Tay-Sachs Disease

Tay-Sachs disease is a rare inherited disorder that causes progressive destruction of nerve cells in the brain and spinal cord (the central nervous system). It can be detected in developing fetuses, and this has drastically reduced its frequency.

Source:NIH ^[1]

History

This disease was first observed in 1881 by Warren Tay, who described fully the characteristic changes in the eye. Sachs, in 1887, investigated it from the neurological point of view and showed that it is a familial disease.

Other Names

• B variant GM2 gangliosidosis
• GM2 gangliosidosis, type 1
• HexA deficiency
• Hexosaminidase A deficiency
• Hexosaminidase alpha-subunit deficiency (variant B)
• Sphingolipidosis, Tay-Sachs
• TSD

Symptoms

The most common form of Tay-Sachs disease begins in infancy. Infants with this disorder typically appear normal until the age of three to six months, when development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Tay-Sachs disease experience seizures, vision and hearing loss, mental retardation, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Children with this severe infantile form of Tay-Sachs disease usually survive only into early childhood.

Other forms of Tay-Sachs disease are much rarer. Symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Tay-Sachs disease. As in the infantile form, mental abilities and coordination are affected. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Tay-Sachs disease.

Causes

Mutations in the HEXA gene cause Tay-Sachs disease. The HEXA gene provides instructions for making part of an enzyme called beta-hexosaminidase A, which plays a critical role in the central nervous system. This enzyme is located in cellular structures called lysosomes, which are the cell's recycling centers. Within lysosomes, beta-hexosaminidase A helps break down a fatty substance known as GM2 ganglioside. Mutations in the HEXA gene disrupt the activity of beta-hexosaminidase A, preventing the breakdown of this substance. As a result, the enzyme accumulates to toxic levels in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of nerve cells, which causes the signs and symptoms of Tay-Sachs disease.

Diagnosis

Pregnant mothers can have their unborn babies screened for the Hex A deficit that causes Tay-Sachs disease. If the tests do not detect Hex A, the infant has Tay-Sachs disease. If the tests do detect Hex A, the infant doesn’t have the disease.

Between the 10th and 12th weeks of pregnancy, an expectant mother can get a chorionic villus sampling, or CVS, in which a small sample of the placenta is drawn into a needle or a small tube for analysis.

Between the 15th and 18th weeks of pregnancy, the mother can also have an amniocentesis to screen for the Tay-Sachs gene. In this test, a needle is inserted into the mother's belly to draw a sample of the amniotic fluid that surrounds the fetus.

Treatment

There is no cure for any form of Tay-Sachs disease, but the symptoms can b e managed with medications. Most often the medications used control pain, seizures and muscle spasticity.

Prevention

Couples who are considering having children – or are already expecting – can get screened for the Tay-Sachs gene with a simple blood test. If both the mother and father carry the Tay-Sachs gene, an obstetrician/gynecologist may refer the couple to a genetic counselor for more information. ^[2]

Chances of Developing Tay-Sachs disease

Tay-Sachs disease is very rare in the general population. The genetic mutations that cause this disease are more common in people of Ashkenazi (eastern and central European) Jewish heritage than in those with other backgrounds. In recent years, however, screening for mutations and genetic counseling have made the condition much less frequent in this population.

The genetic mutations that cause Tay-Sachs disease are also more common in certain French-Canadian communities of Quebec, the Old Order Amish community in Pennsylvania, and the Cajun population of Louisiana.

Heredity

This condition is inherited in an autosomal recessive pattern, which means that a person needs to have mutations in both copies of the gene in order to have the disease. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs of the condition.

Related Problems

Nerve degeneration in Tay-Sachs disease has several consequences:

• blindness
• deafness
• seizures
• movement disorders
• mental retardation
• emotional disorders

Expected Outcome

Babies who are born with Tay-Sachs this disease usually die in early childhood.

Research

Several approaches to the treatment of Tay-Sachs disease are being investigated. One approach is called substrate deprivation or substrate reduction. Substrate deprivation uses drugs to prevent the synthesis of gangliosides, the substance that accumulates in the nerves of children with Tay-Sachs. Gangliosides are synthesized in a multistep process that contains intermediary compounds. Preventing the synthesis of any one of these compounds could reduce accumulation of gangliosides. Some experiments in animal models of Tay-Sachs disease have already shown that the drug miglustat prevents ganglioside accumulation by preventing its synthesis.^[3]

References

1. ↑ http://www.ncbi.nlm.nih.gov/disease/Tay_Sachs.html
2. ↑ Kidshealth.org Tay Sachs Information Page
3. ↑ Jakóbkiewicz-Banecka J, Wegrzyn A, Wegrzyn G. Substrate deprivation therapy: a new hope for patients suffering from neuronopathic forms of inherited lysosomal storage diseases. J Appl Genet. 2007;48(4):383-8. Review. Abstract | PDF

External Links

Links from the U.S. National Library of Medicine:

Educational resources from Genetics Home Reference

Patient support from Genetics Home Reference

Patient support - For patients and families]