Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Tay-Sachs Disease

Sometimes called GM2 gangliosidosis.

What is Tay-Sachs Disease?

• Tay-Sachs disease is a genetic disorder characterized by the destruction of nerve cells in the spinal cord and brain
• Symptoms usually begin in infancy, but there are also juvenile and late-onset forms
  • The juvenile onset form is the rarest and onset occurs between two and ten years
  • Late onset form usually begins in the 30s and 40s and typically isn’t lethal
• Tay-Sachs disease is usually lethal
• Tay-Sachs disease is named after Waren Tay, a British ophthalmologist, and Bernard Sachs, and American neurologist
  • Tay identified the characteristic red spot on the retina, a sign of the disease, in 1881
  • Sachs described the cellular changes related to the disease and also recognized a higher prevalence of the disorder in Ashkenazi Jews
    • The rate of the disease in this population is 1 in 3,600
    • French Canadians of southeastern Quebec, the Cajuns of Louisiana, and the Old Order Amish of Pennsylvania also have Tay-Sachs disease at higher rates than the general population

How Do You Get It?

• Tay-Sachs disease is inherited in an autosomal recessive fashion, meaning that both parents must be carriers of the mutation in order for symptoms to appear
• The disease is caused by mutations of the HEXA gene, which is found on chromosome 15
  • Over 100 different mutations on this gene have been identified
  • These mutations disrupt the activity of the enzyme beta-N-acetylhexosaminidase A
  • This disruption causes GM2 ganglioside buildup in the nerve cells, which has a toxic effect and causes cell death

What Are the Symptoms?

• Symptoms of Tay-Sachs disease usually begin at around six months of age. Often the first sign is an unusually strong startle response, a reaction to sudden noises or other surprising stimuli. Other symptoms include:
  • Infantile
    • Listlessness
    • Muscle stiffness
    • Rapid decline of physical and mental abilities
      • Inability to swallow
      • Deafness
      • Blindness
      • Paralyzed
      • Atrophy
  • Juvenile
    • Mental and physical decline
    • Ataxia
    • Spasticity
    • Difficulty speaking
    • Difficulty swallowing
  • Late-Onset
    • Loss of neurological function
    • Unsteady gait
    • Difficulty speaking and swallowing
    • Spasticity
    • Psychiatric illness, sometimes resembling psychosis or schizophrenia
    • Cognitive decline
    • Loss of walking ability

How Is It Treated?

• There is no cure for Tay-Sachs disease, nor any treatment that can slow or stop progression of symptoms
• Supportive care can help extend lifespan and reduce the severity of symptoms
• Infants often require feeding tubes
• In the late onset variant, lithium can help treat psychiatric symptoms and seizures
• In the most common infantile form, the disease is usually lethal by age four; in the juvenile form, patients may survive to age 15; the late onset form is not lethal
• The is an urgent need for more effective treatments in Tay-Sachs disease
  • Gene therapy may be a promising future treatment
• Members of groups that are affected at higher rates may want to undergo genetic testing to determine if they are a carrier of the mutation in order to make informed decisions about child-rearing and family planning

Where Can I Learn More???

• Learn more about this disease from the Cure and Action for Tay-Sachs Foundation.
• Check out our cornerstone on this disease here.