Tay sachs disease

Tay-Sachs disease
Tay-sachsUMich.jpg
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Developmental delay, muscle weakness, seizures, vision and hearing loss
Complications	N/A
Onset	Infancy
Duration	Progressive
Types	N/A
Causes	Genetic mutation in the HEXA gene
Risks	Ashkenazi Jewish descent, French-Canadian descent
Diagnosis	Genetic testing, enzyme assay
Differential diagnosis	N/A
Prevention	N/A
Treatment	Supportive care
Medication	N/A
Prognosis	Poor
Frequency	Rare
Deaths	N/A

Autorecessive Tay Sachs

Tay-Sachs disease is a rare, inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. It is a type of lysosomal storage disorder caused by a deficiency of the enzyme hexosaminidase A.

Etiology

Tay-Sachs disease is caused by mutations in the HEXA gene, which provides instructions for making a part of the enzyme beta-hexosaminidase A. This enzyme is located in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. When beta-hexosaminidase A is absent or not functioning properly, a fatty substance called GM2 ganglioside accumulates to toxic levels, particularly in nerve cells in the brain and spinal cord.

Epidemiology

Tay-Sachs disease is most common in people of Ashkenazi Jewish descent, with a carrier frequency of approximately 1 in 27. It is also more prevalent in certain French-Canadian communities in Quebec, the Cajun population of Louisiana, and the Old Order Amish community in Pennsylvania.

Pathophysiology

The accumulation of GM2 ganglioside in the neurons leads to progressive neurodegeneration. The buildup of this lipid interferes with normal biological processes, causing the neurons to become dysfunctional and eventually die. This neuronal death leads to the symptoms observed in Tay-Sachs disease.

Clinical Presentation

The classic form of Tay-Sachs disease presents in infancy. Affected infants typically appear normal until about 3 to 6 months of age, when their development slows and muscles used for movement weaken. Other symptoms include:

• Loss of motor skills
• Increased startle reaction
• Seizures
• Vision and hearing loss
• "Cherry-red" spot on the macula
• Muscle stiffness (spasticity)

Diagnosis

Diagnosis of Tay-Sachs disease is based on clinical symptoms, family history, and laboratory tests. The following tests are commonly used:

• Enzyme assay: Measures the activity of hexosaminidase A in blood or tissue samples.
• Genetic testing: Identifies mutations in the HEXA gene.
• Prenatal testing: Can be performed if there is a known risk of Tay-Sachs disease in the family.

Management

There is currently no cure for Tay-Sachs disease. Management focuses on supportive care to improve quality of life and may include:

• Anticonvulsants to manage seizures
• Physical therapy to maintain joint function
• Feeding tubes for nutrition
• Respiratory care to prevent infections

Prognosis

The prognosis for individuals with Tay-Sachs disease is poor. Children with the infantile form of the disease typically do not survive past early childhood. The disease progresses rapidly, leading to severe disability and early death.

Prevention

Carrier screening is available for individuals of high-risk populations, such as those of Ashkenazi Jewish descent. Genetic counseling is recommended for carriers and those with a family history of Tay-Sachs disease.

Research

Research is ongoing to find effective treatments for Tay-Sachs disease. Approaches being studied include gene therapy, enzyme replacement therapy, and substrate reduction therapy.

See also

• Lysosomal storage disorder
• Genetic disorder
• Neurodegenerative disease