Tay-Sachs Disease

The metabolism of sphingolipids (Figure 2) is very complicated and requires many enzymes. Although the occurrence of Sphingolipidoses is rare, many are possible due to the large number of different enzymes required. Absence of any one of these enzymes can impair the metabolism and result in a spingolipidose. Genetic mutation of a gene which codes for an enzyme means it is not produced and so this prevents the chain of reactions when one sphingolipid cannot be broken down into another, leading to a build-up of a specific substrate in cells.
Research has managed to show which enzymes are lacking for each disease: Tay-Sachs lacking hexosaminidase A, Niemann-Pick disease lacking sphingomyelinase, Fabry’s disease lacking alpha-galactosidase A, …show more content…
Tay-Sachs is an autosomal recessive trait, most common in the Eastern European Jewish community, with 1 in 30 as carriers. (Harvard Health Publications, 2013). This gene is the HEXA gene, located on chromosome 15, which carries the information for beta-hexosaminidase A. This enzyme is located in lysosomes and is responsible for breaking down GM2 ganglioside. (Figure 2). When no enzyme is present, as with Tay Sach’s, GM2 ganglioside will not be broken down (Figure 3). This leads to accumulation of GM2 ganglioside in neurons in the brain and spinal cord, and eventually results in the death of neurons. First symptoms can be seen around 6 months, as children’s cognitive and motor function deteriorates as the GM2 ganglioside accumulates, causing seizures, further disability and ultimately paralysis and death by the age of 5. There is currently no treatment available, and the only option is to screen potential carriers and offer genetic counselling. (Fong C.T. …show more content…
There have been over 70 mutations discovered that result in low levels of enzyme production. This enzyme degrades galactosylceramides (Figure 6) and without it, results in a large accumulation of psychosine. This results in the loss of Schwann cells and oligodendrocytes, which reduces the amount of myelin in the nervous system. It also can affect lipid rafts in the axons which causes axonal degradation in the central and peripheral nervous system. (Lee, W. C. et al, 2010)
There are 4 types of Krabbes disease, which are distinguished by age of onset. Type 1 affects young infants, 2 affects older infants, 3 affects teenagers and 4 affects adults. Psychosine builds up causing many symptoms including: irritability, crying, limb stiffness, feeding problems, seizures, fevers and slow mental development as axons are degraded, with patients often blind and very impaired towards the end stages. To patients suffering from Krabbes disease under the age of 2, it is fatal, however Type 3 and 4 are likely to live much longer and have a slower onset of symptoms. (Lopez-Rosas, A.

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