What is Tay-Sachs disease?

What is Tay-Sachs disease?

Tay-Sachs disease (the most severe form of Hexosaminidase A deficiency) is a progressive, fatal genetic condition that affects the nerve cells in the brain. People with Tay-Sachs lack a specific protein (enzyme) called hexosaminidase A. This enzyme deficiency causes a fatty substance, GM2 ganglioside, to build up in the brain. It is this accumulation that causes the symptoms of Tay-Sachs.

What causes Tay-Sachs disease?

All people have two copies of the Tay-Sachs gene (HEXA). Tay-Sachs occurs when neither of a person’s HEXA genes is working properly because of a mutation (harmful change). If a person has one working copy of the HEXA gene and the other copy has a mutation in it, he/she is called a “carrier.” Carriers don’t show symptoms but when two carriers have children together each child (boy or girl) will have a 25% (1/4) chance of developing Tay-Sachs. If only one parent passes on the defective gene to the child (50% chance in each pregnancy), the child will not develop the disease but will be a carrier and have the potential to pass the disease on to his or her children.

Although anyone can be a carrier of Tay-Sachs disease, the disease is much more common among people of Ashkenazi (Eastern European) Jewish descent. One in every 30 people of Ashkenazi Jewish descent is a carrier. Other populations with as many (or more) carriers include French Canadians, Cajuns (from Louisiana) and Old Order Amish in Pennsylvania. Some studies state that people of Irish ancestry have a 1 in 50 chance of being a carrier. Around 1 in every 300 people who are not of these backgrounds is a carrier for Tay-Sachs.

What are the symptoms of Tay-Sachs disease?

Symptoms of Tay-Sachs usually develop around 3-6 months of age when the child starts to have muscle weakness, low muscle tone, an increased startle response and sudden contractions of large muscles when falling asleep (myoclonic jerks).

Between 6 and 10 months of age, a child will not meet motor milestones and may lose the ability to perform tasks (such as sitting) that he/she had previously learned. Decreased eye movement and contact as well as attentiveness are also seen along with a specific change in the eye called a cherry-red spot which can be seen during an eye exam.

After 8 to 10 months of age, a baby will move less and become less responsive. Vision will be lost and many will have seizures by a year of age. A person’s head size will start to grow around 18 months of age and when a child is 2 years old, they typically have trouble swallowing and progress into an unresponsive vegetative state. Age of death is usually between 2 and 4 years, often from pneumonia.

In addition to classic Tay-Sachs, there are other forms of Hexosaminidase A deficiency that are sometimes referred to as forms of Tay-Sachs:

  • Juvenile Hexosaminidase A deficiency begins with trouble walking (ataxia) and incoordination in early childhood. Symptoms are similar to those of classic Tay-Sachs although the cherry-red spot is not as common. Age of death is usually in teenage years, usually from infections, although some will die much sooner.
  • Chronic Hexosaminidase A deficiency usually develops before age 10 but people do not lose as many motor skills as those with Tay-Sachs. Cognitive and verbal skills are affected later in the course.
  • Adult-onset Hexosaminidase A deficiency causes slow but progressive muscle weakness and wasting as well as trouble speaking clearly, cognitive problems, and dementia. Up to 40% of people have psychiatric problems (which can be present without dementia). Severity, even within a family, is very variable. Life expectancy can vary widely and may not be shortened.