Tay+Sachs+wiki-+kat

=Tay-Sachs Disorder- Kat McCabe=

What is it?
Tay-Sachs disorder is an inherited disorder in which nerve cells deteriorate and eventually die.
 * All problems associated with Tay-Sachs are caused by the protein hexosaminidase A (Hex A).
 * The protein has two parts an alpha and a beta subunits
 * There is an activator that can bind to the alpha and beta
 * Hex A is found in the lysosome of cells, specifically nerve cells.
 * Lysosomes are considered the recycling plants of cells, they break down complicated molecules so they can be reused
 * Hex A has a specific purpose--> to break down a large molecule called GM2 ganglioside, which is needed to make nerve cell membranes.
 * The activator subunits bring the GM2 molecule to the lysosome where it binds to the beta and alpha subunits.
 * The binding turns on Hex A and the GM2 molecule is processed into smaller component pieces to be used again.
 * **People with Tay- Sachs, their alpha subunit of Hex A is either missing, or does not work right.**
 * Hex A can no longer hold the GM2 ganglioside that is brought by the activator.
 * This means GM2 ganglioside can't be broken down and it accumulates in the lysosomes.
 * This causes the nerve cell to swell.
 * Because GM2 ganglioside can't be recycled, there ie limited repair or construction of new membrane
 * The build up is toxic to the cell!!!
 * **The alpha subunit of hexosaminisidase A is encoded by a gene called Hex A on chromosome 15.**
 * [[image:chromosome_15.jpg width="498" height="375"]]
 * There are about 90 mutations of this gene that can cause Tay-Sachs
 * __**Mutations that cause the most severe Tay-Sachs form, changes the DNA sequence so there is no protein. (Deletion)**__

How is it inherited?

 * Tay- Sachs is inherited, not contagious, a person gets it when they inherit TWO severe mutations in the HEX A genes. ONE from Each parent.
 * A child receives on chromosome from the dad and one from the mom, if both of the chromosomes have the mutation, then the child will develop Tay-Sachs. (25%)
 * **Tay-Sachs is a recessive disorder.**
 * The parents children can also be carriers if they have one of the mutated chromosomes.
 * Not all of the parents children will develop Tay-Sachs, some of the children may be carriers (50%) or one of the children may not be affected at all (25%).
 * [[image:tay-sachs_pedigree.jpg]]
 * Both parents have to be carriers for the child to develop Tay-Sachs as well.
 * 1 in every 27 Jewish people in America are thought to be carriers.
 * [[image:tay_sachs_punnet_square.jpg width="228" height="228"]]

How is it diagnosed?

 * Scientists have created a tester molecule that mimics natural ganglioside.
 * When either Hex A or Hex B breaks down the "artificial" molecule, one of the products of the reaction is flourescent.
 * Doctors can take blood sample from patient and see how strongly the blood glows.
 * This measures the concentration of Hex A or Hex B.
 * When heat is applied to the test tube, Hex A is inactivated and can only act with Hex B
 * **This gives th total concentration of both.**
 * Scientists can also take //blood tests to check DNA//.
 * A blood sample is taken and the DNA is isolated from the white blood cells.
 * The DNA is put into a gel slab and an electric current is applied.
 * The current pushes the DNA through the gel, smaller pieces go fast and large pieces go slow.
 * This can show scientists if you have Tay-Sachs.
 * [[image:DNA_gel_slabs.gif width="240" height="147"]]

How is it treated?

 * //**Enzyme Replacement Therapy**//
 * This replaces the enzyme thats missing, like insulin for people with diabetes.
 * Problem: the enzyme couldn't reach the brain.
 * The vessels in the brain have evolved and that vessels have very tight junctions so that toxic molecules can't get across and interfere with normal functions of the brain.
 * This therapy works well with non-neurological diseases like Goucheax disease.
 * //**Wheelchairs**// (not soo much a treatment, but helps people move around)
 * Wheelchairs are used for comfort if they have poor locomotion skills.
 * [[image:wheelchair.jpg width="269" height="248"]]
 * **//Gene Replacement Therapy//**
 * Scientists have to be able to put the gene in the neurons where the accumulation of GM2 ganglioside occurs.
 * More difficult than enzyme therapy.

What is it like to have it?

 * Symptoms are different for different ages of people who have Tay-Sachs.
 * **Babies with early onset Tay-Sachs**
 * [[image:tay_sachs_child.jpg width="312" height="235"]]
 * Show symptoms at about 6 months, don't have motor and mental skills
 * Usually become paralyzed and die at age 5.
 * **Juvenile Tay-Sachs**
 * [[image:child09.jpg width="188" height="253"]]
 * Symptoms show at age 5.
 * Symptoms are like early onset, but the progression of juvenile Tay-Sachs are slower.
 * **Adult Onset Tay-Sachs**
 * [[image:adult_with_tay_sachs.jpg]]
 * Starts later in life.
 * Symptoms include muscle weakness and cramp, slurred speech, and behavioral changes.