Tay-Sachs Disease

Clinical Characteristics
Ocular Features: 

Retinal ganglion cells become dysfunctional as a result of the toxic accumulation of intra-lysosomal GM2 ganglioside molecules causing early visual symptoms.  These cells in high density around the fovea centralis create a grayish-white appearance.  Since ganglion cells are absent in the foveolar region, this area retains the normal reddish appearance, producing the cherry-red spot.  Axonal decay and loss of the ganglion cells leads to optic atrophy and blindness.

Systemic Features: 

Sandoff disease may be clinically indistinguishable from Tay-Sachs disease even though the same enzyme is defective (albeit in separate subunits A and B that together comprise the functional hexosaminidase enzyme).   The infantile form of this lysosomal storage disease is the most common.  Infants appear to be normal until about 3-6 months of age when neurological development slows and muscles become weak.  Seizures, loss of interest, and progressive paralysis begin after this together with loss of vision and hearing.  The facies are coarse and the tongue is enlarged.  An exaggerated startle response is considered an early and helpful sign in the diagnosis.  Hepatosplenomegaly is usually not present.  Among infants with early onset disease, death usually occurs by 3 or 4 years of age.     

Ataxia with spinocerebellar degeneration, motor neuron disease, and progressive dystonia are more common in individuals with later onset of neurodegeneration.  The juvenile and adult-onset forms of the disease also progress more slowly.


Tay-Sachs disease is an autosomal recessive disorder caused by mutations in the hexosaminidase A gene, HEXA, (15q23-q24).  The altered enzyme is unable to break down GM2 ganglioside which accumulates in lysosomes and leads to neuronal death.

A related form, clinically and biochemically similar to Tay-Sachs disease , is GM2-gangliosidosis (272750) but it is caused by mutations in GM2A (5q31.3-q33.1) with normal hexosaminidase A and B.  Sandhoff disease (268800) is clinically indistinguishable but caused by mutations in the beta subunit of hexosaminidase (HEXB) A and B at 5q13. 

Autosomal recessive
Treatment Options: 

Treatment is largely supportive.  Anticonvulsant pharmaceuticals may help in the control of seizures but require frequent modifications as the neuronal degeneration progresses.  Airways and nutrition maintainence are important.

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


Article Title: 

Tay-Sachs disease

Fernandes Filho JA, Shapiro BE. Tay-Sachs disease. Arch Neurol. 2004 Sep;61(9):1466-8. Review.

PubMed ID: 
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