Tay-Sachs Disease 2011

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Revision as of 15:47, 13 May 2011 by Uskat (talk | contribs) (Phenotype)


The Tay-Sachs disease (TSD) is a rare autosomal, recessive genetic disorder which is caused by accumulation of lipids in the brain. This leads to the cell death of those neurons. There exist three different variations of the TSD. The most common one is the Infantile Tay-Sachs disease which affects death of the children under the age of 5. The two other variants are the Juvenile and Adult/Late Onset TSD, which are less aggressive. The disease causes a deterioration of mental and physical abilities. Sadly, there currently exists no treatment.


Infantile Tay-Sachs disease:

The most common and aggressive form of TSD is the infantile TSD, which has a wide range of different symptoms and leads to the early death of the affected children. The most common symptoms are:

  • normal development in the first six month after birth
  • "cherry-red" macula
  • paralysis
  • dementia
  • blindness
  • deafness
  • muscle atrophy
  • startle response to sound stimuli
  • inability to coordinate muscle movement (child can't roll over and sit)
  • death in the second or third year

Juvenile and Adult TSD:

This forms of the Tay-Sachs disease occur later in lifetime. These two forms were not always recogniced as variants of the TSD. The symptomes of these forms are less aggressive. Often the patients become wheelchair users and have some psychiatric and physical limitation, which could be handled with drugs.


See also description of this disease in

Biochemical disease mechanism

The example protein is involved in the hydrolysis of terminal N--hexosamines. It is a heterodimer consisting one alpha subunit (encoded by HEXA) and one beta subunit (encoded by HEXB). The enzyme is responsible for the degradation of GM2 gangliosides (which are fatty acid derivatives) and other molecules in the brain and the tissue. More precisely the enzyme breaks down the phospholipids. If the enzyme is defect it leads to an accumulation of GM2 gangliosides in the neurons, which affect the death of those cells.



Only mutations in the HEXA gene can results in the TSD, whereas mutations in the HEXB gene results in other metabolic diseases. Nowadays, there are more then 120 mutations known, which cause the TSD disease. These mutations suppress the activity of the Hexosamidase A. This has as an effect that the break down of the GM2 gangliosides doesn't work anymore, which leads to the toxic accumulation of these. There is a strong prevalence for the TSD in the Eastern European Jewish, Cajuns and French Canadians. Most of the mutations in HEXA lead to the TSD, because they delete the enzyme function completely, which cause the infantile form of TSD. There are other mutations, which only reduce the enzyme-activity and therefore, cause the Juvenile or Adult TSD.

Reference sequence

Which sequence does not cause the disease and is most often found in the population.

Neutral mutations

Disease causing mutations