In a healthy body, there is a constant process of synthesis and breakdown of gangliosides, and this process is very precise and any failure leads to irreversible consequences. As a result of a genetic failure, gangliosides are not broken down, but accumulate in the baby’s body, causing damage to the brain and the entire nervous system.

Unfortunately, it is impossible to remove them from the body, and the person develops certain symptoms of the disease.

What is the clinical picture of this disease?

At birth, a baby diagnosed with Tay Sachs syndrome appears completely healthy. The first signs of the disease appear at six months. Until this age, a completely healthy-looking baby is developing as expected: holding his head, cooing, crawling.

But, progressing and accumulating gangliosides in the body, the child gradually begins to lose the acquired skills. The baby stops reacting to the environment, his gaze is directed to one point, and apathy develops. Over time, mental development stops and blindness develops.

Over time, the child's face becomes like a doll's. The result of the disease is disability and early mortality.

Let's look at the symptoms as the child gets older:

• By 6 months, the child begins to lose contact with the outside world, ceases to recognize his family, reacts only to very loud sounds, cannot focus on a hanging toy, his eyes tremble and his vision deteriorates.
• By 10 months, the baby becomes less active, motor functions are impaired: it is difficult for the baby to sit, roll over and crawl. Hearing and vision become dull, the baby becomes apathetic.
• After 1 year of life, the disease progresses very quickly. The child's mental retardation is noticeable; he quickly loses vision and hearing, muscle activity deteriorates, breathing difficulties appear, and seizures begin.

It is important! Children who develop symptoms of Tay Sachs disease in infancy survive until they are five years old.

How is the disease diagnosed?

Today, medicine has come a long way, and Tay Sachs disease can be diagnosed both in an infant and even before his birth.

If you suspect that your baby is developing Tay Sachs syndrome, you should first contact an ophthalmologist.

The first sign of the disease can be diagnosed by the fundus of the eye. If the child is sick, you can see a cherry-red spot. This is characteristic of the disease - the accumulation of gangliosides in the cells of the retina.

Further examination includes:

• extensive blood test - screening - test;
• as well as microscopic analysis of neurons.

Screening test - shows whether the child’s body produces a protein - hexazaminidase A or not. This test is performed for any form of the disease.

Microscopic analysis of neurons is the detection of gangliosides in neurons. With a large number of them, neurons become elongated.

If the parents belong to one of the ethnic groups or there were genetic diseases in the family, it is best to undergo screening - a test at 10-12 weeks of pregnancy. The test will show whether the fetus has inherited the mutated genes from both parents or not. The test is taken using a blood sample from the placenta.

What is the treatment for Tay Sachs disease?

Unfortunately, medicine has not yet found a way to treat this disease. It comes down to supportive therapy and careful care only. Most anticonvulsants do not have a beneficial effect.

Since babies do not have a swallowing reflex, feeding through a tube is required. The therapy also includes treatment of current diseases due to the child’s weakened immune system.

The cause of death is usually a viral infection.

Prevention of the disease comes down to examining a married couple for the absence of mutations in the genes for Tay Sachs disease. If a defective gene is detected in both spouses, the recommendation is not to have children.

Source: https://VashNevrolog.ru/nasledstvennye-zabolevaniya/bolezn-teya-saksa-diagnosticheskie-procedury-i-sxema-lecheniya.html

Basic treatment for Tay-Sachs disease

Unfortunately, this disease cannot be cured, and with good care, almost all children with the childhood form of this disease can only live up to five years. Throughout life, to alleviate the symptoms present, sick children receive palliative care, that is, feeding through a tube, which includes nutritional supplements, and careful care of their delicate skin is provided. In most cases, anticonvulsants are simply powerless against. Prevention of this disease includes mandatory screening of married couples for the presence of the gene for this disease. When both spouses are found to have this gene, they are not recommended to have children at all. If a woman is already pregnant at the time of testing this gene, amniocentesis is performed to identify the defective gene in the child.

Tay-Sachs disease

(
GM 2 gangliosidosis, early childhood amaurotic idiocy
) is a rare hereditary disease with an autosomal recessive pattern of inheritance that affects the central nervous system (spinal cord, brain, and meningeal membranes).
Belongs to the group of lysosomal storage diseases. Named after British ophthalmologist Warren Tay ( 1843-1928
) and American neurologist Bernard Sachs (
1858-1944
), who first described the disease independently in 1881 and 1887, respectively.

Tay Sachs disease is a hereditary disease

Tay Sachs disease is a serious hereditary pathology, a childhood form of familial amaurotic idiocy, which appears in connection with damage to the lining of the brain and is observed in the form of progressive mental retardation with obvious impairment of motor skills in children.

With this pathology, children can develop normally until 6 months of age, after which irreversible disorders of brain function begin, which lead to high mortality among children under 5 years of age

Causes

Tay Sachs disease is a fairly rare disease to which certain ethnic groups are predisposed. Existing statistics confirm that people living in French Canada, as well as the Jewish population of Eastern Europe, are most susceptible to this disease.

Thus, Ashkenazi Jews have a frequency of pathology that has increased to a ratio of 1:4000.

Amaurotic idiocy is characterized by autosomal recessive inheritance, therefore, the pathology can manifest itself only in those children who receive abnormal genes from both parents at once. When the abnormal gene is present in only one parent, the child will not get the disease, but has a 50% chance of becoming a carrier.

Photo. Girl with Tay Sachs disease

If the abnormal gene is present in both parents, then several outcomes are possible for the offspring born:

• There is a 50% chance that the child will be healthy, but will become a carrier of an abnormal gene, which is a risk for the next generation of children;
• There is a 25% chance that amaurotic idiocy will manifest itself in a born child, which indicates the inheritance of both abnormal genes;
• the probability of giving birth to a completely healthy child without the manifestation of abnormal genes, who will not be a carrier of the disease, is 25%.

Amaurotic idiocy manifests itself in the process of accumulation of gangliosides in nerve cells. This substance is a special element of the central nervous system that controls its activity. The bodies of healthy people regularly synthesize this substance, which is then broken down.

People with the disease have an imbalance between the synthesis and breakdown of gangliosides, which is caused by a deficiency of special enzymes that are responsible for the breakdown of regularly produced substances. Such a disorder causes the regular accumulation of gangliosides in the nervous system, causing disruption of its functions and irreversible destruction.

Symptoms

At the moment of birth of a child diagnosed with Tay Sachs syndrome, he looks like a completely healthy baby. Symptoms of the disease begin to appear by the 6th month.

Before this age, the child develops correctly. But as gangliosides accumulate in the body, regression of the acquired skills begins. The child’s reaction to his surroundings worsens, his gaze is more often directed at one point, and an apathetic state is observed. After some time, blindness begins to develop, and intellectual development stops.

Symptoms as the child gets older:

1. At 6 months of age, the baby begins to lose contact with the environment, does not recognize his parents, the reaction appears only to fairly loud sounds, the gaze does not focus on hanging toys, and vision deteriorates.
2. A 10-month-old baby loses activity, motor functions are impaired: the child has difficulty sitting, rolling over, and crawling.
   Auditory and visual functions deteriorate, and apathy appears.
3. After a year of life, the disease progresses quite quickly. The child looks mentally retarded, quickly loses visual and auditory functions, muscle activity decreases significantly, breathing becomes difficult, and seizures appear.

Infants who develop Tay Sachs disease survive until they are 5 years old.

The disease is manifested by attacks of sudden abnormal brain activity, which has a detrimental effect on speech, motor activity and mental function. The severity of seizures depends on the severity of the disease and the frequency of seizures.

Amovratic idiocy causes seizures, due to which the patient may fall, convulsions begin with strong muscle contractions, uncontrolled twitching of the arms and legs. Other people have a seizure and go into a hallucinogenic or trance-like state.

Late onset of symptoms

There is a late onset of symptoms of this disease, which is one of two forms of the disease.

Juvenile hexosaminidase type A deficiency

This form can appear in children aged 2-5 years. The disease progresses more slowly than the clinical form. In such cases, the onset of symptoms is noticed at a later age. Sudden mood swings and clumsy movements do not attract attention.

While later symptoms are more obvious:

• the child has progressive muscle weakness;
• convulsive twitching;
• thinking abilities are impaired, speech becomes slurred.

Such symptoms lead to disability and death at the age of 15-16 years.

Chronic form of hexazaminidase deficiency

A similar form appears by the age of 30. The disease is mild, progresses slowly, and occurs in a relatively mild form: sudden changes in mood are possible, clumsiness is present, slurred speech occurs, mental deviations occur, the level of intelligence drops, muscle weakness progresses, and seizures appear.

This form of the disease was discovered not so long ago, so it is impossible to make a forecast for the future at the moment. It is known that the disease will also cause disability.

Diagnostics

At the moment, medicine has made great progress, which makes it possible to detect Tay Sachs disease not only in a baby, but also before his birth.

If you suspect Tay Sachs disease, you should immediately contact an ophthalmologist, since the first signs appear on the fundus in the form of a cherry-red spot. The spot is an accumulation of gangliosides in the retinal cells.

Further examinations are required, which include:

1. Screening is a test that shows the presence of production of a protein in the child’s body - hexazaminidase A. The test is carried out for any form of the disease.
2. Neuronal microanalysis, which will reveal ganglioside in nerve cells. When the content of gangliosides is high, the neuron becomes elongated. In cases where parents are representatives of an ethnic risk group or are carriers of the disease, a screening test is recommended to be carried out during the 10-12th week of pregnancy. This makes it possible to identify a hereditary disease. The analysis is performed on a placental blood sample.

Treatment

Amaurotic idiocy is an incurable disease, however, it is possible to alleviate its course by carrying out symptomatic therapy to create more comfortable conditions for the child’s life. Medicines are prescribed depending on the clinical picture.

Most often, not only the baby needs help, but also the parents, since the news of such an illness leads to a state of shock.

Parents are recommended to become members of specialized groups where they can feel the support of people who find themselves in a similar situation.

In addition, consultation with a geneticist is recommended so that each family member can analyze and accept the disease.

As the disease gradually progresses, the child needs special care, increased attention, as well as love and support from the parents. The patient's life expectancy can vary significantly depending on the form and symptoms. There are examples when a sick person, with proper care, lived a long, full life.

Prevention

Prevention of the disease lies primarily in a well-planned pregnancy. Spouses must undergo genetic testing to identify the defective gene. If such a gene is detected, the decision to conceive remains with the spouses.

Family history

Family history allows the doctor to find out about the presence of sick blood relatives or carriers of the disease among them. This approach allows us to determine the degree of risk for the unborn child.

Blood relatives who will help determine the possibility of manifestation of the disease:

• immediate family, including parents, sisters, brothers and children;
• secondary relatives, including parents' sisters and brothers, nephews, grandparents;
• cousins.

Sometimes the family history is very complex, which is influenced by the following factors:

• close relationship of the patient with a relative who has been diagnosed with a gene leading to the disease;
• number of relatives with a similar disease.

Genetic counseling

Counseling involves explanations from a specialist to help a person deal with the dangerous consequences of a genetic disease.

Consultation with a geneticist includes:

• explaining to parents the mechanism of transmission of the disease from them to the baby;
• studying the complications that will be caused by a genetic disease;
• consideration of possible procedures to detect genetic diseases before pregnancy;
• discussion of the results and the likelihood of parents having children with a genetic disorder;
• providing assistance in understanding the risk of genetic diseases;
• studying issues that will help with further treatment of the disease;
• Assisting the patient or spouse in the decision-making process regarding testing for genetic diseases.

The pathology in question cannot necessarily become a death sentence if you approach the problem of symptom management and patient care wisely. Despite the fact that life expectancy with such an illness is often short, parents should try to make it as joyful as possible for the baby.

Source: https://prodepressiju.ru/narusheniya-intellekta/bolezn-teya-saksa-nasledstvennoe-zab.html

Classification

There are three forms of Tay-Sachs disease:

• Child form
  - six months after birth, children experience a progressive deterioration in physical abilities and mental abilities: blindness, deafness, and loss of the ability to swallow are observed. As a result of muscle atrophy, paralysis develops. Death occurs before the age of 3-4 years.
• Adolescent form
  - motor-cognitive problems,
  dysphagia
  (impaired swallowing),
  dysarthria
  (speech disorders),
  ataxia
  (unsteadiness of gait), spasticity (contractures and paralysis) develop. Death occurs before the age of 15-16 years.
• Adult form
  - occurs between the ages of 25 and 30 years. It is characterized by symptoms of progressive deterioration of neurological functions: impaired and unsteady gait, swallowing and speech disorders, decreased cognitive skills, spasticity, and the development of schizophrenia in the form of psychosis.

Clinical picture

Newborns with this hereditary disease develop normally in the first months of life. However, at the age of about six months, regression occurs in mental and physical development. The child loses vision, hearing, and the ability to swallow. Convulsions appear. The muscles atrophy and paralysis occurs. Death occurs before the age of 4 years.

Etiology and incidence of Tay-Sachs disease

. (MIM #272800), early childhood gangliosidosis GM2, is a panethnic autosomal recessive disorder of ganglioside breakdown caused by hexosaminidase A deficiency (see Chapter 12). In addition to the severe form in early childhood, hexosaminidase A deficiency causes a mild form of the disease with onset in adolescence or adulthood.

Incidence of hexosaminidase A deficiency

varies widely among different populations; The incidence of Tay-Sachs disease in North America ranges from 1 in 3,600 births among Ashkenazi Jews to 1 in 360,000 among non-Ashkenazi Jews. French Canadians, Cajuns in Louisiana, and Amish in Pennsylvania have comparable rates of Tay-Sachs disease to Ashkenazi Jews. The increased carrier frequency in these four populations is a consequence of genetic drift, although a heterozygote advantage cannot be ruled out.

Pathogenesis of Tay-Sachs disease

Gangliosides

- ceramide oligosaccharides, present in the surface membranes of all cells, but most of all in brain cells. Gangliosides are concentrated in the surface membranes of neurons, especially in axons and dendrites. They function as receptors for various glycoprotein hormones and bacterial toxins and are involved in cell differentiation and intercellular interaction.

Hexosaminidase A

- a lysosomal enzyme consisting of two subunits. The a-subunit is encoded by the HEXA gene on chromosome 15, and the beta subunit is encoded by the HEXB gene on chromosome 5. In the presence of an activator protein, hexosaminidase A removes the terminal N-acetylgalactosamine from the GM2 ganglioside.

Mutations of a-subunit genes

or activator protein cause the accumulation of GM2 in lysosomes and, thereby, the early childhood, late childhood or adult type of Tay-Sachs disease. [Mutation of the α subunit causes Sandhoff disease (MIM no. 268800)].

Mechanism of how GM2 ganglioside

causes neuronal death is not fully defined, although, similar to Gaucher disease, toxic byproducts of GM2 ganglioside may cause neuropathology. The level of residual hexosaminidase A activity is inversely proportional to the severity of the disease.

Patients with early childhood form of GM2 gangliosidosis

have two pathological alleles leading to a complete absence of hexosaminidase activity. Patients with juvenile-onset or adult-onset forms of GM2 gangliosidosis are usually compound heterozygotes for a complete loss of function allele and an allele with little residual hexosaminidase A activity.

Phenotype and development of Tay-Sachs disease

Early childhood type of gangliosidosis GM2

characterized by neurological deterioration beginning at 3–6 months of age and leading to death by 2–4 years. Typically, motor development stops or begins to regress by 8–10 months of life, and the inability to move independently develops during the second year of life. Vision loss begins in the first year of life and progresses rapidly; it is almost always associated with a “cherry-red” spot (“pit”) on fundus examination.

Seizures usually begin at the end of the first year of life and become progressively more severe. Further deterioration in the second year of life ends with decerebrate rigidity, difficulty swallowing, severe convulsions and, finally, a vegetative state.

Gangliosidosis GM2

with late childhood onset is detected at 2-4 years of life, it is characterized by neurological symptoms, starting with ataxia and incoordination. By the end of the first decade, most patients have spasticity and seizures; By 10–15 years, most develop decerebrate rigidity and a vegetative state, with death usually occurring in the second decade of life. Decreased vision is noted, but there may be no “cherry pit” in the fundus; Optic atrophy and retinitis pigmentosa often appear late in the course of the disease.

Adult type GM2 gangliosidosis

has marked clinical variability (progressive dystonia, spinocerebellar degeneration, motor neuron pathology or psychiatric disorders). Up to 40% of patients have progressive psychiatric manifestations without psychosis. Vision is rarely affected, and ophthalmologic examination findings are usually normal.

Features of phenotypic manifestations of Tay-Sachs disease

: Age of onset: early childhood to adulthood Neurodegeneration “Cherry Pit” Psychosis

Treatment of Tay-Sachs disease

Diagnosis of GM2 gangliosidosis

diagnosed based on the detection of both absent or almost absent hexosaminidase A activity in blood serum or leukocytes, and normal or increased hexosaminidase B activity. For diagnosis, you can also use the analysis of mutations in the HEXA gene, but usually it is performed only to clarify transport carriage and prenatal diagnostics

Tay-Sachs disease

currently an incurable disease; therefore, treatment focuses on symptom management and palliative care. Almost all patients require pharmacological treatment for seizures. The psychiatric manifestations of patients with adult-onset GM2 gangliosidosis are usually refractory to standard antipsychotic or antidepressant medications; The most effective are lithium drugs and electroconvulsive therapy.

Risks of inheriting Tay-Sachs disease

For potential parents without GM2 gangliosidosis

family history, the empirical risk of having a child with CM2 gangliosidosis depends on the frequency of the disease in their ethnic groups. For most North Americans, the empirical risk of being a carrier is approximately 1 in 250 to 300, but for Ashkenazi Jews, the empirical risk of being a carrier is approximately 1 in 30. For a couple in which both parents are carriers, the risk of having a child with GM2 gangliosidosis is 1/4.

Prenatal diagnosis

is based on the identification of mutations in the HEXA gene or on the determination of hexosaminidase A deficiency in fetal tissues, for example, chorionic villi or amniocytes. To effectively identify an affected fetus using HEXA mutation analysis, it is usually necessary that the mutations causing GM2 gangliosidosis in the family are already known.

Population screening

high-risk carrier status and subsequent preventive measures reduced the incidence of Tay-Sachs disease among Ashkenazi Jews by almost 90%. Traditionally, such screening is performed by determining the activity of hexosaminidase A in blood serum with an artificial substrate.

This sensitive method

, however, is unable to distinguish between pathological mutations and pseudo-deficiencies (reduced breakdown of artificial substrate, but normal breakdown of natural substrate); therefore, carriage is usually confirmed by molecular HEXA testing. Two pseudodeficiency alleles and more than 70 pathological mutations were found in the HEXA gene.

Among Ashkenazi Jews

, positive according to the results of enzyme screening, 2% are heterozygous for the pseudodeficiency allele, and 95-98% are heterozygous for one of three pathological mutations, two cause the early childhood form, one causes the adult form of GM2 gangliosidosis. In contrast, among the remaining North Americans positive by enzyme screening, 35% are heterozygous for pseudodeficiency alleles.

Example of Tay-Sachs disease

. A married couple, both Ashekenazi Jews, were referred to a genetics clinic to assess the risk of having a child with Tay-Sachs disease. My wife's sister died of Tay-Sachs disease in childhood. The husband's paternal uncle is in a psychiatric hospital, but his diagnosis is unknown. Both husband and wife refused carrier screening for Tay-Sachs disease in adolescence.

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

This disease is a hereditary disease of the nervous system and is quite rare.

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

Tay-Sachs disease

Tay-Sachs disease is a serious hereditary pathology, a childhood form of familial amaurotic idiocy, resulting 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 normal development of children up to six months of age, then irreversible disorders of brain function occur, which causes high mortality in children under five years of age.

This disease is a hereditary disease of the nervous system and is quite rare. The disease got its name in honor of the two doctors who discovered it - Warren Tay (an ophthalmologist from Britain) and Bernard Sachs (a neurologist from America). Let's look at what kind of disease this is, what causes, symptoms and treatment methods are prescribed.

What it is?

Tay-Sachs disease is a hereditary disease that occurs extremely rarely, has autosomal recessive inheritance and is characterized by damage to the central nervous system.

The disease was first described by the English ophthalmologist Warren Thay and the American neurologist Bernard Sachs in the 19th century. These outstanding scientists have made invaluable contributions to the research of this disease.

Tay-Sachs disease is a fairly rare disease. Certain ethnic groups are predisposed to it. This disease often affects the French population of Quebec and Louisiana in Canada, as well as Jews living in Eastern Europe.

In general, the worldwide incidence of the disease is 1:250,000.

Reasons for appearance

For a long time, doctors could not answer the question of what causes Tay-Sachs disease. The causes of the pathology became known only in the middle of the twentieth century, when ideas about genetics were formed.

Studies have shown that the disease develops as a result of a mutation in the HEXA gene, which is located on the 15th chromosome. The disease is a type of GM2 gangliosidosis, a genetic pathology associated with a deficiency or decreased activity of hexosaminidase.

Amaurotic idiocy occurs as a result of a decrease in the activity of hexazaminidase A or a deficiency of this enzyme.

Tay-Sachs disease is inherited in an autosomal recessive manner. This suggests that only a child who has inherited two defective genes at once - the first from the mother and the other from the father - can get sick.

If only one of the biological parents has the defective gene, the child will not get sick, but with a 50% chance of becoming a carrier of the defective gene, thereby putting their future offspring at risk.

What can happen if both parents have the defective gene:

• There is a 25% chance that the child will not be a carrier of this gene and will be born completely healthy.
• 50% of the child will be a carrier of this gene and will be born completely healthy
• There is a 25% chance that the child will inherit two affected genes and will be born with Tay-Sachs disease

Pathogenesis

The basis for the development of the disease is the absence or insufficient activity of hexosaminidase A, a lysosomal enzyme that catalyzes the biodegradation of macromolecules of gangliosides, oligosaccharides, glycosaminoglycans and glycolipids.

Gangliosides are a type of fatty acid, lipid components of the membranes of neurons and glial cells.

They ensure the activity of nerve cells: they influence the speed and intensity of neurotransmission, the conduction of nerve impulses, the distribution and storage of information, and memory formation.

Normally, gangliosides are produced, perform their functions and are quickly broken down in a multi-step reaction involving enzymes. For the hydrolysis of these complex lipids, three components are required: the alpha and beta subunits of hexosaminidase A, and the GM2A activator protein.

If alpha-hexosaminidase A is deficient, the biodegradation process slows down or becomes completely impossible. Gangliosides accumulate in lysosomes of brain and spinal cord cells, leading to their dysfunction and death.

Classification

Tay-Sachs disease (amaurotic idiocy) comes in three forms:

• childhood – manifests itself at six months of age and is accompanied by a progressive decline in mental and physical capabilities;
• teenage – motor-cognitive disorders, dysarthria, dysphagia, ataxia, spasticity appear;
• adult – is a rare form, manifests itself at 25–30 years of age and is accompanied by a progressive decline in neurological functions.

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.

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

1. deficiency of hexosaminidase type A in a chronic form - with this type of pathology, its manifestations can appear both at the younger age of three to five years, and upon reaching the age of thirty. This form of pathology is characterized by a relatively mild course with disturbances in fine motor skills, speech apparatus, intelligence and muscle spasms. It is worth noting that the described type of amaurotic idiocy was discovered not so long ago; it is impossible to make clear predictions regarding its course, however, it can be argued that the most likely outcome of the pathology will be disability and subsequent death of the patient;
2. Deficiency of hexosaminidase type A in the juvenile form - manifests itself at a very early age and does not progress as quickly as the classic form of Tay Sachs disease. However, the death of an incurable disease is inevitable; adequate therapy will only help delay the death of the patient.

Symptoms of Tay-Sachs disease

The main manifestations of the pathology are:

• developmental delay,
• loss of acquired skills,
• loss of hearing
• loss of vision,
• amyotrophy,
• seizures,
• paralysis,
• inability to swallow.

Attack

Tay Sachs disease, among its manifestations, has seizures - sudden outbreaks of abnormal brain activity that have a negative effect 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 convulse with strong muscle contractions and uncontrollable jerking of the arms and legs. For other people, the seizure is more like a trance state or hallucination.

Tay-Sachs disease - MRI image

Symptoms of the disease in infants:

1. At 3-6 months, the child begins to lose contact with the outside world. This manifests itself in the fact that he does not recognize close people, is able to react only to loud sounds, cannot focus his vision on an object, his eyes tremble, and later his vision deteriorates.
2. At 10 months, the baby's activity decreases.
   It becomes difficult for him to move (sit, crawl, roll over). Vision and hearing become dull, apathy develops. The size of the head may increase (macrocephaly).
3. After 12 months the disease gains momentum.
   The mental retardation of the child becomes noticeable, he very quickly begins to lose hearing, vision, muscle activity worsens, breathing difficulties arise, and seizures appear.
4. At 18 months, the child is completely deprived of hearing and vision, convulsions, spastic movements, and generalized paralysis appear.
   The pupils do not respond to light and are dilated. Next, decerebrate rigidity develops due to brain damage.
5. 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 of coordination in the contractions of different muscle groups (ataxia) and a slowdown in motor skills, which progresses between 2 and 8 years.

Late onset of symptoms

There is a late onset of symptoms of this disease, which is one of two forms of Tay-Sachs disease:

Juvenile hexosaminidase type A deficiency

What it is? This form can appear in children aged 2-5 years. The disease progresses more slowly than the clinical form. In such cases, the onset of symptoms is noticed at a later age. Sudden mood swings and clumsy movements do not attract attention.

While later symptoms are more obvious:

• the child has progressive muscle weakness;
• convulsive twitching;
• thinking abilities are impaired, speech becomes slurred.

Such symptoms lead to disability and death at the age of 15-16 years.

Chronic form of hexazaminidase deficiency

A similar form appears by the age of 30. The disease is mild, progresses slowly, and occurs in a relatively mild form: sudden changes in mood are possible, clumsiness is present, slurred speech occurs, mental deviations occur, the level of intelligence drops, muscle weakness progresses, and seizures appear.

This form of the disease was discovered not so long ago, so it is impossible to make a forecast for the future at the moment. It is known that the disease will also cause disability.

Complications

Symptoms of BTS include epileptic seizures, which are the result of sudden bursts of abnormal bioelectrical activity in the brain. With their high frequency, physical and mental degradation occurs faster. During an attack, patients fall and convulse, which is accompanied by a high risk of suffocation (retraction of the tongue root) and fatal injuries.

The main complication of the acute infantile form of the disease is infections: in children, the functions of the immune system are reduced, damage to the respiratory system is recurrent and extremely severe. A common cause of death is pneumonia.

Diagnostics

Doctors are not always able to make the correct diagnosis when it comes to such a rare pathology as Tay-Sachs disease. The symptoms, genetics and treatment of the disease are being actively studied by specialists.

Regardless of the form of the disease, there are several diagnostic procedures that are performed if its presence is suspected. One of them is the determination of the activity of the enzyme hexosaminidase in blood serum, leukocytes or fibroblasts.

In patients with Tay-Sachs disease, the activity of hexosaminidase B is always below normal, the enzyme hexosaminidase A is practically absent or its activity is significantly below normal.

Tay-Sachs disease is identified by the presence of a red spot that is located on the retina opposite the pupil. It can be noticed when examined by an ophthalmologist. A red spot on the retina indicates that gangliosides have accumulated in the ganglion cells at this location. After examination using an ophthalmoscope, the doctor prescribes:

• detailed blood test;
• microscopic analysis of neurons;
• screening.

Treatment

Unfortunately, Tay-Sachs disease cannot be cured. Even with the best care, almost all children with childhood forms of the disease survive to a maximum of five years.

• Throughout life, to alleviate the symptoms present, patients receive palliative care (tube feeding with the inclusion of nutrient supplements, careful skin care, etc.).
• Anticonvulsants are most often powerless against seizures.
• Babies are fed through a tube because they do not have a swallowing reflex.
• In addition, therapy is carried out for emerging diseases, because the patient’s body is weakened and immunity is reduced.

Source: https://travmatolog.net/bolezn-teya-saksa/

Development of the disease depending on age

There are three forms of the disease:

• a childhood form
  of amaurotic familial idiocy, in which babies 6 months after birth experience a sharp deterioration in physical and mental health (blindness and deafness develop rapidly, the child loses the ability to swallow);
• adolescent form
  , in which there is also a violation of swallowing, severe speech disorders, instability in gait, and paralysis;
• adult form
  , which develops between the ages of 25 and 30 years. To the symptoms listed above is added schizophrenia, which occurs in the form of psychosis.

Causes of the disease

The causes of the disease lie in disorders at the genetic level

, which occur in ganglioside metabolism. 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 a ratio of 1 in 250,000. This disease mainly affects the population of ethnic groups, for example, the French, whose place of residence is Canada.

Jews from Eastern Europe are also susceptible to the disease, with a higher incidence rate of 1 in 4,000 people.

This disease develops in a child who has inherited 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 dad and mom in equal amounts. If one or both chromosomes of a pair are damaged, then a genetic disease is said to occur. In people with Tay-Sachs disease, both chromosomes in a pair are defective.

This disorder is called a disease with autosomal recessive inheritance. If one of the parents has a defective gene, the baby will be healthy, but with a 50% chance of being a carrier, which jeopardizes the health of his heirs in the future. If both parents have a gene with a defect, there are three possible developments.

There is a 25% chance that a child will be born healthy and will not be a carrier of the gene. In 50% of cases, the baby will be a carrier of the defective gene, but will be born healthy. In 25% of cases, the baby may get two genes with a defect, and he will be born with Tay-Sachs disease.

Risk factors

The driving force for the development of this disease is the gradual accumulation of gangliosides in the nervous system - substances that affect the normal functioning of 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 are then deposited in the brain.

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

Main symptoms

The pathology is diagnosed in babies at the age of approximately six months, since until four to five months the child develops quite normally, like all children of this age.

initial stage

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 exclusively to loud and sharp sounds. Even when the baby looks completely healthy, parents and loved ones often notice that the child shudders sharply with his whole body when exposed to loud auditory stimulation.

A complex of disorders manifested by increased fatigue, sleep disturbances, and mood instability are called by one term -.

Hereditary Friedreich's ataxia causes serious damage to the nervous system - causes, symptoms and pathologies.

Development of the disease

The second stage of the disease is regression in the child’s development: 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 vision, and often hearing.

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

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

Signs of the disease in adults

The adult form is very rare and occurs in patients between 20 and 30 years of age. It is usually not fatal.

The disease manifests itself in gait disturbances and rapid deterioration of neurological functions. An adult can live with this disease for 10 to 15 years after diagnosis.

Diagnosis of the disease

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

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

Changes are also observed in the optic nerve nipple: it atrophies.

It is impossible to cure, it is necessary to support

Treatment for Tay-Sachs disease must begin before the onset of neurological signs. Blood and plasma transfusions are used.

There are no medications or specific methods that cure Tay-Sachs disease.

The doctor prescribes only medications that can support liver function, as well as various vitamins and anticonvulsants.

The latter are often ineffective against the seizures that occur with this disease. Medical care consists of simply alleviating the symptoms of the disease, but if we are talking about a late form, then it is to delay 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 undergo testing for the presence of the gene for this disease, if there were cases of Tay-Sachs disease in the family of at least one of the spouses.

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

.

For this purpose, amniotic fluid obtained by puncture of the amniotic membrane is subjected to laboratory testing. If the defective gene is found, the pregnancy must be terminated.

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

To conduct the study, doctors take blood from the placenta to find out whether the unborn baby has inherited mutant genes.

Future parents need to take responsibility for their own health and the health of their future children and follow all doctor’s recommendations.

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

• Deafness
• Swallowing disorder
• Breathing problems
• Impaired concentration
• Loud noise intolerance
• Mental retardation
• Retarded physical development
• Paralysis
• Eye twitching
• Loss of vision
• Sitting problems
• Decreased motor skills
• Decreased vision
• Decreased muscle tone
• Reduced activity
• Difficulty turning over from stomach to back
• Enlargement of the head
• Deterioration of visual perception

Tay-Sachs disease is a genetic pathology that affects the brain and nervous system. This includes the spinal cord and meninges. In the first six months of a child's life, his development is normal. Then disruptions in brain activity begin. Newborn children are diagnosed with gangliosidosis gm1. Such patients die after 3 - 4 years. This pathology has a second name – gm2 gangliosidosis.

Prognosis and prevention

If amaurotic idiocy occurs in early childhood or in adolescence, the prognosis is most often unfavorable. At this stage of life, the disease mainly provokes the death of the patient. There is hope for survival in those with the late version of the disorder, in which symptoms develop at a slower pace.

To prevent the development of Tay-Sachs syndrome in a child, before conception it is recommended to undergo an examination aimed at identifying defective genetics. When conducting diagnostics, the possibility of transmission of the anomaly from family members of future parents, including distant relatives, is also taken into account. If exposure to BTS is confirmed, the decision about the upcoming pregnancy is made independently. At the same time, the potential father and mother are informed in detail about the possible risks and complications of the disease.

To rule out Tay-Sachs disease, some Jewish communities take extreme measures. A special Committee for the Prevention of Genetic Disorders has been created, conducting anonymous screening studies. For couples who are found to be carriers of amaurotic idiocy, starting a family is not recommended.

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Etiology

With Tay-Sachs disease, there is only one reason - the development of the disease in a baby is possible only in one case, when both parents have a mutated gene, which will be passed on from father and mother to the child. But if only one parent has the mutated gene, then the risk of developing the pathology in the child is zero - the baby will be a carrier.

The cause of Tay-Sachs disease is as follows: the body stops producing a special enzyme, hexosaminidase, because it contains an altered gene. The breakdown of lipids (gangliosides) in the cells of the body is also disrupted.

In a healthy body, this process occurs with great precision. If any failure occurs, then irreversible complications will arise. In the event of a genetic failure, the breakdown of gangliosides does not occur: they gradually accumulate in the body, and this leads to a malfunction of the brain and central nervous system. It is impossible to remove them from the body, so a person develops characteristic symptoms of Tay-Sachs disease.

Causes of the disease

Tay-Sachs disease occurs in a person who inherits mutant genes from both parents. If only one of the parents is a 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 brain function and damage to nerve cells. This is what causes Tay-Sachs disease. Photos of the sick can be seen in this article.

Classification

There are three forms of this pathology:

With the latter form we can say that the person will be disabled. Life expectancy will depend on many factors.

Symptoms

For each period of a child's life up to one year, Tay-Sachs disease exhibits symptoms of a different nature.

Age up to six months:

• it is difficult for the baby to concentrate on one subject;
• decreased visual perception;
• eye twitching;
• repetition of very loud sounds.

From six months to ten months:

• decreased activity;
• low muscle tone;
• the baby sits poorly, rolls over, motor skills decrease;
• vision deteriorates;
• hearing decreases to the point of deafness;
• head size increases.

After ten months:

• blindness develops;
• mental retardation;
• paralysis;
• breathing and swallowing problems.

The first symptom of Tay-Sachs disease is the baby's sharp sensitivity to loud sounds. It will also be accompanied by an unusual reaction. The child begins to experience delayed physical and mental development. Lost interest in the environment and close relatives. Acquired skills disappear. Over time, blindness begins. Muscle atrophy occurs. In the later stages of pathology development, seizures occur.

After ten months, gm2 gangliosidosis begins to progress rapidly. Seizures begin - flashes of electrical brain activity that occur for unknown reasons. They affect the functioning of the musculoskeletal system, visual images are perceived incorrectly. Speech and psychological perception of reality are impaired. In each case, the degree of damage is individual. For example, some are convulsing on the floor, others are standing motionless. Some patients may smell or see images that are not visible to a healthy person.

In the final stages of the pathology, some patients are fed through a tube. In this state, there is practically nothing that can be done to help him. The only thing is that it requires careful care, as well as treatment for emerging infectious diseases. Death occurs due to or other infection.

Symptoms of amaurotic idiocy

Tay-Sachs symptoms appear as they grow older, a newborn is not much different from a healthy child, the first signs are detected after 6 months. Over six months, the level of gangliosides increases significantly, which provokes the manifestation of the clinical picture:

• at six months there is a problem with focusing the gaze and a decrease in visual acuity;
• at ten months, activity and hearing decrease, motor activity is impaired, the child loses the ability to sit down and hold the body in this position, he loses the ability to crawl and roll over;
• after a year of life, the pathology rapidly progresses, mental retardation, problems with vision and hearing are noted, motor activity and muscle tone decrease, and the respiratory process becomes difficult.

The following symptoms are typical for the disease:

• changes in brain activity;
• problems with the musculoskeletal system;
• convulsive seizures.

Children with BTS very rarely survive the age of five - the prognosis for this type of anomaly is negative.

Late symptoms of amaurotic idiocy

Amaurotic idiocy Tay-Sachs disease of the juvenile variety can appear after two or five years. In this case, progression is slow and may include:

• frequent emotional swings;
• clumsiness in gestures and movement;
• convulsive twitching;
• muscle abnormalities;
• speech defects.

This form of BTS is complicated by disability and death; patients very rarely survive the age of sixteen.

Chronic form of amaurotic idiocy

Tay-Sachs idiocy of the chronic type begins to appear at the age of twenty. It occurs with mild symptoms and does not lead to death. A person has:

• slurred statements;
• emotional changes;
• clumsiness in movements;
• mental disorders;
• low intellectual abilities;
• muscle weakness.

The attacks are periodic. Patients with BTS lose the ability to move independently - only with the help of a wheelchair. If timely therapy is carried out, then such patients have every chance of a long, full life with minor changes and restrictions.

Diagnostics

If symptoms appear, you should consult your doctor. He will refer the patient for examination.

Diagnosis of Tay–Sachs disease is as follows:

• An examination is carried out by an ophthalmologist. When checking the organs of vision, when this pathology develops, the doctor identifies a cherry-red spot on the fundus.
• A skin biopsy is prescribed.
• Blood analysis.

Before the baby is born, Tay-Sachs disease is diagnosed during an analysis of the amniotic fluid. They take it by puncturing the amniotic sac.

Pathogenesis of the disease

The anomaly occurs due to insufficient activity of hexosaminidase-A. It is a lysosomal enzyme that triggers the production of macromolecules such as gangliosides, olisaccharides, glycosaminoglycans and glycolipids.

The pathogenesis of Tay-Sachs disease is relatively simple. Gangliosides belong to fatty acids; they are responsible for metabolic processes in neurons and membrane cells. These components influence the degree of activity of nerve connections, the speed of information transmission and the redirection of nerve impulses. The level of information learned and the ability to remember it depend on them.

During normal development, gangliosides are produced in the required quantities. Having fulfilled the function assigned to them, they split. When a malfunction occurs in the genome associated with excessive accumulation of these substances, an excess of gangliosides occurs in the brain and spinal cord, which leads to their dysfunction and death.

Classification

Initially, three types of BTS are distinguished, which have different clinical pictures with variable symptoms.

1. The infant form (from 3 to 6 months) is detected as the baby grows, when a lack of visual response and focusing of the gaze begins to appear. By ten months, the musculoskeletal system is almost completely suppressed, and idiocy begins to rapidly progress. At 17–18 months, the baby lacks hearing and vision, develops paralysis and decerebrate rigidity. Most often, children die due to complications associated with infectious lesions. In this case, an ophthalmological examination of the fundus will show: a cherry-red molecular stain. Exodiagnostics reveal a complete absence of hexosaminidase-A.
2. The juvenile form (from 3 to 6 years) progresses more slowly than the infant form. The first signs are associated with the appearance of dysarthria, turning into mutism. The anomaly is aggravated by spastic paresis and cerebellar ataxia. The late stage is characterized by convulsive syndrome, urinary incontinence, and psycho-emotional excitability. During ENMG, denervation and atrophy of muscle tissue are detected in children. The prognosis is unfavorable.
3. The late form occurs with symptoms of motor neuron disease, when the upper neurons of the brain are affected, followed by the involvement of the spinal cord in this process. The patient completely loses the ability to move independently. The course of the pathology is slow. The prognosis is favorable, a person lives to be 60–70 years old.

The latter type of deviation is rare in the medical literature; the exact age of appearance of the corresponding signs is difficult to indicate.