Genetic disease tend to be higher in certain communities, many because they tend to procreate among themselves. This leads to persistence of the genetic aberration and increase in frequency. Tay-Sachs disease was described by Warren Tay and Bernard Sachs in the late 1800s.
The disease has many variants:
Genetic testing is advised in populations with a high incidence. Current tests identify up to 99% of carriers with low false negative rates. The activity of the enzyme can be determined suing enzyme analysis techniques. The test are very accurate but there may be limitations in pregnant women or women on contraceptives. Prenatal diagnosis may be done if both parents are known to be carriers via amniocentesis and the cell tested for the enzyme activity .
Imaging such as magnetic resonance imaging (MRI) of the brain may show generalised atrophy and cerebellar atrophy.
There is no treatment currently with a few trails of enzyme replacement but they have been unsuccessful. Treatment is supportive and includes nutrition and treatment of infections. Treatment of seizures and mental problems is difficult. Occupational and physical therapy may be useful. Counselling of the parents is essential due to the grave prognosis. Support groups are helpful for the family .
The accumulation of the GM2 ganglioside glycolipid is caused by a defect or absence of beta-hexosaminidase A, which is required for the degradation of the glycolipid. It is a single gene mutation and its mode of inheritance is autosomal recessive. The gene is found on chromosome 15. A lack of hexosaminidase A leads to accumulation of GM2 ganglioside which leads to the neurodegeneration. The enzyme activity can vary giving different variants of the disease. The worst having 0.1% normal activity .
The incidence in the normal population is 1 in every 360,000 as compared to Ashkenazi Jewish population where the incidence is 1 in every 3600, with carrier rates as high as 1 in 25. There is also a higher incidence in French Canadians and the Cajuns of Louisiana. Prenatal diagnosis has increased the rates of detection with carriers being identified, especially in these high risk groups .
The accumulation of the glycolipid leads to neurodegeneration, which can vary in its onset and is proportional to the speed at which the glycolipids accumulate within the neurons. There are no alternate pathways for its degradation thus the cell has no way of stopping its accumulation. The accumulation leads to neuronal cell dysfunction and ultimately cell death .
Genetic screening and counselling is essential for high risk communities, and if both parents are found to be carriers then prenatal diagnosis has to be made and decisions about the pregnancy discussed. This may even include termination of the pregnancy, but is dependent on the laws of the country/state   .
Tay-Sachs disease is a type of GM2 gangliosidoses, a lipid storage disease caused by mutations of the HEXA gene on chromosome 15 that lead to alteration of enzymes. Tay-Sachs disease is a variant and is caused by absence or defects of hexosaminidase A. Tay-Sachs disease is an autosomal recessive disease that causes excess storage of cell membrane glycolipid (GM2 ganglioside) within the lysosomes. This leads to accumulation within neuronal cells with their subsequent degeneration. The overall prognosis is poor, but screening tests have identified the carriers allowing for genetic counselling and prenatal testing .