Resource: One Wrong Letter

Tay-Sachs disease is a fatal genetic disorder that causes progressive destruction of the brain in young children. The majority of children with Tay-Sachs appear to develop normally for the first six months of life before rapidly regressing. They develop severe seizures usually by the age of two. By three, most have become completely incapacitated. Children with Tay-Sachs usually die before they reach age five.

The disease is caused by the absence of a vital enzyme called hexosaminidase A, or Hex-A. This enzyme allows the body to break down a fat called GM2 ganglioside. Children with Tay-Sachs do not produce Hex-A, and thus have no way to metabolize GM2 ganglioside. The fat builds up in the body, especially in the brain and other nervous tissue. This buildup of fat creates swelling and ultimately an increase in cranial pressure that causes nerve cells to die.

Each of us has two genes responsible for coding for the enzyme Hex-A. We receive one of these genes from our mother and one from our father. Most of us have two normal, or active, Hex-A genes. Some people have one active and one inactive gene. Fortunately, that's all that is required to be free of Tay-Sachs. Tay-Sachs is a recessive disorder, which means that the presence of one "good," or active, Hex-A gene outweighs the presence of an inactive Hex-A gene.

Inactivity in a Hex-A gene is usually caused by a mutation on the gene itself, a mutation that can be passed from one generation to the next. Of the more than fifty mutations that have been identified, one of the most prevalent results from a single base difference. This means just one nucleotide on that gene is different from the normal sequence of an active Hex-A gene. This tiny difference, if a child were to inherit two of the same type, is enough to cause Tay-Sachs.

Unfortunately, even though the Hex-A gene has been identified, there is still no cure for Tay-Sachs, no way to replace bad genes with good ones. All that the identification of the gene can provide so far is a means to test people who think they might be carriers. Since the first Tay-Sachs screen was developed, millions of such people -- especially those in high-risk ethnic groups, like Eastern European Jews, and those who have a family history of Tay-Sachs -- have been tested for the Hex-A mutation.

How can a mutation in a single DNA base affect the production of normal proteins?

How are mutations passed on to offspring?

What does it mean to be a carrier of a disease?

What is the pattern of inheritance for diseases carried by recessive genes?

What is Tay Sachs?