Definition

Hereditary disorder resulting from a deficiency of the enzyme hexosaminidase. Symptoms include blindness, delayed development, seizures and paralysis. Tay-Sachs disease often results in an early death.

What is Tay-Sachs Disease

Tay-Sachs disease is a progressive neurological genetic disorder that appears in three forms: Classic Infantile, Juvenile and Late Onset or Chronic Tay-Sachs.

History

The disease is named for Warren Tay (1843-1927), a British ophthalmologist who in 1881 described a patient with a cherry-red spot on the retina of the eye. It is also named for Bernard Sachs (1858-1944), a New York neurologist whose work several years later provided the first description of the cellular changes in Tay-Sachs disease. Sachs also recognized the familial nature of the disorder, and, by observing numerous cases, he noted that most babies with Tay-Sachs disease at that time were of Eastern European Jewish origin. Today, Tay-Sachs occurs among people of all backgrounds.

Cause

Tay-Sachs disease is caused by the absence or insufficient level 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, also called "substrate," causes progressive damage to the cells. In Classic Infantile the destructive process begins in the fetus early in pregnancy, although the disease is not clinically apparent (symptoms do not start) 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 classic Tay-Sachs disease die early in childhood, usually by the age of 5, although some do live longer.

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Types of Tay-Sachs

There are generally three types of Tay-Sachs disease: Classic (or "Infantile"), Juvenile Onset, and Late Onset (known as LOTS), depending on the nature of the symptoms and when they begin.

While babies with classic Tay-Sachs do not produce any Hex-A, individuals with the Juvenile and LOTS forms produce very small amounts of the enzyme. This is probably why their symptoms begin later in life and generally are milder than in the classic form.

Children with juvenile Tay-Sachs disease develop symptoms between 2 and 10 years of age that resemble those of the Classic form. Although the course of the disease is slower, death generally occurs by age 15.

Individuals with Late-Onset Tay-Sachs disease (also called "Chronic Tay-Sachs" disease) have far milder symptoms than children with the classic or juvenile forms. Symptoms usually begin between adolescence and the mid-30s, although they can begin in childhood. Affected individuals usually do not lose vision or hearing. Some individuals may have loss of certain mental abilities, including problems with memory and comprehension. Symptoms vary greatly in severity and can include slurred speech, muscle weakness, muscle cramps, tremors, unsteady gait and sometimes mental illness. Life expectancy is variable, and in some cases appears to be unaffected.

Rare Late-Onset forms of Sandhoff Disease appear to share many of these symptoms.

Treatment

To date, there is no cure or effective treatment for Tay-Sachs disease. However, there is active research being done in many investigative laboratories in the U.S. and around the world exploring a range of therapeutic approaches.

There is currently a clinical trial testing the potential of a pharmacological chaperone (a drug known as PYR) in the late on-set form of Tay-Sachs. The drug is already approved for human use as it was used to treat malaria. The trials will be conducted in Toronto and New York starting in mid 2009.

Because the disease affects brain cells that are protected by the blood-brain barrier, enzymes such as Hex-A are blocked from entering the brain by the blood. Stem cell transplantation using umbilical cord blood is an investigational procedure attempted with a small number of very young children, but to date there is not enough information for specific results about reversing or slowing damage to the central nervous system in this group with Tay-Sachs disease. A Gene therapy project is entering its second year of research with very promising results in year one and neural stem cell therapy is gaining momentum with the recent change in US Presidents.

Testing

Tay-Sachs carrier testing is vital for individuals in high-risk populations: Ashkenazi Jews, French Canadians, Louisiana Cajun, Pennsylvania Dutch and preliminary data suggests persons of British Isle and Italian decent have an increased carrier rate over the general population.

Carrier testing is best completed before conception. Even if your childbearing years are over, your carrier status can be an extremely important piece of information. If you are a carrier, your close relatives (children, brothers, sisters, cousins, aunts, uncles) should be alerted so they can be tested as well. Tay-Sachs carrier testing is also vital for the close relatives of families with an affected child, regardless of ethnic background, since all parents of children with Tay-Sachs are, by definition, carriers.

To see a list of certified testing labs go to NTSAD and click on Testing then Testing Centers Near You.

Support

Although a cure for Tay-Sachs disease does not exist at the present time, significant progress is being made in the areas of gene therapy, chaperone therapy and cord blood transplants. Support, programs, and services for affected individuals and their families are available through National Tay-Sachs & Allied Diseases Association, Inc. (NTSAD).