THE CLASSICAL FORM OF TAY-SACHS disease (TSD) is a fatal, recessive genetic disorder in children that causes progressive destruction of the central nervous system.
When a person has Tay-Sachs disease, harmful quantities of a fatty substance called ganglioside GM2 accumulate in the nerve cells in the brain. Infants with Tay-Sachs disease appear to develop normally for the first few months of life. Then, as nerve cells become distended with fatty material, a relentless deterioration of mental and physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in
Tay-Sachs disease is caused by the absence of a vital enzyme called hexosaminidase A (Hex-A). Without Hex-A, a fatty substance or lipid called GM2 ganglioside accumulates abnormally in cells, especially in the nerve cells of the brain. This ongoing accumulation causes progressive damage to the cells. The destructive process begins in the fetus early in pregnancy, although the disease is not clinically apparent until the child is several months old. By the time a child with Tay-Sachs disease is three or four years old, the nervous system is so badly affected that life itself cannot be supported. Even with the best of care, all children with classical Tay-Sachs disease die early in childhood, usually by the age of five.
The most common form of Tay-Sachs disease begins in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 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.
These show neurons at stages of intraneuronal storage with resultant destruction of the involved neuron. This can be seen in lipid and mucopolysaccaride storage diseases. In this case the child had Tay Sachs disease
In a healthy neuron, top, lysosomes act as the waste processing center of the cell. In Tay-Sachs disease, genetic deficiencies hobble lysosome enzymes that break down fatty cell products, also known as gangliosides, which build up and destroy the cell.
The groups most at risk are eastern Europeans of (Ashkenazi) Jewish decent, French Canadian living near the
One of the most insidious features of Tay-Sachs disease is it often strikes families with no prior history of the disease. Large and diverse family trees allow the carriers of the Tay-Sachs disease to go without expression for generations until unexpectedly a child is diagnosed and the family submits to carrier testing.
A person can only be affected by Tay-Sachs Disease when two carrier parents pass a Hex-A gene mutation to their child. When two-carrier parents have children, three outcomes are possible.
1. Both parents do not pass the gene mutation to the child – child will be normal.
2. One parent pass the gene mutation to the child but the other does not – child will not suffer from TSD but will be a carrier of the Tay-Sachs gene.
3. Both parents pass the gene mutation to the child. Child will suffer from TSD and depending upon the mutations passed will likely die at a very young age.
As we look at these four possible outcome – there is a 25% chance both parents do not pass the gene mutation to the child; a 50% chance one of the parents passes the gene mutations; and a 25% chance both parents pass the gene mutation. See the chart below:
If only one of the parents is a carrier of the Tay-Sachs gene mutation then only two outcomes are:
1. That one parent passes the gene mutation to the child and the child is a carrier of the Gene.
2 . The parent does not pass the gene mutation and the child is normal and not a carrier.
A baby with TSD has no signs or symptoms of the disease at birth. Symptoms usually appear 3 to 6 months after birth. The symptoms are caused by damage to the brain and nerve cells from the buildup of fatty compounds. An early sign of the infantile form of Tay-Sachs is a red spot on the retina. See an illustration of the retina.
At 3 to 6 months:
As a child with Tay-Sachs grows older, he or she may become blind, mentally retarded, paralyzed, and unresponsive to the environment. The child also may have seizures, difficulty swallowing, and difficulty breathing. Children with Tay-Sachs disease rarely live beyond 4 or 5 years of age.
Symptoms of late-onset Tay-Saych disease(LOTS) usually develop between adolescence and the mid-30s. The symptoms vary among individuals, depending on the amount of hex A being produced by the body. At first, symptoms such as clumsiness or mood changes are subtle and may go unnoticed. Other symptoms that may develop include:
The Cure
Unfortunately, there is no cure for Tay-Sachs disease and there is no way to prevent or slow the progression of the disorder. The disease is fatal, but children can be made to feel more comfortable through the use of certain medications and therapies.
Prevention
Prevention involves identifying carriers of the disease and providing them with appropriate information concerning the chance of their offspring having Tay-Sachs disease. When the levels of hexosaminidase A are half the normal level a person is a carrier of the defective gene. Blood tests of carriers reveals reduction of Hexosaminidase A.
