Tay-Sachs Disease

🧠 Tay-Sachs Disease

Overview

Tay-Sachs disease is a rare, inherited genetic disorder that destroys nerve cells (neurons) in the brain and spinal cord. It is most commonly seen in infants, though rarer juvenile and adult-onset forms also exist.

🧬 Cause

• Tay-Sachs is caused by a mutation in the HEXA gene on chromosome 15.
• The HEXA gene makes part of an enzyme called beta-hexosaminidase A, which helps break down a fatty substance called GM2 ganglioside.
• Without this enzyme, GM2 builds up in the brain, causing progressive damage to nerve cells.

🧬 Inheritance

• Tay-Sachs is autosomal recessive:
  • A child must inherit two defective copies of the HEXA gene (one from each parent) to have the disease.
  • Carriers (with one defective gene) have no symptoms.

🌍 Who Is Affected?

• Most common in:
  • Ashkenazi Jewish populations
  • French-Canadian, Cajun (Louisiana), and some Irish populations
• Occurs in about 1 in 320,000 live births (varies by population)

🧒 Symptoms

Infantile Tay-Sachs (most common and severe form)

• Symptoms appear at 3 to 6 months of age:
  • Loss of motor skills (e.g., turning over, sitting)
  • Exaggerated startle response
  • Weakness
  • Seizures
  • Vision and hearing loss
  • Paralysis
  • Cherry-red spot in the eye (seen on eye exam)
• Progression is rapid. Children usually become blind, deaf, and unable to move.
• Most children with the infantile form die by age 4–5.

Juvenile Tay-Sachs

• Onset between ages 2 and 10
• Slower progression but similar neurological symptoms
• Life expectancy: mid-teens to early adulthood

Adult/Late-Onset Tay-Sachs

• Very rare
• Milder symptoms: muscle weakness, coordination problems, psychiatric issues
• May not significantly shorten lifespan

🔬 Diagnosis

• Enzyme test: Measures beta-hexosaminidase A activity (very low or absent in affected individuals)
• Genetic testing: Confirms mutations in the HEXA gene
• Carrier screening: Especially recommended for individuals in high-risk populations

💊 Treatment

• No cure
• Treatment is supportive and palliative:
  • Seizure control
  • Nutritional support (feeding tubes in later stages)
  • Respiratory care
  • Physical therapy

Research and Experimental Approaches:

• Gene therapy and enzyme replacement therapy are in development but not yet widely available.
• Clinical trials are ongoing.

🧬 Prevention

• Carrier screening and genetic counseling are essential, especially in high-risk populations.
• Preimplantation genetic diagnosis (PGD) and prenatal testing are options for at-risk couples.

📘 Summary