Tay-Sachs Disease

Background and History: 

Warren Tay, a British ophthalmologist, is believed to have described the first patient with this disorder in an oral presentation to his colleagues in 1881.  In 1887 an American physician and neurologist, Bernard Sachs, published an article in which he described the essential clinical features.

Clinical Correlations: 

Tay-Sachs disease is a neurodegenerative disorder in which cells of the nervous system become dysfunctional early in life.  The most common form of the disease is manifest in infants between the ages of 3 and 6 months.  Normal development slows and muscle weakness becomes evident.  Infants lose interest in their surroundings and gradually lose vision and hearing.  Blindness results from damage to the cells of the retina.  Seizures are common by one year of age and muscles lose their flexibility.  Progressive paralysis is often seen.  The ‘startle’ response to sounds is exaggerated and maintained longer than normal.  Eventually infants become nonresponsive.

Rarely both juveniles and adults develop a slightly different form of Tay-Sachs disease.  Progression of disease is slower in these individuals and they have somewhat different symptoms.

Genetics: 

This is an autosomal recessive disease in which two copies of the mutation are required for the disorder to be expressed.  The carrier parents with a single copy are clinically normal but each of their children has a 25% chance of inheriting both mutations from them and manifesting the symptoms.

This is a classical hereditary disorder in which a gene mutation produces an ineffective enzyme.  As a result, it is unable to break down certain molecules, which accumulate in tiny organelles in cells called lysosomes.  Being toxic to the cell, these accumulations cause cell death resulting in degeneration of, in this case, the nervous system.  Tay-Sachs disease is one of a number of such hereditary disorders known as lysosomal storage diseases.

Diagnosis and Prognosis: 

The diagnosis is often made by a pediatrician, neurologist, or ophthalmologist based on the clinical findings.  Gene testing can confirm the diagnosis.  Seizures can sometimes be treated with drugs for epilepsy but too often these are not completely effective.  Other treatment is largely supportive and death commonly occurs between the ages of 2 and 4 among individuals with early onset disease.

Application of gene therapy to fibroblast cell cultures have shown promise in restoring some hexosaminidase A function and may someday lead to human treatment. 

Additional Information