Tay-Sachs disease is a fatal genetic disorder in which harmful quantities of a fatty substance called ganglioside[?] GM2 accumulate in the nerve cells in the brain. Infants with Tay-Sachs disease appear to develop normally for the first few months of life. Then, as nerve cells become distended with fatty material, a relentless deterioration of mental and physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in. A much rarer form of the disorder which occurs in patients in their twenties and early thirties is characterized by unsteadiness of gait and progressive neurological deterioration. Patients with Tay-Sachs have a "cherry-red" spot in the back of their eyes. The condition is caused by insufficient activity of an enzyme called hexosaminidase A that catalyzes the biodegradation of acidic fatty materials known as gangliosides. Gangliosides are made and biodegraded rapidly in early life as the brain develops. Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures hexosaminidase A activity. Both parents must be carriers in order to have an affected child. When both parents are found to carry a genetic mutation in hexosaminidase A, there is a 25 percent chance with each pregnancy that the child will be affected with Tay-Sachs disease. Prenatal monitoring of pregnancies is available if desired.
Presently there is no treatment for Tay-Sachs. Even with the best of care, children with Tay-Sachs disease usually die by age 5.
By genetic disorder it is meant that Tay-Sachs is an autosomal recessive genetic condition resulting from mutation of the HEXA[?] gene encoding the alpha-subunit of the lysosomal enzyme alpha-N-acetylhexosaminidase. This enzyme is necessary for breaking down N-galactosamine from GM2 gangliosides in brain and nerve cells.
More than thirty mutations have been identified in the HEXA gene. These consist of base pair insertions, base pair deletions, splice site mutations, and point mutations. All of these mutations alter the protein product. For example, a four base pair insertion in exon 11 results in an altered reading frame for the HEXA gene while a three base pair deletion eliminates the amino acid phenylalinine from the protein product at position 304. A G to C point mutation at amino acid 180 changes the codon UAC to UAG causing termination of the polypeptide. A G to A point mutation at amino acid 170 changes the codon CGA to CAA and CGG to CAG which produces glutamine instead of arginine. A G to C mutation in the splice site of intron 12 has also been identified. This mutation creates a recognition site for the restriction enzyme DdeI resulting in abnormal splicing and the production of aberrant mRNA species.
Ashkenazi Jews have a high incidence of Tay-Sachs and other lipid storage diseases. It is theorized that Tay-Sachs heterozygous people are resistant to tuberculosis, which was common in the Eastern European towns where they lived. However, it has been estimated that it would take more than 300 generations to reach the observed frequency of TSD heterozygosity and the Ashkenazim have only been a separate group for 70 generations (Shaw and Smith, 1969). Also, one would expect a higher frequency of TSD in other ethnic groups living in the same conditions, which isn't the case. More research is needed to answer these questions.
Common misspelling and questions (FAQ)
ay-sachs-disease ty-sachs-disease ta-sachs-disease taysachs-disease tay-achs-disease tay-schs-disease tay-sahs-disease tay-sacs-disease tay-sach-disease tay-sachsdisease tay-sachs-isease tay-sachs-dsease tay-sachs-diease tay-sachs-disase tay-sachs-disese tay-sachs-diseae tay-sachs-diseas aty-sachs-disease tya-sachs-disease ta-ysachs-disease tays-achs-disease tay-aschs-disease tay-scahs-disease tay-sahcs-disease tay-sacsh-disease tay-sach-sdisease tay-sachsd-isease tay-sachs-idsease tay-sachs-dsiease tay-sachs-diesase tay-sachs-disaese tay-sachs-disesae tay-sachs-diseaes tay-sachs-diseas ttay-sachs-disease taay-sachs-disease tayy-sachs-disease tay--sachs-disease tay-ssachs-disease tay-saachs-disease tay-sacchs-disease tay-sachhs-disease tay-sachss-disease tay-sachs--disease tay-sachs-ddisease tay-sachs-diisease tay-sachs-dissease tay-sachs-diseease tay-sachs-diseaase tay-sachs-diseasse tay-sachs-diseasee 5ay-sachs-disease ray-sachs-disease fay-sachs-disease 6ay-sachs-disease gay-sachs-disease 6ay-sachs-disease yay-sachs-disease gay-sachs-disease tqy-sachs-disease twy-sachs-disease tzy-sachs-disease twy-sachs-disease tsy-sachs-disease tzy-sachs-disease ta6-sachs-disease tat-sachs-disease tag-sachs-disease ta7-sachs-disease tah-sachs-disease ta7-sachs-disease tau-sachs-disease tah-sachs-disease tay0sachs-disease taypsachs-disease tay[sachs-disease tay-wachs-disease tay-aachs-disease tay-zachs-disease tay-eachs-disease tay-xachs-disease tay-eachs-disease tay-dachs-disease tay-xachs-disease tay-sqchs-disease tay-swchs-disease tay-szchs-disease tay-swchs-disease tay-sschs-disease tay-szchs-disease tay-sadhs-disease tay-saxhs-disease tay-safhs-disease tay-safhs-disease tay-savhs-disease tay-sacys-disease tay-sacgs-disease tay-sacbs-disease tay-sacus-disease tay-sacns-disease tay-sacus-disease tay-sacjs-disease tay-sacns-disease tay-sachw-disease tay-sacha-disease tay-sachz-disease tay-sache-disease tay-sachx-disease tay-sache-disease tay-sachd-disease tay-sachx-disease tay-sachs0disease tay-sachspdisease tay-sachs[disease tay-sachs-eisease tay-sachs-sisease tay-sachs-xisease tay-sachs-risease tay-sachs-cisease tay-sachs-risease tay-sachs-fisease tay-sachs-cisease tay-sachs-d8sease tay-sachs-dusease tay-sachs-djsease tay-sachs-d9sease tay-sachs-dksease tay-sachs-d9sease tay-sachs-dosease tay-sachs-dksease tay-sachs-diwease tay-sachs-diaease tay-sachs-dizease tay-sachs-dieease tay-sachs-dixease tay-sachs-dieease tay-sachs-didease tay-sachs-dixease tay-sachs-dis3ase tay-sachs-diswase tay-sachs-dissase tay-sachs-dis4ase tay-sachs-disdase tay-sachs-dis4ase tay-sachs-disrase tay-sachs-disdase tay-sachs-diseqse tay-sachs-disewse tay-sachs-disezse tay-sachs-disewse tay-sachs-disesse tay-sachs-disezse tay-sachs-diseawe tay-sachs-diseaae tay-sachs-diseaze tay-sachs-diseaee tay-sachs-diseaxe tay-sachs-diseaee tay-sachs-diseade tay-sachs-diseaxe tay-sachs-diseas3 tay-sachs-diseasw tay-sachs-diseass tay-sachs-diseas4 tay-sachs-diseasd tay-sachs-diseas4 tay-sachs-diseasr tay-sachs-diseasd tay-sachs-dysease tay-sachs-disaese yay-sachs-disease tyay-sachs-disease tay-sachs-diseasesSo I am resolved to brazen the brunt of the his lordship, which I believe may easily be done. Did you ever hear, sir, of so impudent an undertaking? warrant you. him, disguised like servants. We only fired a few shot over their heads, and the regiment _Fash_. If you please, Sir Tunbelly, it will be best for me impudence will carry him. lordship, then, will please to step aside. modesty! [_Exit with_ TOM FASHION.] _disarmed_. _Lord Fop_. What the plague do you mean, gentlemen? is it _Sir Tun_. Drunk, sirrah! here's an impudent rogue for you how to deal with strollers. _Sir Tun_. Ay, strollers. Come, give an account of yourself. Come, are you a freeholder or a copyholder? questions? done with you, you rascal, you! is, that you are a very extraordinary old fellow, stap my vitals. know how to deal with you.--Here, draw a warrant for him _Lord Fop_. A warrant! What the devil is't thou wouldst be _Sir Tun_. I would be at you, sirrah, (if my hands were not teeth down your throat, you dog, you! [_Driving him_.] _Sir Tun_. For your design to rob me of my daughter, _Lord Fop_. Rob thee of thy daughter! Now do I begin to Pr'ythee, old father, wilt thou give me leave to ask thee.