About Tay-Sachs

Tay-Sachs is a rare hereditary disease caused by a genetic mutation that leaves the body unable to produce an enzyme (known as Hex-A) necessary for fat metabolism in nerve cells. Without this enzyme, central nervous system degeneration ensues. The disease is named for a British ophthalmologist, Warren Tay, who first described the disease, in 1881, and a New York neurologist, Bernard Sachs, who first described the cellular changes and the genetic nature of the disease, in 1887.

In infants, Tay-Sachs is characterized by progressive mental deterioration, blindness, paralysis, epileptic seizures, and death, usually between ages two and five. Late-onset Tay-Sachs occurs in persons who have a genetic mutation that is similar but allows for some production of the missing enzyme. There is currently no treatment for Tay-Sachs Disease.

What are the symptoms of Tay-Sachs Disease?
Most babies with classic Tay-Sachs Disease are born happy and seemingly healthy. There is typically no indication of any signs of illness. The first 6 to 9 months of life have all of the typical ups and downs familiar to most parents: smiling, crying, sleepless nights, late-night feeds, learning to roll over, beginning to babble, starting solid foods, laughing with delight, and cooing peacefully.

Then, typically by 6 to 9 months of age, the baby begins to make less and less eye contact with the parents. There is an exaggerated startle response to noise. In retrospect, many parents recall that their baby had always been sensitive to loud noises.

The babies, who had been developing normally, now begin to lag behind. They still grow and develop, but the milestones all come a bit late. This is usually when parents start worrying that something is wrong.

They sometimes learn to sit up or even stand; they may begin to speak several words. But for these babies this is the pinnacle, the peak.

By 12 to 16 months, when most parents of other children are celebrating achievement, these parents are grieving loss. By now their babies have usually lost the ability to stand, to sit, and even to vocalize.

From there, the deterioration is relentless. Seizures typically begin in the second year. Before long, the toddler is completely blind and non-communicative. Progressive spasticity is interrupted by convulsions. The spasticity gives way only as the muscles completely atrophy. Paralysis sets in. Many can’t even swallow.

Even with the best of care, most have died by the time their peers are skipping off to kindergarten. Death usually comes from progressive paralysis, causing aspiration and recurrent pneumonias.

Far less common is the juvenile form of Tay-Sachs (described in greater detail below). Here, children appear normal until middle childhood. Clumsiness is the usually the first sign, but this is often dismissed until it can?t be ignored. Coordination continues to slip away even as uncontrolled, unwanted movements begin. Children lose the ability to speak while they are still grappling with their loss, often before the seizures begin. Eyesight darkens very gradually. Most die before their peers have gotten their driver’s licenses.

Even rarer is the adult form, which doesn?t begin until the twenties or thirties.

How is the disease transmitted?
Only through heredity. A Tay-Sachs carrier has one normal gene for production of the Hex-A enzyme and one Tay-Sachs gene. The carrier does not have the illness and leads a normal, healthy and full life. However, when two carriers become parents: There is a one-in-four chance that any child they have will inherit a Tay-Sachs gene from each parent and have the disease. There is a one-in-four chance that the child will inherit the normal gene from each parent and be completely free of the disease and the Tay-Sachs gene. There is a two-in-four chance that the child will inherit one of each kind of gene and be a carrier like the parents and free of disease. If only one parent is a carrier, none of their children can have the disease, but each child has a 50-50 chance of inheriting the Tay-Sachs gene and being a carrier.

Who is at risk?
Tay-Sachs carriers are found most frequently among families of eastern European Jewish descent (Ashkenazi Jews). In the United States today, approximately one in every 27 Jews is a Tay-Sachs carrier.

Among Jews of Mediterranean (Sephardic) origin and in the general, non-Jewish population, the carrier rate is about one in 250. There are certain exceptions. French-Canadians and the Cajun community of Louisiana have the same carrier rate as Ashkenazi Jews, one in 27. Also, individuals with ancestry from Ireland are at increased risk for the Tay-Sachs gene. Current research indicates that among Irish Americans, the carrier rate is about one in 50.

All couples planning to have children should carefully consider their ancestry to evaluate the risk of each partner. Any person who can trace his or her lineage to a high-risk population should be tested. In addition, close relatives of carriers (children, sisters, brothers, cousins, aunts, uncles) must be tested since they may also be carriers.

How do you know if you’re a Tay-Sachs carrier?
The answer is a simple blood test.

The Tay-Sachs blood test, referred to as carrier screening, identifies Tay-Sachs carriers and non-carriers. It is urgent to understand that the Tay-Sachs gene gets passed from one generation to the next. Without carrier screening, it can remain hidden in a family for decades, surfacing unexpectedly and tragically with the birth of an affected child. The fact that there is no family history of Tay-Sachs disease does not lower an individual’s risk of being a carrier. It may simply be a lucky accident that, thus far, no child inherited a pair of Tay-Sachs genes.

Very often, Tay-Sachs testing is not included in routine health care. To be safe, remember to discuss testing with your health care provider.

The routine Tay-Sachs screen is an enzyme assay: a biochemical test that measures the level of Hex-A in a person’s blood. Carriers have less Hex-A in their body fluid and cells than non-carriers. Affected infants have almost none. A second type of screening is a DNA-based carrier test, which looks for specific mutations in the gene that codes for Hex-A.

Is there any treatment for Tay-Sachs?
Tragically, there is no cure, and no treatment that will prevent the disease from running its course. Affected children can only be made as comfortable as possible.

However, over the past several years, there has been a great deal of interest in the utility of Stem Cell Transplantation in infants with Tay-Sachs Disease. This procedure is still considered experimental, and there is no long-term data on outcomes. However, it appears that Stem Cell Transplants may slow or even arrest the progression of the disease process. However, by the time most children are diagnosed, the severity of brain damage that has already occurred is quite significant, as it begins long before birth. There is no evidence yet that Stem Cells can reverse such damage. As such, the most compelling results have been seen in the very few cases where the child was diagnosed before birth and the transplantation occurred in the immediate post-natal period.

Can Tay-Sachs Disease be diagnosed before birth?
Yes. Prenatal tests called amniocentesis and chorionic villus sampling (CVS) can diagnose Tay-Sachs before birth. If prenatal testing shows that Hex-A is present, the baby will not have Tay-Sachs. If it is missing, he or she will be affected. In unusual cases, DNA-based genetic testing can determine whether the fetus has infantile Tay-Sachs or another Hex-A deficiency and, possibly, how severely affected the baby will be.

Is there a “safe” way for a 2 carriers of the Tay-Sachs gene to have children?
Family planning approaches for carrier-couples now include pre-implantation genetic diagnosis, using in vitro fertilization (with genetic testing of the embryos, so that only healthy ones are implanted in the mother). This offers great hope to at-risk families wishing to have children. This also underscores the importance of Tay-Sachs carrier screening before pregnancy occurs.

Are there other forms of Tay-Sachs Disease besides the classical type that affects babies?
The classic infantile type of Tay-Sachs is the most common. However, there are other rare deficiencies of the Hex-A enzyme that sometimes are included under the name of Tay-Sachs disease. These often are referred to as juvenile, chronic and adult-onset forms of Hex-A deficiency. Affected individuals have low levels of the Hex-A enzyme that is missing entirely in the classical, infantile form. This may help explain why symptoms begin later in life and, generally, are less profound than in the classical, infantile Tay-Sachs disease. Children with juvenile Hex-A deficiency develop symptoms between the ages of 2 and 5 that resemble those of the classical, infantile form. Although the course of the disease is slower, death generally occurs by age 15. Symptoms of chronic Hex-A deficiency also may begin by age 5, but are far milder than those that characterize the infantile and juvenile forms. Mental abilities, vision and hearing remain intact; but there may be slurred speech, muscle weakness, muscle cramps, tremors, unsteady gait and, sometimes, mental illness. Individuals with adult-onset (aka ?late-onset Tay-Sachs?) Hex-A deficiency experience many of the same symptoms as individuals with the chronic form, but the symptoms begin later in life.