What is the History of the Discovery and Treatment of Tay-Sachs Disease?

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Tay-Sachs disease is a progressive neurological disorder that can appear in several different forms.

The root cause of the disease is a mutation in a gene that produces an enzyme called hexosaminidase A, or Hex-A. Without a functional form of Hex-A, a lipid called GM2 ganglioside accumulates in brain nerve cells and cells in other parts of the body. Accumulation of GM2 ganglioside causes progressive cellular destruction that leads to loss of sight and hearing, and eventual muscle atrophy leading to death.

Children born with Tay-Sachs disease rarely live past the age of four. In rare cases the disease begins to develop in young children of between two and ten years of age; these children tend to die by the age of 15. When the disease is of adult onset it is typically diagnosed in the 20s or 30s and can cause psychiatric illness in addition to physical symptoms. However, adult-onset forms of Tay-Sachs are not always fatal, and do not progress as rapidly and severely as juvenile forms.

Discovery of Tay-Sachs Disease

Tay-Sachs disease is named after the people who made the first discoveries about its diagnostic characteristics and prevalence in certain cultural groups.

In 1881, British ophthalmologist Warren Tay was the first person to note a patient with the retinal red spot that is now known to be typical of the disease.

Six years later in 1887, Bernard Sachs, an American neurologist working at Mount Sinai Hospital in New York, noted some of the characteristic cellular changes that occur in people with the disease. Bernard Sachs was also the first person to note that Jewish people of Eastern European, or Ashkenazi descent, had a greatly increased risk of developing the disease, after seeing several patients from the same family with the disease.

History of Tay-Sachs Disease Genetic Research

Up until the latter half of the twentieth century, Tay-Sachs disease was thought to be a disease of infants only, and later-onset forms of the disease were not recognized as being Tay-Sachs. In the 1970s and 1980s, as new information about the molecular biology of the disease was uncovered, it was determined that adult-onset forms of the disease did exist.

Tay-Sachs is now known to be an autosomal recessive genetic disorder, which means that a child born with the disease has inherited a defective copy of the HEXA gene from each parent.

Much genetic information about the disease has been uncovered in the twenty-first century. By the year 2000, more than one hundred different types of mutation in the HEXA gene had been discovered as a result of genetic testing of people known to be carriers of a mutated gene. All of the HEXA mutations so far discovered have resulted in Hex-A enzymes that are either non-functional, or function abnormally.

Bernard Sachs originally noted the prevalence of Tay-Sachs in Ashkenazi Jews more than one hundred years ago, but more recently it has been discovered that certain other cultural or geographic populations also have a higher incidence of HEXA gene mutations.

These include the Cajun population of southern Louisiana, where it has been noted that among this group of people exists the very same HEXA gene mutation that is so prevalent in Ashkenazi Jews. Genealogical research indicates that this mutation can be traced to a single French couple who lived in the eighteenth century.

Tay-Sachs Disease and Compound Heterozygosity

The development of genetic testing added an enormous amount to the store of knowledge about Tay-Sachs disease, and this disease was one of the first for which genetic screening became available. In addition, Tay-Sachs is one of the first diseases known to exhibit a quality called compound heterozygosity.

In Tay-Sachs, compound heterozygosity occurs when a child inherits a defective HEXA gene from each parent, but in each case the genetic mutation is different. This leads to a state in which the child can make two different “quality levels” of the Hex-A enzyme. If one of those forms of the mutated gene has the ability to make Hex-A protein that retains a low level of functionality, the result is late-onset Tay-Sachs disease.


National Institute of Health MedlinePlus: Tay-Sachs Disease

National Institute of Neurological Disorders and Stroke: Tay-Sachs Disease Information Page

National Tay-Sachs & Allied Diseases Association

U.S. National Library of Medicine Genetics Home Reference: Tay-Sachs Disease