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Tay-Sachs Disease

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on September 2, 2009 at 11:51:56 pm
 

 Tay-Sachs Disease

 

Tay-Sachs disease is an autosomal recessive disorder. It is a mutation in the HEXA gene on the long arm of chromosome 15. It is common in the Ashkenazi-Jewish population, approximately 1:3600 births, with a carrier frequency of 1:30 (Young 2005) and a higher incidence among a number of other population groups. 

 

The HEXA gene encodes for β-Hexosaminidase A, an enzyme responsible for the breakdown of the fatty substance ganglioside GM2, which is found in the brain (Young 2005). This mutation of the HEXA gene causes an insufficiency in the concentration of this enzyme in the body of the affected person. This enzyme deficiency allows GM2 to build up in excess amounts in the lysosomes of the neural cells. This causes neuro-degeneration, resulting in a range of progressive symptoms. There are 3 types of Tay-Sachs; infant, juvenile and chronic adult-onset, with infant being most prevalent. 

 

Symptoms first appear in infants around the age 2-6 months, with normal development up until then. As it is a neurodegenerative disorder, the first symptoms are a decline in general motor skills and muscle weakness. It becomes difficult for the child to hold their head up, with many other problems presenting. These include blindness, poor feeding, lethargy, hypotonia (low pressure in the intraocular fluid), hyperreflexia (increased activity of the physiological reflexes), opisthotonos (a spasm of the muscles in which the head and lower limbs are thrust forward, and the spine is arched), hyperacusis (exceptional hearing), deafness, spasticity, myoclonic seizures. A major indicator of TS is a cherry red spot on the fovea centralis of the macula in the eye (Chen 2006). The spot indicates the destruction of ganglion cells in the foveal area, with the remaining cells filled with ganglioside (Chen 2006). 

 

  Cherry Red Spot

(The Internation Pathology Laboratory for Medical Education 2009)

 

The HEXA gene (15q23-q24) has been identified to have over 100 mutations to date (Chen 2006) in relation to Tay-Sachs. There are certain mutations associated with particular populations.In the case of the Ashkenazi Jews, there are two predominant mutations responsible for Tay-Sachs. There is 'a four base-pair insertion into exon 11 of the HEXA gene accounting for 75-80% of all mutations, and a splice site mutation in intron 12, accounting for 15%' (Chen 2006).

 

A simple blood test is able to detect levels of hexosaminidase activity in suspected cases. More intensive testing may also include CT scan or MRI of the brain. Prenatal diagnosis is also possible. Either a DNA analysis or an enzyme analysis to check for an absence of hexoasminidase activity in cultured amniocytes or chorionic villus cells (Chen 2006). As is it a genetic disorder, there are no treatments available. If a positive case is identified in-utero, there is the option of termination of the pregnancy. If the disease is identified after birth, the only option is to manage the condition as best as possible, to make the child comfortable for the remaining time.

 

If both parents are found to be carriers of the mutation, the risk of giving birth to an affected child is 25%. Options available to couples who find themselves in this situation include egg/sperm donation, preimplantation genetic diagnosis, and adoption. 

 

References:

Chen, H 2006, Atlas of Genetic Diagnosis and Counseling,1st edn, Humana Press Inc. New Jersey.

 

Filho, J Shapiro, B 2004, 'History of Neurology: Seminal Citation', Tay-Sachs Disease, vol 61 pp. 1466-1468

 

Myerowitz, R Costigan, C 1988, 'The Journal of Biological Chemistry', The major defect in Ashkenazi Jews with Tay-Sachs Disease is an insertion in the gene for the a-chain of B-Hexosaminidase, vol. 263, no. 35, pp. 18587-18589

 

Pierce, B 1990, The Family Genetic Sourcebook, Wiley, New York.

 

Emery, A Mueller, R 1992, Elements of Medical Genetics, 8th edn, Churchill Livingstone, Edinburgh, New York.

 

Young, I 2005, Medical Genetics, Oxford University Press, Oxford.

 

The Internation Pathology Laboratory for Medical Education, viewed 2 September 2009 <library.med.utah.edu/WebPath/COW/COW158.html>

 

 

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