Tay-Sachs Disease

Symptoms and Causes

What causes Tay-Sachs disease?

Tay-Sachs comes from a disease-causing variant (change) to the HEXA gene. Each baby has two copies of the HEXA gene, one from their biological father and one from their biological mother.

Tay-Sachs happens when both parents had a variant HEXA gene and passed it on. That means neither copy of the baby’s HEXA gene works well. Healthcare providers call this hexosaminidase A deficiency, or hex A deficiency.

What does it mean to be a Tay-Sachs carrier?

A carrier has one working copy of the HEXA gene and one copy with a disease-causing variant. Carriers don’t have the disease or show symptoms, since their bodies can rely on the working gene. But if two carriers have children together, there’s a:

• 25% (1 in 4) chance that the child won’t inherit any variant HEXA genes. The child won’t have Tay-Sachs or be a carrier.
• 50% (1 in 2) chance that the child gets a variant gene from one parent. When this happens, the child will be a carrier but won’t have Tay-Sachs. Since they’re a carrier, they may pass it to their children.
• 25% (1 in 4) chance that the child gets a variant gene from both parents. In this case, the child has Tay-Sachs disease.

What are typical symptoms of Tay-Sachs disease?

Symptoms of the most common form of Tay-Sachs start developing when babies are around 3 to 6 months old. The symptoms continue to progress as the child gets older. Children often don’t meet theirdevelopmental milestones.

Symptoms at 3 to 6 months:

• Increased startle response.
• Low muscle tone.
• Muscle weakness.
• Sudden contractions of large muscles when falling asleep, called myoclonic jerks.

Symptoms at 6 to 10 months:

• Decreased eye movement and eye contact.
• Lack of attentiveness.
• Losing ability to do tasks they could do before, such as sitting.
• Not meeting motor milestones (sitting up on their own, pulling up to standing, picking up objects with all their fingers).
• Cherry-red spot in the eye, which providers can see during an eye exam.

Symptoms at 8 to 10 months:

• Less movement.
• Less responsiveness.
• Loss of vision.
• Start ofseizures.

At around a year and a half (18 months), the child’s head size starts to grow. When they’re 2 years old, they often have trouble swallowing. They may end up in anunresponsive state. This means they don’t have much brain function. Age of death is usually between 2 and 4 years old. Pneumonia is often the cause of death.

How do other forms of Tay-Sachs progress?

Less often, someone may have another form of Tay-Sachs, also caused by a hexosaminidase A deficiency. These other forms progress differently and may include additional symptoms:

Juvenile hexosaminidase A deficiency:

• Symptoms develop later than classic infantile Tay-Sachs, usually after age 2.
• Children haveataxia(trouble walking) and lack of coordination.
• Other symptoms are like classic Tay-Sachs, though the cherry-red spot in the eye is less common.
• Children may live to the teenage years.

Chronic hexosaminidase A deficiency:

• This condition usually develops before age 10.
• Children don’t lose as many motor skills as with classic Tay-Sachs.
• It affects cognitive and verbal skills later in the course of the disease.
• Children may live to their late teenage years.

Late-onset hexosaminidase A deficiency:

• People with this condition experience slow but progressive muscle weakness and wasting.
• They may also have trouble speaking clearly, problems with thinking, memory and concentration, anddementia.
• Up to 40% of people have psychiatric problems, even if they don’t have dementia.
• Life expectancy varies widely. Some people live a typical life span.