Tay Sachs disease is a hereditary disease. Tay Sachs disease: diagnostic procedures and treatment regimen Tay Sachs Idiocy
Tay-Sachs disease is a genetic disorder that causes damage to 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 failures in work of brain activity begin. Newborns are diagnosed with gangliosidosis gm1. Such patients die in 3-4 years. This pathology has a second name - gangliosidosis gm2.
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 that will pass from father and mother to the child. But if only one parent has a mutated gene, then the risk of developing a pathology in a child is zero - the baby will be a carrier.
The cause of Tay-Sachs disease is this: the production of a special enzyme, hexosaminidase, stops in the body, because an altered gene is present in it. The breakdown of lipids (gangliosides) in the cells of the body is also disrupted.
In a healthy body, this process takes place with great accuracy. If any failure occurs, then irreversible complications will arise. With 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 the characteristic symptoms of Tay-Sachs disease.
Classification
There are three forms of this pathology:
- Children's. Upon reaching the child of six months, a constant deterioration in physical health begins. In addition, there are mental difficulties. Vision falls, deafness appears, the swallowing reflex disappears. Muscles begin to atrophy, and eventually paralysis occurs. Life expectancy with this form of pathology is 4 years. These babies are diagnosed with gm1 gangliosidosis or generalized gangliosidosis.
- Teenage. Problems with motor skills and mental performance begin. The process of swallowing is disturbed, speech is distorted, an uncertain gait appears. Increased muscle tone in the limbs. Life expectancy is 16 years.
- Adult. Appears closer to 30 years. Deterioration of neurological functions and gait begins. The characteristic symptoms of this form are problems with speech, swallowing, gait. Decreased mental performance, increased muscle tone. It starts to show up.
The latter form can be said to be an invalid. Life expectancy will depend on many factors.
Symptoms
For each period of a child's life up to a year, Tay-Sachs disease shows symptoms of a different nature.
Age up to six months:
- it is difficult for a child to concentrate on one subject;
- decreased visual perception;
- eye twitching;
- repetition of very loud sounds.
Six months to ten months:
- decrease in activity;
- low muscle tone;
- the baby does not sit well, rolls over, motor skills are reduced;
- vision deteriorates;
- hearing is reduced up to deafness;
- head size increases.
After ten months:
- blindness develops;
- mental retardation;
- paralysis;
- respiratory failure, swallowing.
The first symptom of Tay-Sachs disease is called the baby's sharp sensitivity to loud sounds. It will also be accompanied by an unusual reaction. The child begins to delay physical and mental development. Loss of interest in the environment and close relatives. Acquired skills disappear. Over time, blindness begins. Muscle atrophy occurs. In the later stages of the development of pathology, seizures occur.
After ten months, gm2 gangliosidosis begins to progress rapidly. Seizures begin - flashes of electrical brain activity, occur after unknown reasons. They affect the functioning of the musculoskeletal system, visual images are perceived incorrectly. Speech and psychological perception of reality are disturbed. In each case, the degree of damage is individual. For example, some convulse on the floor, others stand motionless. Some patients can smell or see images that are not visible to a healthy person.
In the last stages of the pathology, some patients are fed through a tube. In this state, it is almost impossible to help him with anything. The only thing is that it requires careful care, as well as therapy for emerging infectious diseases. Death occurs due to or another infection.
Diagnostics
If symptoms appear, you should consult your doctor. He will refer the patient for examination.
Diagnosis of Tay-Sachs disease is as follows:
- Examination by an ophthalmologist. During the examination of the organs of vision, with the development of this pathology, the doctor reveals a cherry-red spot on the fundus.
- A skin biopsy is ordered.
- Blood analysis.
Before the baby is born, Tay-Sachs disease is diagnosed in him during the analysis of the amniotic fluid. It is taken by puncturing the fetal bladder.
Treatment
To date, scientists have not yet identified treatments for Tay-Sachs disease. All treatment is aimed at maintaining the patient and caring for him. In practice, it has been noted that the prescribed anticonvulsants do not have the expected effect. Feeding babies is carried out through a tube, because they do not have a swallowing reflex.
In addition, the therapy of emerging diseases is carried out, because the patient's body is weakened and immunity is reduced.
Prevention
Prevention of Tay-Sachs disease is as follows:
- A married couple must undergo a special examination before conception. Based on its results, the presence or absence of mutant genes is established. If they were found in both parents, then it is recommended not to have children.
- If pregnancy has occurred and the parents know that they are carriers of the mutated gene, then a screening test is performed at the twelfth week. For this, blood is taken from the placenta. According to its results, the doctor reveals the presence or absence of such a deviation in the fetus.
Future parents should take care of their health and especially the health of their unborn baby. Therefore, it is necessary to follow all the advice and recommendations of the doctor. Conducting a survey before conception will enable the child to be healthy.
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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 got its name from two scientists who contributed to the study of this disease - the Englishman Warren Tey 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 per 250 thousand people.
What provokes this disease?
Tay Sachs disease develops only if the parents together are carriers of the mutant gene, and the child inherits two genes with a defect. If the carrier of the gene is one of the parents, then the probability of getting sick in a child is almost zero. But, most likely, he will also be a carrier of this disease.
What happens in this disease in the body? 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, as well as the one responsible for the breakdown of complex natural lipids - gangliosides in cells. In a healthy organism, there is an invariable process of synthesis and breakdown of gangliosides, and this process is very precise and any failure of it leads to irreversible consequences. As a result of a genetic failure, gangliosides do not break 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 a person develops certain symptoms of the disease.
What is the clinical picture of this disease?
At birth, a baby diagnosed with Tay Sachs syndrome looks completely healthy. The first signs of the disease appear at six months. Until this age, a completely healthy-looking baby develops as expected: holds its head, cooing, crawling. But, progressing and accumulating gangliosides in the body, the child gradually begins to lose the acquired skills. The kid stops responding to the environment, his gaze rushes to one point, apathy develops. After a while, mental development stops and blindness develops. Over time, the child's face becomes like a doll. The result of the disease is disability and early death.
Consider the symptoms as the child grows:
- By 6 months, the child begins to lose contact with the outside world, ceases to recognize relatives, reacts only to very loud sounds, cannot focus on a hanging toy, his eyes twitch and vision deteriorates.
- By 10 months, the baby becomes less active, motor functions: Difficulty for baby to sit, roll over and crawl. Hearing and vision are dulled, the baby becomes apathetic.
- After 1 year of life, the disease progresses very quickly. His mental retardation is noticeable in the child, he quickly loses his sight, hearing, muscle activity worsens, breathing difficulties appear, seizures begin.
It is important! Children who develop symptoms of Tay Sachs disease in infancy live to the age of five.
Late onset of symptoms
Sometimes the symptoms of the disease do not appear immediately. There are two more forms of this disease.
Juvenile hexasaminidase type A deficiency
This form of severe illness appears in children from 2 to 5 years. The development of the disease is slow, in contrast to the clinical form. In this case, the symptoms may not be noticed immediately. Mood swings and some clumsiness in movement do not attract much attention. In addition, at this age, whims are normal.
But later symptoms attract attention:
- the child develops muscle weakness;
- convulsive twitches;
- impaired thinking abilities and slurred speech.
Unfortunately, all these signs lead to disability. Death occurs around 15-16 years of age.
Chronic form of hexasaminidase deficiency
It usually occurs in people in their 30s. The course of the disease is weak. It develops gradually, proceeds relatively easily: mood swings, clumsiness can be noticeable, slurred speech appears, mental abnormalities, intelligence decreases, muscle weakness, seizures occur. Due to the fact that this particular form of the disease was discovered recently, it is impossible to make a forecast for the future. Only one thing is clear that this form of the disease will inevitably lead to disability. Life expectancy depends on many factors.
How is the disease diagnosed?
Today, medicine has gone far ahead, and Tay Sachs disease can be diagnosed both in an infant and even before birth.
If there is a suspicion that the baby has Tay Sachs syndrome, first of all, you need to contact an ophthalmologist.
The first sign of the disease can be diagnosed by the fundus. If the child is sick, then you can see a cherry-red spot. This characteristic of the disease is the accumulation of gangliosides in the cells of the retina.
Further testing includes:
- extensive blood test - screening - test;
- as well as microscopic analysis of neurons.
Screening test - shows whether a protein is produced in the child's body - hexasaminidase A or not. This test is carried out with any form of the disease.
Microscopic analysis of neurons is the detection of gangliosides in neurons. With a large number of 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 analysis is taken using a blood sample from the placenta. 
What is the treatment for Tay Sachs disease?
Unfortunately, medicine has not yet found a cure for this disease. It comes down to supportive care and meticulous care. Most anticonvulsants do not give a positive effect. Since babies do not have a swallowing reflex, feeding through a tube is required. The therapy also includes the treatment of current diseases due to the weakened immunity of the child. Usually the cause of death is a viral infection.
Prevention of the disease comes down to examining a married couple for the absence of a mutation in the genes for Tay Sachs disease. If a defective gene is found in both spouses, a recommendation should not be made to have children.
is a genetic disease characterized by deficiency of the enzyme hexosaminidase A, accumulation of lipoid macromolecules in neurons, dysfunction of the brain and spinal cord. It is manifested by the degradation of physical skills and mental functions: the disintegration of the swallowing reflex, speech and voluntary movements, loss of hearing and vision, and a decrease in intelligence. Seizures, muscle atrophy, paralysis, dementia develop. Specific diagnostic methods - ophthalmoscopy of the fundus, the study of the amount of hexosaminidase in the blood and neurons. Treatment is palliative, aimed at relieving symptoms.
ICD-10
E75.0 Gangliosidosis-GM2
General information
Synonyms for Tay-Sachs disease (TSD) are GM2 gangliosidosis, Tay-Sachs idiocy, early infantile amaurotic idiocy. It is one of the variants of lysosomal storage diseases. It is named after two doctors - US neurologist Bernard Sachs and UK ophthalmologist Warren Tey. In the 1980s, they first published independent descriptions of this pathology. Its prevalence is extremely low; in the general population, the average frequency of carriers of a recessive altered gene is about 0.3%. Epidemiological indicators are highest in the group of Ashkenazi Jews (carrying the mutation is determined in 3%), as well as in French Canadians and Cajuns. The peak incidence occurs at the age of six months to 2 years, less often the symptoms debut in adolescents and adults.
The reasons
Metabolic disorders that form the basis of the disease are caused by a mutation of the HEXA gene, which is located on the long arm of chromosome 15. It encodes the alpha subunit of the lysosome enzyme beta-N-acetylhexosaminidase A. Tay-Sachs disease is inherited in an autosomal recessive manner - for the onset of symptoms, the presence of two mutated genes on the chromosome is necessary. The risk of illness in a child exists only if both spouses are carriers of the mutation and is 25%. Thus, pathology can manifest itself in any generation, regardless of when the mutation occurred. Carriage can remain hidden for a long time - in this case, the dominant "healthy" gene is able to provide the body with the production of the enzyme by 50% or more, which is sufficient for the normal course of biochemical reactions.
By the early 2000s, more than 100 different mutations in the HEXA genes were identified: insertions in base pairs, deletions of base pairs, splice site mutations, point mutations, and other variants of changes in the structure of the gene. Each of these mutations in a certain way affects the structure of the enzyme and suppresses its activity. A variety of mutations in a pair of genes - compound heterozygosity - determines the presence of several forms of the disease. Equally mutated genes in alleles cause complete inactivation of ganglioside catabolism. Inheritance of different (not identical) mutations in a pair of genes is more often manifested by a decrease in enzyme activity, rather than complete inactivation.
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 acids, lipid components of the membranes of neurons and glial cells. They ensure the activity of nerve cells: they affect the speed and intensity of neurotransmission, the conduction of nerve impulses, the distribution and storage of information, and the formation of memory. Normally, gangliosides are produced, perform their functions, and are rapidly degraded in a multi-step reaction involving enzymes. Three components are required for the hydrolysis of these complex lipids: the alpha and beta subunits of hexosaminidase A, and the GM2A activator protein. With a lack of alpha-hexosaminidase A, the biodegradation process slows down or becomes completely impossible. Gangliosides accumulate in the lysosomes of cells of the brain and spinal cord, leading to their dysfunction and death.
Classification
Depending on the characteristics of the genetic defect, the preservation of hexosaminidase functions, the disease has a rapidly progressive or slowly progressive course, manifests itself in early childhood, adolescence, or adulthood. According to these characteristics, 3 forms of the disease have been identified:
- Acute infantile. The most common. Symptoms appear several months after birth. The course is progressive. Motor skills quickly deteriorate, blindness, deafness, paralysis develop. Death occurs within 2-3 years.
- Late juvenile. It is extremely rare. The first manifestations are found in the interval from 2 to 10 years. Acquired complex skills gradually disintegrate - walking, speaking, writing. The average life expectancy of patients is 15 years.
- Chronic adult. The scientific literature describes isolated cases of this form, which begins at 25-30 years. Characterized by impaired speech, voluntary motor acts, mental disorders (psychosis). The prognosis of lethality is unknown.
Symptoms of Tay-Sachs disease
The clinical picture of the disease reflects the processes of damage to the central nervous system. In the infantile form, the first symptoms become noticeable by 3-5 months, before that the development is normal: the child holds his head, rolls over on his stomach and back, gurgles, smiles at the sight of an adult, establishes visual contact. By 6 months, interest in the outside world decreases. The kid looks away for a long time, is apathetic, inactive, sensitive to loud sounds, bright light. He ceases to recognize close people, with difficulty focuses his eyes on his favorite toys.
After six months, the delay in mental and physical development becomes even more noticeable. Muscular hypotension increases, previously acquired skills are lost: holding the head and body in an upright position, turning over while lying on horizontal surface, sitting (sitting attempts), grabbing the toy and shifting it from hand to hand. By 8-10 months, start reflexes increase - reactions to sudden sound, light, tactile and olfactory stimuli. Interest in what is happening around the events almost completely disappears. By 12 months, the ability to swallow is impaired, hearing and vision are noticeably reduced, and the breathing cycle becomes difficult. Muscles undergo atrophy, paralysis develops, convulsions in the form of tonic-clonic generalized and partial seizures. In the second year of life, there are phenomena of decerebrate rigidity, bulbar-pseudobulbar syndrome.
The juvenile form debuts with less obvious symptoms. At the initial stage, emotional instability increases somewhat, when performing complex motor complexes - running, walking, writing quickly - a barely noticeable discoordination of movements appears. After some time, clumsiness and awkwardness increase, are noticed by others and by the child himself. By adolescence, the gait becomes shaky, unstable. Hyperkinesias are formed - sudden involuntary movements of various muscle groups. Disorders of coordination do not allow to continue schooling. In parallel, speech disorders of a complex cerebellar-dysarthric nature appear: smoothness and rhythm are lost, pronunciation becomes slow, blurred, indistinct. Late stages of the disease are characterized by frequent epileptic seizures, a persistent decrease in intellectual functions (dementia), loss of voluntary movements, and paralysis.
The chronic form of the disease has less pronounced symptoms, the course is relatively mild. Patients experience mood swings, clumsiness, pronunciation worsens. For several years, intellectual functions have been declining: the ability to think abstractly, compare and analyze phenomena and objects is lost, forgetfulness and absent-mindedness are increasing. A few years after the onset of the disease, mental disorders develop: patients are inadequate in behavior, affectively excitable, prone to states of agitation and deep depression, prone to psychosis with hallucinations and delusions. With a long course, organic dementia is formed.
Complications
The 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, convulse, which is accompanied by a high risk of suffocation (retraction of the root of the tongue), and fatal injuries. Infections are the main complication of the acute infantile form of the disease: children have reduced functions immune system, damage to the respiratory system is recurrent, proceeds extremely hard. A common cause of death is pneumonia.
Diagnostics
The examination is carried out by a pediatric neurologist, ophthalmologist, geneticist, psychiatrist. The process of making a diagnosis begins with the collection of clinical and anamnestic data. As a rule, cases of BTS are detected in relatives, the presence of a period of normal development of the patient, then degradation - the decay of acquired skills, formed functions. Differential Diagnosis aims to exclude degenerative diseases of the central nervous system, juvenile idiocy, epilepsy. To confirm the diagnosis, the following procedures are performed:
- Fundus examination. Ophthalmoscopy reveals a red spot on the retina opposite the pupil. It is an accumulation of gangliosides in ganglion cells.
- Blood chemistry. A laboratory test determines the content of alpha subunits of hexosaminidase A. In the acute childhood form of pathology, the final values are close to or equal to zero. In the subacute and chronic course of the disease, residual activity of the enzyme is detected.
- Microscopic examination of neurons. The content of gangliosides is studied in biomaterial samples. The detection of cell degeneration is characteristic: an increase in size, swelling, “balloon-like” swelling, filling with a fine-grained lipoid substance.
Treatment of Tay-Sachs disease
Currently effective ways therapies are not available. Health care patients is aimed at eliminating symptoms and maintaining life. Palliative care includes switching to tube feeding, as patients lose their swallowing reflex, the use of antibiotics, antiviral and immunostimulatory drugs to combat concomitant infectious diseases. Therapy with antiepileptic drugs does not bring a positive result.
The search for possible treatments for BPS continues. Research is being conducted in three directions: the possibilities of enzyme replacement, gene and substrate-reducing therapy are being studied. Replacement of the missing enzyme is ineffective due to the large size of hexosaminidase molecules, which are unable to pass through the blood-brain barrier and neuronal membrane. Among the methods of gene therapy, the introduction of new genetic material into cells using a viral vector and stem cell transplantation have been tested. But no positive results have been obtained, research continues. The most promising is substrate-reducing therapy using the enzyme sialidase, which stimulates the catabolism of GM2 gangliosides. Development expected pharmacological preparation, which increases the expression of lysosomal sialidases inside neurons.
Forecast and prevention
The outcome of the disease is relatively favorable in the late form, characterized by the slow development of symptoms. When the disease occurs in childhood and adolescence, death is inevitable. To reduce the incidence rate, a screening test is used that determines the level of the enzyme, its biochemical activity. The result allows you to identify carriers of the mutation, send them to a medical genetic examination when planning a pregnancy. If the carriage of the defective gene is determined in both spouses or there were cases of the disease among relatives, prenatal genetic diagnosis is performed in the first trimester of pregnancy.
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 got its name from two scientists who contributed to the study of this disease - the Englishman Warren Tey 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 per 250 thousand people.
What provokes this disease?
Tay Sachs disease develops only if the parents together are carriers of the mutant gene, and the child inherits two genes with a defect. If the carrier of the gene is one of the parents, then the probability of getting sick in a child is almost zero. But, most likely, he will also be a carrier of this disease.
What happens in this disease in the body? 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, as well as responsible for the breakdown of complex natural lipids - gangliosides in cells. In a healthy organism, there is an invariable process of synthesis and breakdown of gangliosides, and this process is very precise and any failure of it leads to irreversible consequences. As a result of a genetic failure, gangliosides do not break 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 a person develops certain symptoms of the disease.
What is the clinical picture of this disease?
At birth, a baby diagnosed with Tay Sachs syndrome looks completely healthy. The first signs of the disease appear at six months. Until this age, a completely healthy-looking baby develops as expected: holds its head, cooing, crawling. But, progressing and accumulating gangliosides in the body, the child gradually begins to lose the acquired skills. The kid stops responding to the environment, his gaze rushes to one point, apathy develops. After a while, mental development stops and blindness develops. Over time, the child's face becomes like a doll. The result of the disease is disability and early death.
Consider the symptoms as the child grows:
- By 6 months, the child begins to lose contact with the outside world, ceases to recognize relatives, reacts only to very loud sounds, cannot focus on a hanging toy, his eyes twitch and vision deteriorates.
- By 10 months, the baby becomes less active, motor functions are disturbed: it is difficult for the baby to sit, roll over and crawl. Hearing and vision are dulled, the baby becomes apathetic.
- After 1 year of life, the disease progresses very quickly. His mental retardation is noticeable in the child, he quickly loses his sight, hearing, muscle activity worsens, breathing difficulties appear, seizures begin.
It is important! Children who develop symptoms of Tay Sachs disease in infancy live to the age of five.
Late onset of symptoms
Sometimes the symptoms of the disease do not appear immediately. There are two more forms of this disease.
Juvenile hexasaminidase type A deficiency
This form of severe illness appears in children from 2 to 5 years. The development of the disease is slow, in contrast to the clinical form. In this case, the symptoms may not be noticed immediately. Mood swings and some clumsiness in movement do not attract much attention. In addition, at this age, whims are normal.
But later symptoms attract attention:
- the child develops muscle weakness;
- convulsive twitches;
- impaired thinking abilities and slurred speech.
Unfortunately, all these signs lead to disability. Death occurs around 15-16 years of age.
Chronic form of hexasaminidase deficiency
It usually occurs in people in their 30s. The course of the disease is weak. It develops gradually, proceeds relatively easily: mood swings, clumsiness can be noticeable, slurred speech appears, mental abnormalities, intelligence decreases, muscle weakness, seizures occur. Due to the fact that this particular form of the disease was discovered recently, it is impossible to make a forecast for the future. Only one thing is clear that this form of the disease will inevitably lead to disability. Life expectancy depends on many factors.
How is the disease diagnosed?
Today, medicine has gone far ahead, and Tay Sachs disease can be diagnosed both in an infant and even before birth.
If there is a suspicion that the baby has Tay Sachs syndrome, first of all, you need to contact an ophthalmologist.
The first sign of the disease can be diagnosed by the fundus. If the child is sick, then you can see a cherry-red spot. This characteristic of the disease is the accumulation of gangliosides in the cells of the retina.
Further testing includes:
- extensive blood test - screening - test;
- as well as microscopic analysis of neurons.
Screening test - shows whether a protein is produced in the child's body - hexasaminidase A or not. This test is carried out with any form of the disease.
Microscopic analysis of neurons is the detection of gangliosides in neurons. With a large number of 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 a 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 analysis is taken using a blood sample from the placenta. 
Cause of Tay-Sachs disease
Tay-Sachs disease affects only a child who has inherited two defective genes at once: from his father and mother. If only one of the parents has the damaged gene, then the child most likely will not get sick, but will turn out to be a carrier, which is risky for his offspring.
This gene is responsible for the production of a special enzyme - hexosaminidase. It contributes to the breakdown of fatty substances (gangliosides), which ensure the normal activity of nerve cells.
This is what happens in a healthy body: gangliosides, being synthesized, are split. If not, they accumulate and deposit in the brain, blocking the work of nerve cells. And this leads to severe symptoms.
Tay-Sachs disease: symptoms
It is difficult to suspect the disease from the very beginning in a child. Usually, symptoms begin to appear from 4-6 months:
- the child reacts poorly to light and does not focus well on the subject;
- painfully reacts to noise, even an ordinary human voice frightens him;
- examination reveals changes in the retina.
The second moment of manifestation of the symptoms of the disease is a decrease in the motor activity of the child from the age of 6 months. He cannot sit, rolls over badly, and walking also has problems. As a result, muscle atrophy or paralysis develops, which leads to the fact that the child can no longer swallow and even breathe on his own.
All this, together with poor vision, hearing and their loss subsequently leads to disability. The head becomes disproportionately large. Seizures are common between the first and second years of life.
If the disease manifests itself at an early age, the child usually dies before reaching 4-5 years of age.
In another case, the disease can progress in the period from 14 to 30 years. In adults, the symptoms are milder:
- speech may be impaired;
- gait, coordination and fine motor skills suffer;
- observed muscle spasms;
- vision, hearing and intelligence deteriorate.
A presumptive diagnosis is made after examination by an ophthalmologist. When examining the organs of vision, a specialist can usually detect a cherry red spot in the fundus, which is typical for this disease.
Further, the analysis to determine the amount of the enzyme in the fluids and tissues of the subject helps to confirm the assumptions. A blood test and a skin biopsy are needed. If the analysis is positive, this confirms the diagnosis or carriage.
To determine whether there is a disease, before the birth of a child, allows amniocentesis - an analysis of the amniotic fluid obtained by puncturing the fetal bladder.
Treatment and prognosis
Tay-Sachs disease has no cure. The clinical picture usually increases gradually and also gradually leads to the extinction of the child.
The prognosis of the disease is disappointing: first, the disease leads to disability, and subsequently to death. The life expectancy of the patient depends primarily on the severity of the symptoms of the disease. It happens that such patients can live as long as healthy people.
Tay-Sachs disease - causes
Tay-Sachs disease is a rather rare disease, and certain ethnic groups are predominantly susceptible to it. Most often, this disease affects the French population of Canadian Quebec and Louisiana, as well as the Jews of Eastern Europe. In Ashkenazi Jews, this pathology is observed in 1 in 4,000 newborns.
Tay-Sachs disease is inherited in an autosomal recessive manner. This suggests that only a child who has inherited two defective genes at once can get sick - the first from the mother and the other from the father. If only one of the biological parents has a defective gene, the child will not get sick, but with a 50% chance will become a carrier of the defective gene, thereby putting his future offspring at risk.
What can happen if both parents have the defective gene:
With a probability of 25%, the child will not be a carrier of this gene and will be born completely healthy
With a probability of 50%, the child will be a carrier of this gene and be born completely healthy
There is a 25% chance that a child will inherit two affected genes and be born with Tay-Sachs disease
The mechanism of development of this pathology is the accumulation in the nervous system of gangliosides - substances responsible for the normal functioning of nerve cells. Gangliosides in a healthy body are constantly synthesized and therefore constantly broken down, and enzyme systems are responsible for maintaining a delicate balance between synthesis and decay. Sick babies have a damaged gene responsible for the synthesis of the type A hexosaminidase enzyme. The body of children with a congenital deficiency of this enzyme is not able to constantly break down rapidly formed and accumulating fatty substances - gangliosides, which, being deposited in the brain, block the functioning of nerve cells, which leads to very severe symptoms
Tay-Sachs disease - symptoms
Tay-Sachs disease usually affects babies around six months of age. At the beginning of the development of the disease, the child loses contact with the outside world, he has a fixed gaze directed at one point, he becomes apathetic and reacts exclusively to a loud sound. After that, the child loses the acquired skills (for example, stops crawling), retards mental development, and after a while goes blind. Muscle functions(the ability to eat, drink, move, make sounds, etc.) are significantly reduced, sometimes up to their complete loss, the head becomes disproportionately large. In the later stages of the course of the disease (usually between 1 and 2 years of age), seizures may occur. In most cases, the child dies before the age of five.
Separation of symptoms by age:
From 3 to 6 months: the child has difficulty focusing on an object, visual perception worsens, eyes twitch, unreasonable reproduction of rather loud sounds is observed
From 6 to 10 months: the baby has hypotonia (decrease in muscle tone), he becomes less active, hearing and vision deteriorate significantly, his head noticeably increases in size (macrocephaly), motor skills become dull, it is difficult for the child to roll over and sit
After 10 months: mental retardation becomes apparent, blindness develops, paralysis develops, breathing difficulties are present, swallowing disorders, seizures
Clinical variants of Tay-Sachs disease:
Chronic deficiency of hexosaminidase (type A). Symptoms of this disease can develop both at the age of 3-5 years, and at the age of thirty. The disease proceeds relatively easily: in patients, speech may be slightly disturbed (it becomes slurred), fine motor skills, coordination and gait suffer; muscle spasms, mental disturbances and decreased intelligence may be observed. In most patients, hearing and vision deteriorate markedly. Due to the fact that this form of Tay-Sachs disease was discovered quite recently, the long-term prognosis of the future life of such patients is debatable. With a high degree of probability, it can be argued that the disease gradually leads to disability and subsequent death.
Juvenile hexosaminidase deficiency (type A). Symptoms of this disease develop in the age range from 2 to 5 years. Despite the fact that this form of the disease progresses much more slowly than it classic version, the death of a child still inevitably occurs at the age of about 15 years
Diagnosis of Tay-Sachs disease
The assumption that a child has this disease arises when, as a result of an examination of the baby by an ophthalmologist, a cherry-red spot is found on the fundus. This area on the retina indicates that it is in this place in the ganglion cells of the retina that an increased accumulation of gangliosides is observed. After this observation, the doctor prescribes the following types of studies: microscopic analysis of neurons, screening, detailed blood tests
Tay-Sachs disease - treatment
Unfortunately, there is no cure for Tay-Sachs disease. Even in case best care, almost all children with childhood forms of this disease live to a maximum of five years. Throughout life, patients receive palliative care (tube feeding with the inclusion of supplements) to alleviate the present symptoms. nutrients, careful skin care, etc.). Anticonvulsants are most often powerless against seizures.
Prevention of this disease consists in the mandatory examination of married couples for the presence of the Tay-Sachs disease gene. If both spouses have such a gene, they are advised not to have children. If a woman is already pregnant at the time the gene is diagnosed, an amniocentesis may be performed to identify defective genes in the fetus.
Image from lori.ru
Tay-Sachs disease, or infantile gangliosidosis, along with Gaucher 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
It is detected in young children, 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 his 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 occurs 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, the results of biochemical studies - determine the activity of the enzyme in blood leukocytes and tissues. 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. The greatest importance is attached 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 refers to hereditary diseases of the 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 Sacks (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 of a 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.
The driving force for the development of 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 are deposited 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 head size 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 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.
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. Medical care consists in simply alleviating the symptoms of the manifestation of the disease, but if we are talking about a late form, then 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 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 a hereditary disease that occurs extremely rarely, has an autosomal recessive inheritance and is characterized by damage to the central nervous system.
This disease, which belongs to the group of lysosomal storage diseases, is also known as early infantile 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 (an intermediary 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 with palliative care, which includes tube feeding, 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 that 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 pregnancy. 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 are not broken down, a sufficient amount of them accumulates 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. Tay-Sachs syndrome in chronic form was opened relatively recently, so it is not possible to make forecasts 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
In 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 who are 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.
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);
- 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 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 GM2 type 1 gangliosidosis. There are two other related diseases called Sandhoff's disease and hexosaminidase activator deficiency, which 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 is ongoing to develop 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 being used to treat people with other lysosomal storage disorders, including Hurler's syndrome, Fabry syndrome, and Gaucher's 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 lead to 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 marked improvement in neurological or psychiatric 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
In the clinical practice of 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 of neurological disorders occur 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 the causes and pathogenesis of 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 also manifests itself convulsive syndrome.
These are 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 of the nervous system (stroke), drugs called anticoagulants are used. They prevent the formation of blood clots in 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 different molecular defects in the gene responsible for the metabolism of this drug in the human body lead to such a different result. Thus, molecular diagnostics of an individual tendency to thrombosis and testing of the genes responsible for the exchange of anticoagulants make it possible to choose an INDIVIDUAL effective therapeutic dose of the drug.
Consultation of a geneticist in Samara
Neurogenetics allows you to most accurately determine the prognosis for the patient's life and health, 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 of a hereditary disease in an unborn child in the prenatal period.
We have a geneticist in our clinic.