The Hereditary Disease of Tay-Sachs Disease

The Hereditary Disease of Tay-Sachs Disease

Tay-Sachs disease is a rare hereditary disease found mainly in infants but is also found in juveniles and adults. It is caused by the abnormal metabolism of fats and is characterized by mental deterioration, blindness, and paralysis. There is no available treatment for this disease.

The ethnic group of Ashkenazi Jews, is very tightly knit. Their religion teaches them to remain among their own small group. Ashkenazi Jews rarely marry outside of their group. Ashkenazi Jews have a carrier frequency of 1 in 25. As Tay-Sachs disease is inherited as autosomal recessive traits, two carriers must breed in order to produce and offspring with Tay-Sachs. Because of the high carrier frequency in Ashkenazi Jews, they are considered to be 10 times more likely to have Tay-Sachs disease than the general population. Carrier screening is recommended pre-pregnancy in all couples in whom at least one is an Ashkenazi Jew.

Lysosomes contain hydrolytic enzymes which function in the acid of the lysosome and are meant to be secreted not as wastes into the extracellular fluids, but as secretory proteins into an intracellular organelle. When one of these enzymes is dysfunctional, the catabolism of its macromolecule does not completely occur and there is a buildup of the macromolecule inside the lysosome. This results in great numbers of large lysosomes which begin to interfere with the normal functions of the cell. This disorder is called lysosomal storage disorder. These disorders can eventually lead to the dysfunction of the organs. The organs affected by the disorder are determined by two factors: 1) The location in the body where the macromolecules that are to be catabolized are found, and 2) The location where the catabolism occurs.

Tay-Sachs disease is a form of these lysosomal storage diseases. It is scientifically known as GM2 gangliosidosis: Hexosaminidase alpha-subunit deficiency. Three polypeptides encoded by three separate locations on the chromosome are needed for the catabolism of GM2 gangliosides. When these genes are mutated, the result is a buildup of the glycosphingolipid GM2 gangliosides. Over 50 mutations have been identified. Tay-Sachs disease is the most common form of gangliosidosis and results from a mutation of the alpha-subunit location on chromosome 15. This causes a severe dysfunction in the enzyme hexosaminidase A.

Glycosphingolipids, otherwise known as GSLs, are components of the plasma membrane of eukaryotic cells.