Tay Sachs and how the defect in the gene

causes the disease

Tay-Sachs disease is a rare and deadly Autosomal Recessive Disease that gradually destroys

the nervous system. It is developed when the body lacks one of the two forms of

Hexosaminidase, Hex-A. This is a protein that helps break down a chemical found in nerve

tissue called Gangliosides, particularly Ganglioside GM2. These build up in cells, especially

nerve cells in the brain consisting largely of ceramide and sugars. Hex-A possesses a and b

subunits and both subunits code for Chromosome 15 and 5 respectively.

(http://www.nhs.uk/conditions/Tay-Sachs-disease/Pages/Introduction.aspx.).

Tay-Sachs disease is said to be caused by a defective gene on chromosome 15. The altered a

chains shows a decrease in activity and stability. As such screening for Tay-Sachs disease is

recommended for people in high-risk groups namely European (Ashkenazi) Jewish origin,

US/Canada – 1 in 3-6,000 (1 in 550,000 - non Jews), Heterozygotes – 1 in 30- 40 (Jews), 1 in

300 - 400 others and also in Quebec, Amish population- Founder effect.

Ashkenazi patients possess no a chains due to defective mRNA splicing while French

Canadians contain no a chains due to deletion at the end of gene.

Screening fortunately can occur at two points, either before or after a baby is conceived. These

screening methods are described as:

Preconception Screening – where potential parents are able to check whether they carry the

Hex-A mutation before starting a family

Antenatal Screening - where a fetus is checked to see whether two copies of the HEXA

mutation have been inherited, which would cause Tay-Sachs disease to develop.

Tay-Sachs has been classified into Infantile, Juvenile, and Adult forms, depending on the

symptoms and when they first appear. Most people show the infantile form where the nerve

damage usually begins while the baby is still in the womb. Symptoms usually only appear
when the child is 3 to 6 months old. The disease tends to rapidly worsen causing death by Age

4. The Adult Form, Late-onset Tay-Sachs disease is however usually very rare.

Symptoms include Deafness, Decreased eye contact, Blindness, Decreased muscle tone (loss

of muscle strength), Delayed mental and Social Skills, Dementia, Increased startle reaction,

Irritability, Listlessness, Loss of motor skills, Paralysis or loss of muscle function, Seizures

and Slow growth. Tests include Patient Family History Taking, Enzyme analysis of blood or

body tissue for hexosaminidase levels and Eye examination which usually reveals a cherry-red

spot in the macula. (http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002390/)

Unfortunately there is no treatment for Tay-Sachs disease itself, only ways to make the patient

more comfortable.
 References

Tay-Sachs Disease. (Last reviewed: November 17, 2010) Retrieved on September 24, 2012,

from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002390/

Tay-Sachs Disease. (Last reviewed: 23/06/2011). Retrieved on September 24, 2012, from

http://www.nhs.uk/conditions/Tay-Sachs-disease/Pages/Introduction.aspx