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

Tay-Sachs disease is a rare medical condition that, although rare in the majority of the population, it seems that there are ethnic groups in which it has a high prevalence.

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

Let's find out what causes this disease, what are its main symptoms, how it is treated and how it is can diagnose, in addition to seeing in which populations it is most likely to find people with the disease Tay-Sachs.

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What is Tay-Sachs disease?

Tay-Sachs disease, also called GM2 gangliosidosis and lysosomal storage disease, is a life-threatening medical, neurodegenerative, and genetic condition that often affects children at an early age. Its form of transmission is from parents to children, that is, it is hereditary, specifically autosomal recessive. In fact, it has been seen that certain populations, such as Ashkenazi Jews and the Amish community, are prone to having cases of this disease.

It is a rare disease, which occurs when the body cannot break down fatty substances, causing them to accumulate at toxic levels in the affected person's nervous system, causing this system to progressively degenerate. The boy gradually loses muscle control, suffers visual loss and paralysis until he 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 will be a 25% chance that their child will have the disease.

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

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

Hex-A is normally found in the lysosomes of nerve cells., organelles that break down large molecules for recycling. Without the enzyme, gangliosides accumulate in neurons and gradually damage them.

It should be said that although people who have both copies of the defective gene are the ones who will manifest the disease of Tay-Sachs, without being able to synthesize hexosaminidase A, people who are carriers may present 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.

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Risk factor's

Anyone can carry the defective gene that causes Tay-Sachs disease. However, it has been seen that there are certain populations that 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 carries the gene that causes this disease. Among the populations where the defective gene is more prevalent we have:

• Jewish communities of Eastern and Central Europe, mainly Ashkenazi.
• French Canadian Communities of Quebec.
• Amish people of the Old Order of Pennsylvania.
• Cajun community of Louisiana.

Symptoms

There are three types of Tay-Sachs disease: childhood, juvenile and adult. These forms vary in their appearance and symptoms, however, it must be said that the juvenile and adult forms are extremely rare.

The most common is the infantile form, which involves 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 with about 4 or 5 years.

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
• slow growth
• Delayed intellectual and social development
• Dementia (loss of brain function)
• Increased startle reflex: startles when hearing loud noises.
• Irritability
• Reluctance
• seizures
• Cherry red spots on the eyes

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

Diagnosis

To confirm that it is a Tay-Sachs case, the first thing to do is find out if there is a history of the disease in both parents, in addition to finding out if they are part of one of the four ethnic groups with the highest frequency of the defective gene.

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

Treatment

There is currently no effective treatment to cure Tay-Sachs disease. Unfortunately, if this disease is diagnosed in a baby, it is expected that she will not live more than 5 years. Nevertheless, the use of ganglioside synthesis inhibitors and Hex-A enzyme replacement therapies has been investigated as potential treatments for this rare disease.

It has also been investigated in gene therapies. One of them would consist of, by means of genetic engineering, including in the DNA of the child with the defective gene a gene that solves the abnormal synthesis of the Hex-A enzyme. It is a technology that 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 faulty gene not to have children together. Genetic tests can detect whether or not you are a carrier, in addition to being aware if there have been cases of children with deaths at an early age in the family.

In the event that both members of the couple have the defective gene, they should be aware that they have a 25% chance of having a child with the disease.

In case the mother is already pregnant, the amniotic fluid can be analyzed to determine if the baby will present the disease or not. In the event that she has inherited two defective copies of the gene, it is confirmed that she could indeed manifest the disease, and it is the parents' decision to terminate the pregnancy.

In fertilization therapies there is the possibility of making a preimplantation genetic diagnosis to make sure that the baby will not have the disease. It consists of fertilizing the eggs extracted from the mother and, once very primitive embryos are obtained, 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, cell anemia sickle cell disease and Huntington's disease, but it can be said that it is a very expensive method that requires very invasive.

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; chapter 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: Chapter 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; chapter 32.