Tay–Sachs disease

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Tay–Sachs disease
Synonyms	GM2 gangliosidosis, hexosaminidase A deficiency
Pronounce
Specialty	Neurology, Genetics
Symptoms	Developmental delay, muscle weakness, seizures, vision loss, hearing loss
Complications	N/A
Onset	Infancy
Duration	Progressive
Types	Infantile, juvenile, adult/late-onset
Causes	Genetic mutation in the HEXA gene
Risks	Ashkenazi Jewish descent, French-Canadian descent, Cajun descent
Diagnosis	Genetic testing, enzyme assay
Differential diagnosis	Sandhoff disease, Niemann-Pick disease, Mucolipidosis
Prevention	Genetic counseling
Treatment	Supportive care
Medication
Prognosis	Poor, often fatal in early childhood
Frequency	1 in 320,000 overall, higher in certain populations
Deaths

Tay–Sachs disease is a rare autosomal recessive genetic disorder that results in the destruction of nerve cells (neurons) in the brain and spinal cord. The most common form of Tay–Sachs disease becomes apparent in infancy. Other forms of Tay–Sachs disease are very rare and occur in patients in their twenties and early thirties (juvenile Tay–Sachs disease) or during adulthood (late-onset Tay–Sachs disease).

Symptoms

The symptoms of Tay–Sachs disease vary depending on the form of the disease. In the most common infantile form, symptoms typically appear around six months of age and may include:

• Loss of motor skills
• Increased startle reaction
• Seizures
• Vision and hearing loss
• Intellectual disability
• Paralysis

Juvenile and adult forms of Tay–Sachs disease have a slower progression and may include symptoms such as:

• Muscle weakness
• Coordination problems
• Speech difficulties
• Mental illness

Cause

Tay–Sachs disease is caused by a mutation in the HEXA gene on chromosome 15. This gene encodes the alpha subunit of the enzyme beta-hexosaminidase A, which is necessary for breaking down a fatty substance called GM2 ganglioside. Without functional beta-hexosaminidase A, GM2 ganglioside accumulates to toxic levels, particularly in neurons, leading to the symptoms of Tay–Sachs disease.

Diagnosis

Diagnosis of Tay–Sachs disease typically involves:

• Genetic testing to identify mutations in the HEXA gene
• Enzyme assay to measure the activity of beta-hexosaminidase A
• Prenatal testing for at-risk pregnancies

Treatment

There is currently no cure for Tay–Sachs disease. Treatment focuses on managing symptoms and providing supportive care. This may include:

• Anticonvulsants for seizures
• Physical therapy to maintain mobility
• Nutritional support
• Respiratory care

Epidemiology

Tay–Sachs disease is more common in certain populations, including Ashkenazi Jews, French Canadians, and Cajuns from Louisiana. Carrier screening programs have significantly reduced the incidence of Tay–Sachs disease in these populations.

History

Tay–Sachs disease is named after Warren Tay, a British ophthalmologist who first described the characteristic red spot on the retina in 1881, and Bernard Sachs, an American neurologist who described the cellular changes and noted the increased prevalence in Ashkenazi Jews in 1887.

See also

• Genetic disorder
• Lysosomal storage disease
• Neurodegenerative disease
• HEXA gene
• GM2 ganglioside

See also

• Genetic testing
• Autosomal recessive
• Seizures
• Intellectual disability
• Physical therapy