Tay-Sachs disease: symptoms, causes, treatment and prevention

Tay-Sachs disease is a rare pathology of genetic origin that usually appears in childhood.

Tay-Sachs disease is a rare medical condition that, although rare in the majority of the population which, although rare in the majority of the population, appears to be highly prevalent in some ethnic groups.

It is a genetic disease that affects the nervous system, causing lipids present in nerve cells to accumulate and eventually damage them.

Let's discover what causes this disease, what are its main symptoms, how it is treated and how it can be diagnosed, as well as to see in which populations it is more likely to find people with Tay-Sachs disease.

What is Tay-Sachs disease?

Tay-Sachs disease, also called GM2 gangliosidosis and lysosomal storage disease, is a life-threatening genetic, neurodegenerative, medical condition that often affects children at an early age. a life-threatening medical, neurodegenerative and genetic condition that usually affects children at a young age.. It is transmitted from parents to children, i.e., it is inherited, specifically in an autosomal recessive manner. In fact, it has been found that certain populations, such as Ashkenazi Jews and the Amish community are prone to have cases of this disease.

It is a rare disease, which when the body is unable to break down fatty substances, causing them to accumulate to toxic levels in the nervous system of the affected person, causing in the nervous system of the affected person, causing this system to progressively degenerate. The child loses muscle control, suffers visual loss and paralysis until he/she finally dies.

Causes

Tay-Sachs disease is caused by a defective gene on chromosome 15 and is inherited in an autosomal recessive manner. If both parents have a defective copy of the gene, there is a 25% chance that their child will have the disease.

To manifest the disease, he or she must have inherited both copies of the defective gene, one from the father and one from the mother.One from the father and the other from the mother. If you have inherited only one defective chromosome, you will not manifest the disease, but you will be a carrier.

This gene in non-pathological conditions codes for the alpha subunit of the enzyme hexosaminidase A or Hex-A, a protein that helps to break down gangliosides, especially GM2. These gangliosides are a group of lipids found in nerve tissue.

Hex-A is normally found in the lysosomes of nerve cells, organelles that degrade molecules that are used to break down gangliosides.organelles that degrade large molecules in order to recycle them. Without the enzyme, the gangliosides accumulate in the neurons and gradually damage them.

It should be noted that although people who have two copies of the defective gene are the ones who will manifest Tay-Sachs disease, without being able to synthesize hexosaminidase A, people who are carriers may have altered levels of this enzyme. They do produce it and, therefore, do not suffer the symptoms, but they only synthesize half the normal amount of Hex-A.

Risk factors.

Anyone can carry the defective gene that causes Tay-Sachs disease. However, it has been shown that certain populations have more cases of this disease because the defective gene is more prevalent in their ethnic groups..

A case in point is the Ashkenazi Jewish population, in which one in 27 members is a carrier of the gene causing this disease. Among the populations where the defective gene is most prevalent are:

• Eastern and Central European Jewish communities, especially Ashkenazi.
• French Canadian communities of Quebec.
• Old Order Amish people of Pennsylvania.
• Louisiana Cajun community.

Symptoms

There are three types of Tay-Sachs disease: infantile, juvenile, and adult.. These forms vary in their onset and symptomatology, however, juvenile and adult forms are extremely rare.

The most common form is the infantile form, which causes very early mortality. The disease already causes damage when the fetus is still in the womb, and symptoms are usually visible when the baby is between 3 and 6 months old. In most cases, the child dies at about 4 to 5 years of age.

Among the symptoms that can be found in this disease we have:

• Deafness
• Blindness
• Loss of muscle tone
• Loss of motor skills: the baby does not roll over, crawl or sit up.
• Paralysis
• Slowed growth
• Delayed intellectual and social development
• Dementia (loss of brain function)
• Increased startle reflex -- startles when hearing loud noises
• Irritability
• Listlessness
• Seizures
• Cherry-red spots in the eyes

Cases of this disease have been documented in adults, but it is very rare and has a very late onset. and has a very late onset. It is not detectable until the age of 20 or 30 years and, in general, its symptoms are less severe than in the infantile form, although it may involve a great degree of disability in the patient.

Diagnosis

To confirm that it is a case of Tay-Sachs the first thing to do is to find out if there is a history of the disease in both parents.The results of this study are used to determine whether they belong to one of the four ethnic groups with the highest frequency of the defective gene.

In addition to this, tests are done on the level of enzymes in the baby's Blood and body tissue. tests of enzyme levels in the baby's blood and body tissue to check the levels of hexosaminidase.to check the levels of hexosaminidase. An eye exam will also be done to see if the cherry-red spots in the macula are present.

Treatment

There is currently no effective treatment that cures Tay-Sachs disease. Unfortunately, if an infant is diagnosed with Tay-Sachs disease, he or she is not expected to live more than 5 years. However, research has been done on the use of the use of ganglioside synthesis inhibitors and Hex-A enzyme replacement therapies have been investigated as potential treatments for this rare disease. as potential treatments for this rare disease.

Gene therapies have also been investigated. One of them would consist of including, by means of genetic engineering, a gene in the DNA of the child with the defective gene that solves the anomalous synthesis of the Hex-A enzyme. This technology is still very experimental and highly controversial, as well as being quite expensive.

Prevention

The surest way to ensure that you will not get Tay-Sachs disease is for two people who carry the defective gene not to have children in common. Genetic testing can detect whether or not you are a carrier.In addition to being aware if there have been cases in the family of children who have died at an early age.

If both partners have the defective gene, they should be aware that they have a 25% chance of having a child with the disease.

If the mother is already pregnant, the amniotic fluid can be tested to determine whether or not the baby will have the disease. In case you have inherited two defective copies of the gene, it is confirmed that you could manifest the disease, and it is the decision of the parents to terminate the pregnancy.

In fertilization therapies, there is the possibility of performing a preimplantation genetic diagnosis to make sure that the baby will not have the disease. It consists of fertilizing the eggs taken from the mother and, once the embryos are very early, selecting those that do not have any copy of the defective gene.

This same method has been used for other diseases of genetic origin, such as cystic fibrosis, sickle cell anemia and Huntington's disease, but it must be said that it is a very expensive method that requires very invasive medical technology.

Bibliographic references

• Kwon JM. (2016) Neurodegenerative disorders of childhood. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier; capítulo 599.
• Nussbaum RL, McInnes RR, Willard HF (2016). The molecular, biochemical, and cellular basis of genetic disease. In: Nussbaum RL, McInnes RR, Willard HF, eds. Thompson and Thompson Genetics in Medicine. 8th ed. Philadelphia, PA: Elsevier: capítulo 12.
• Wapner RJ, Dugoff L (2019). Prenatal diagnosis of congenital disorders. In: Resnik R, Lockwood CJ, Moore TR, Greene MF, Copel JA, Silver RM, eds. Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. 8th ed. Philadelphia, PA: Elsevier; capítulo 32.