Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord.The most common type, known as infantile Tay–Sachs disease, becomes apparent around three to six months of age with the baby losing the ability to turn over, sit, or crawl.This is then followed by seizures, hearing loss, and inability to move. Death usually occurs in early childhood. Less commonly the disease may occur in later childhood or adulthood. These forms are generally milder in nature.

Tay–Sachs disease is caused by a genetic mutation in the HEXA gene on chromosome 15. It is inherited from a person's parents in an autosomal recessive manner. The mutation results in problems with an enzyme called beta-hexosaminidase A which results in the buildup of the molecule GM2 ganglioside within cells, leading to toxicity. Diagnosis is by measuring the blood hexosaminidase A level or genetic testing. It is a type of GM2 gangliosidosis and a type of sphingolipidosis. The treatment of Tay–Sachs disease is supportive in nature. This may involve multiple specialities as well as psychosocial support for the family. The disease is rare in the general population. In Ashkenazi Jews, French Canadians of southeastern Quebec, and Cajuns of southern Louisiana, the condition is more common. Approximately 1 in 3,600 Ashkenazi Jews at birth are affected.

The disease is named after Waren Tay, who in 1881 first described a symptomatic red spot on the retina of the eye; and Bernard Sachs, who described in 1887 the cellular changes and noted an increased rate of disease in Ashkenazi Jews. Carriers of a single Tay–Sachs allele are typically normal. It has been hypothesized that being a carrier may confer protection from another condition such as tuberculosis, explaining the persistence of the allele in certain populations. Researchers are looking at gene therapy or enzyme replacement therapy as possible treatments.


Tay–Sachs disease is an autosomal recessive genetic disorder, meaning that when both parents are carriers, there is a 25% risk of giving birth to an affected child with each pregnancy. The affected child would have received a mutated copy of the gene from each parent. Tay–Sachs results from mutations in the HEXA gene on chromosome 15, which encodes the alphasubunit of beta-N-acetylhexosaminidase A, a lysosomal enzyme. By 2000, more than 100 different mutations had been identified in the human HEXA gene. These mutations have included single base insertions and deletions, splice phase mutations, missense mutations, and other more complex patterns. Each of these mutations alters the gene's protein product (i.e., the enzyme), sometimes severely inhibiting its function. In recent years, population studies and pedigree analysis have shown how such mutations arise and spread within small founder populations. Initial research focused on several such founder populations:

 Ashkenazi Jews. A four base pair insertion in exon 11 (1278insTATC) results in an altered reading frame for the HEXA gene. This mutation is the most prevalent mutation in the Ashkenazi Jewish population, and leads to the infantile form of Tay–Sachs disease.

 Cajuns. The same 1278insTATC mutation found among Ashkenazi Jews occurs in the Cajun population of southern Louisiana. Researchers have traced the ancestry of carriers from Louisiana families back to a single founder couple – not known to be Jewish – who lived in France in the 18th century.

 French Canadians. Two mutations, unrelated to the Ashkenazi/Cajun mutation, are absent in France but common among French Canadians living in eastern Quebec and Acadians from the Province of New Brunswick. Pedigree analysis suggests the mutations were uncommon before the late 17th century

In the 1960s and early 1970s, when the biochemical basis of Tay–Sachs disease was first becoming known, no mutations had been sequenced directly for genetic diseases. Researchers of that era did not yet know how common polymorphisms would prove to be. The "Jewish Fur Trader Hypothesis," with its implication that a single mutation must have spread from one population into another, reflected the knowledge at the time. Subsequent research, however, has proven that a large variety of different HEXA mutations can cause the disease. Because Tay– Sachs was one of the first genetic disorders for which widespread genetic screening was possible, it is one of the first genetic disorders in which the prevalence of compound heterozygosity has been demonstrated. Compound heterozygosity ultimately explains the disease's variability, including the late-onset forms. The disease can potentially result from the inheritance of two unrelated mutations in the HEXA gene, one from each parent. Classic infantile Tay–Sachs disease results when a child has inherited mutations from both parents that completely stop the biodegradation of gangliosides. Late onset forms occur due to the diverse mutation base – people with Tay–Sachs disease may technically be heterozygotes, with two differing HEXA mutations that both inactivate, alter, or inhibit enzyme activity. When a patient has at least one HEXA copy that still enables some level of hexosaminidase A activity, a later onset disease form occurs. When disease occurs because of two unrelated mutations, the patient is said to be a compound heterozygote. Heterozygous carriers (individuals who inherit one mutant allele) show abnormal enzyme activity but manifest no disease symptoms. This phenomenon is called dominance; the biochemical reason for wild-type alleles' dominance over nonfunctional mutant alleles in inborn errors of metabolism comes from how enzymes function. Enzymes are protein catalysts for chemical reactions; as catalysts, they speed up reactions without being used up in the process, so only small enzyme quantities are required to carry out a reaction. Someone homozygous for a nonfunctional mutation in the enzyme-encoding gene has little or no enzyme activity, so will manifest the abnormal phenotype. A heterozygote (heterozygous individual) has at least half of the normal enzyme activity level, due to expression of the wild-type allele. This level is normally enough to enable normal function and thus prevent phenotypic expression.


Tay–Sachs disease is typically first noticed in infants around 6 months old displaying an abnormally strong response to sudden noises or other stimuli, known as the "startle response". There may also be listlessness or muscle stiffness (hypertonia). The disease is classified into several forms, which are differentiated based on the onset age of neurological symptoms.


Three main approaches have been used to prevent or reduce the incidence of Tay–Sachs:

 Prenatal diagnosis. If both parents are identified as carriers, prenatal genetic testing can determine whether the fetus has inherited a defective gene copy from both parents. Chorionic villus sampling (CVS), the most common form of prenatal diagnosis, can be performed between 10 and 14 weeks of gestation. Amniocentesis is usually performed at 15–18 weeks. These procedures have risks of miscarriage of 1% or less.

 Preimplantation genetic diagnosis. By retrieving the mother's eggs for in vitro fertilization, it is possible to test the embryo for the disorder prior to implantation. Healthy embryos are then selected and transferred into the mother's womb, while unhealthy embryos are discarded. In addition to Tay–Sachs disease, preimplantation genetic diagnosis has been used to prevent cystic fibrosis and sickle cell anemia among other genetic disorders.

 Mate selection. In Orthodox Jewish circles, the organization Dor Yeshorim carries out an anonymous screening program so that carriers for Tay–Sachs and other genetic disorders can avoid marrying each other.


Enzyme Replacement Therapy
Enzyme replacement therapy techniques have been investigated for lysosomal storage disorders, and could potentially be used to treat Tay–Sachs as well. The goal would be to replace the nonfunctional enzyme, a process similar to insulin injections for diabetes. However, in previous studies, the HEXA enzyme itself has been thought to be too large to pass through the specialized cell layer in the blood vessels that forms the blood–brain barrier in humans. Researchers have also tried directly instilling the deficient enzyme hexosaminidase A into the cerebrospinal fluid (CSF) which bathes the brain. However, intracerebral neurons seem unable to take up this physically large molecule efficiently even when it is directly by them. Therefore, this approach to treatment of Tay–Sachs disease has also been ineffective so far.

Jacob Sheep Model
Tay–Sachs disease exists in Jacob sheep. The biochemical mechanism for this disease in the Jacob sheep is virtually identical to that in humans, wherein diminished activity of hexosaminidase A results in increased concentrations of GM2 ganglioside in the affected animal. Sequencing of the HEXA gene cDNA of affected Jacobs sheep reveal an identical number of nucleotides and exons as in the human HEXA gene, and 86% nucleotide sequence identity. A missense mutation (G444R) was found in the HEXA cDNA of the affected sheep. This mutation is a single nucleotide change at the end of exon 11, resulting in that exon's deletion (before translation) via splicing. The Tay– Sachs model provided by the Jacob sheep is the first to offer promise as a means for gene therapy clinical trials, which may prove useful for disease treatment in humans.

Substrate Reduction Therapy
Other experimental methods being researched involve substrate reduction therapy, which attempts to use alternative enzymes to increase the brain's catabolism of GM2 gangliosides to a point where residual degradative activity is sufficient to prevent substrate accumulation. One experiment has demonstrated that using the enzyme sialidase allows the genetic defect to be effectively bypassed, and as a consequence, GM2 gangliosides are metabolized so that their levels become almost inconsequential. If a safe pharmacological treatment can be developed – one that increases expression of lysosomal sialidase in neurons without other toxicity – then this new form of therapy could essentially cure the disease Another metabolic therapy under investigation for Tay–Sachs disease uses miglustat. This drug is a reversible inhibitor of the enzyme glucosylceramide synthase, which catalyses the first step in synthesizing glucose-based glycosphingolipids like GM2 ganglioside.

Increasing β-hexosaminidase A activity
As Tay–Sachs disease is a deficiency of β-hexosaminidase A, by getting a substance that increases its activity, people affected will not be deteriorating as fast or not at all. While for infantile Tay–Sachs disease, there is no β-hexosaminidase A so then the treatment would be ineffective. However, for people affected by Late-Onset Tay–Sachs disease, they still have β-hexosaminidase A. The drug pyrimethamine has been shown to increase activity of β-hexosaminidase A.However, the increased levels of β-hexosaminidase A still fall far short of the desired "10% of normal HEXA", above which the phenotypic symptoms begin to disappear.

Cord Blood Transplant
This is a highly invasive procedure which involves destroying the patient's blood system with chemotherapy and administering cord blood. Of five people who had received the treatment as of 2008, two were still alive after five years and they still had a great deal of health problems. Critics point to its harsh nature, and that it is unapproved. It is also hard for the blood to cross the blood–brain barrier, as well as very expensive, as each unit of cord blood costs $25,000 and adults need many units of cord blood.


Tay–Sachs disease is typically first noticed in infants around 6 months old displaying an abnormally strong response to sudden noises or other stimuli, known as the "startle response". There may also be listlessness or muscle stiffness (hypertonia). The disease is classified into several forms, which are differentiated based on the onset age of neurological symptoms.

Juvenile Tay–Sachs disease is rarer than other forms of Tay–Sachs, and usually is initially seen in children between two and ten years old. People with Tay–Sachs disease develop cognitive and motor skill deterioration, dysarthria, dysphagia, ataxia, and spasticity. Death usually occurs between the age of five to fifteen years.

A rare form of this disease, known as Adult-Onset or Late-Onset Tay–Sachs disease, usually has its first symptoms during the 30s or 40s. In contrast to the other forms, late-onset Tay–Sachs disease is usually not fatal as the effects can stop progressing. It is frequently misdiagnosed. It is characterized by unsteadiness of gait and progressive neurological deterioration. Symptoms of late-onset Tay–Sachs – which typically begin to be seen in adolescence or early adulthood – include speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness, particularly a schizophrenia-like psychosis. People with late-onset Tay–Sachs may become full-time wheelchair users in adulthood. Until the 1970s and 1980s, when the disease's molecular genetics became known, the juvenile and adult forms of the disease were not always recognized as variants of Tay–Sachs disease. Post-infantile Tay–Sachs was often misdiagnosed as another neurological disorder, such as Friedreich's ataxia.


1. "Tay–Sachs disease" (https://ghr.nlm.nih.gov/condition/tay-sachs-disease). Genetics Home Reference. October 2012. Archived (https://web.archive.org/web/20170513081001/https://ghr.nlm.nih.gov/condition/tay-sachs-disease) from the original on 13 May 2017. Retrieved 29 May 2017.

2. "Tay Sachs Disease" (https://rarediseases.org/rare-diseases/tay-sachs-disease/). NORD (National Organization for Rare Disorders). 2017. Archived (https://web.archive.org/web/20170220233334/https://rarediseases.org/rare-disea ses/tay-sachs-disease/) from the original on 20 February 2017. Retrieved 29 May 2017.

3. Marinetti, G. V. (2012). Disorders of Lipid Metabolism (https://books.google.com/books?id=t-ePBAAAQBAJ&pg=PA 205). Springer Science & Business Media. p. 205. ISBN 9781461595649. Archived (https://web.archive.org/web/20 171105195556/https://books.google.com/books?id=t-ePBAAAQBAJ&pg=PA205) from the original on 2017-11-05.

4. Walker, Julie (2007). Tay–Sachs Disease (https://books.google.com/books?id=fdA7LfGOai0C&pg=PA53). The Rosen Publishing Group. p. 53. ISBN 9781404206977. Archived (https://web.archive.org/web/20171105195556/htt ps://books.google.com/books?id=fdA7LfGOai0C&pg=PA53) from the original on 2017-11-05.

5. Vogel, Friedrich; Motulsky, Arno G. (2013). Vogel and Motulsky's Human Genetics: Problems and Approaches (http s://books.google.com/books?id=mbjtCAAAQBAJ&pg=PA578) (3 ed.). Springer Science & Business Media. p. 578. ISBN 9783662033562. Archived (https://web.archive.org/web/20171105195556/https://books.google.com/books?i d=mbjtCAAAQBAJ&pg=PA578) from the original on 2017-11-05.

6. "Tay–Sachs disease Information Page" (https://web.archive.org/web/20111127080325/http://www.ninds.nih.gov/dis orders/taysachs/taysachs.htm). National Institute of Neurological Disorders and Stroke. 14 February 2007. Archived from the original (http://www.ninds.nih.gov/disorders/taysachs/taysachs.htm) on 27 November 2011. Retrieved 10 May 2007.

7. McKusick, Victor A; Hamosh, Ada. "Online Mendelian Inheritance in Man" (http://omim.org/entry/272800). United States National Institutes of Health. Archived (https://web.archive.org/web/20160104022642/http://omim.org/entry/ 272800) from the original on 4 January 2016. Retrieved 24 April 2009.

8. Specola N, Vanier MT, Goutières F, Mikol J, Aicardi J (1 January 1990). "The juvenile and chronic forms of GM2 gangliosidosis: clinical and enzymatic heterogeneity". Neurology. 40 (1): 145–150. doi:10.1212/wnl.40.1.145 (http s://doi.org/10.1212%2Fwnl.40.1.145). PMID 2136940 (https://www.ncbi.nlm.nih.gov/pubmed/2136940).

9. Moe, P G; Benke, T A (2005). "Neurologic and Muscular Disorders". Current Pediatric Diagnosis and Treatment (17 ed.). McGraw-Hill. ISBN 978-0-07-142960-3.

10. Rosebush PI, MacQueen GM, Clarke JT, Callahan JW, Strasberg PM, Mazurek MF (1995). "Late-onset Tay–Sachs disease presenting as catatonic schizophrenia: Diagnostic and treatment issues". Journal of Clinical Psychiatry. 56 (8): 347–53. PMID 7635850 (https://www.ncbi.nlm.nih.gov/pubmed/7635850).

11. Willner JP, Grabowski GA, Gordon RE, Bender AN, Desnick RJ (July 1981). "Chronic GM2 gangliosidosis masquerading as atypical Friedreich's ataxia: Clinical, morphologic, and biochemical studies of nine cases". Neurology. 31 (7): 787–98. doi:10.1212/wnl.31.7.787 (https://doi.org/10.1212%2Fwnl.31.7.787). PMID 6454083 (ht tps://www.ncbi.nlm.nih.gov/pubmed/6454083).

12. Kaback MM (December 2000). "Population-based genetic screening for reproductive counseling: the Tay–Sachs disease model" (http://www.springerlink.com/content/we08hek03ka4fy5q/). European Journal of Pediatrics. 159 (Suppl 3): S192–S195. doi:10.1007/PL00014401 (https://doi.org/10.1007%2FPL00014401). ISSN 1432-1076 (http s://www.worldcat.org/issn/1432-1076). PMID 11216898 (https://www.ncbi.nlm.nih.gov/pubmed/11216898).

13. Myerowitz R (1997). "Tay–Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene". Human Mutation. 9 (3): 195–208. doi:10.1002/(SICI)1098-1004(1997)9:33.0.CO;2-7 (https://do i.org/10.1002%2F%28SICI%291098-1004%281997%299%3A3%3C195%3A%3AAID-HUMU1%3E3.0.CO%3B2- 7). PMID 9090523 (https://www.ncbi.nlm.nih.gov/pubmed/9090523).

14. Myerowitz R, Costigan FC (15 December 1988). "The major defect in Ashkenazi Jews with Tay–Sachs disease is an insertion in the gene for the alpha-chain of beta-hexosaminidase" (http://www.jbc.org/content/263/35/18587.abst ract). Journal of Biological Chemistry. 263 (35): 18587–18589. PMID 2848800 (https://www.ncbi.nlm.nih.gov/pubm ed/2848800). Archived (https://web.archive.org/web/20140417144446/http://www.jbc.org/content/263/35/18587.ab stract) from the original on 17 April 2014

15. McDowell GA, Mules EH, Fabacher P, Shapira E, Blitzer MG (1992). "The presence of two different infantile Tay– Sachs disease mutations in a Cajun population" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682822). American Journal of Human Genetics. 51 (5): 1071–1077. PMC 1682822 (https://www.ncbi.nlm.nih.gov/pmc/article s/PMC1682822). PMID 1307230 (https://www.ncbi.nlm.nih.gov/pubmed/1307230).

16. Keats BJ, Elston RC, Andermann E (1987). "Pedigree discriminant analysis of two French Canadian Tay–Sachs families". Genetic Epidemiology. 4 (2): 77–85. doi:10.1002/gepi.1370040203 (https://doi.org/10.1002%2Fgepi.1370 040203). PMID 2953646 (https://www.ncbi.nlm.nih.gov/pubmed/2953646).

17. De Braekeleer M, Hechtman P, Andermann E, Kaplan F (April 1992). "The French Canadian Tay–Sachs disease deletion mutation: Identification of probable founders". Human Genetics. 89 (1): 83–87. doi:10.1007/BF00207048 (https://doi.org/10.1007%2FBF00207048). PMID 1577470 (https://www.ncbi.nlm.nih.gov/pubmed/1577470).

18. Ohno K, Suzuki K (5 December 1988). "Multiple Abnormal beta-Hexosaminidase Alpha-Chain mRNAs in a Compound-Heterozygous Ashkenazi Jewish Patient with Tay–Sachs Disease" (http://www.jbc.org/cgi/reprint/263/3 4/18563.pdf) (PDF). Journal of Biological Chemistry. 263 (34): 18563–7. PMID 2973464 (https://www.ncbi.nlm.nih. gov/pubmed/2973464). Archived (https://web.archive.org/web/20070926115940/http://www.jbc.org/cgi/reprint/263/3 4/18563.pdf) (PDF) from the original on 26 September 2007. Retrieved 11 May 2007.

19. Kaback MM, Desnick RJ (2011). "Hexosaminidase A Deficiency" (https://www.ncbi.nlm.nih.gov/books/NBK1218/). In Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT, Smith RJ, Stephens K (eds.). GeneReviews [Internet]. Seattle, Washington, USA: University of Washington, Seattle. PMID 20301397 (https://www.ncbi.nlm.nih. gov/pubmed/20301397). Archived (https://web.archive.org/web/20140116030612/http://www.ncbi.nlm.nih.gov/book s/NBK1218/) from the original on 2014-01-16.

20. Korf, Bruce R (2000). Human genetics: A problem-based approach (2 ed.). Wiley-Blackwell. pp. 11–12. ISBN 978-0-632-04425-2.

21. Mahuran DJ (1999). "Biochemical consequences of mutations causing the GM2 gangliosidoses". Biochimica et Biophysica Acta. 1455 (2–3): 105–138. doi:10.1016/S0925-4439(99)00074-5 (https://doi.org/10.1016%2FS0925-4 439%2899%2900074-5). PMID 10571007 (https://www.ncbi.nlm.nih.gov/pubmed/10571007).

22. Hechtman P, Kaplan F (1993). "Tay–Sachs disease screening and diagnosis: Evolving technologies". DNA and Cell Biology. 12 (8): 651–665. doi:10.1089/dna.1993.12.651 (https://doi.org/10.1089%2Fdna.1993.12.651). PMID 8397824 (https://www.ncbi.nlm.nih.gov/pubmed/8397824).

23. Tittarelli R, Giagheddu M, Spadetta V (July 1966). "Typical ophthalmoscopic picture of "cherry-red spot" in an adult with the myoclonic syndrome" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC506244). The British Journal of Ophthalmology. 50 (7): 414–420. doi:10.1136/bjo.50.7.414 (https://doi.org/10.1136%2Fbjo.50.7.414). PMC 506244 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC506244). PMID 5947589 (https://www.ncbi.nlm.nih.gov/pubmed/59 47589).

24. Aragão RE, Ramos RM, Pereira FB, Bezerra AF, Fernandes DN (Jul–Aug 2009). " 'Cherry red spot' in a patient with Tay–Sachs disease: case report". Arq Bras Oftalmol. 72 (4): 537–9. doi:10.1590/S0004-27492009000400019 (https://doi.org/10.1590%2FS0004-27492009000400019). PMID 19820796 (https://www.ncbi.nlm.nih.gov/pubmed/ 19820796).

25. Seshadri R, Christopher R, Arvinda HR (2011). "Teaching NeuroImages: MRI in infantile Sandhoff disease". Neurology. 77 (5): e34. doi:10.1212/WNL.0b013e318227b215 (https://doi.org/10.1212%2FWNL.0b013e318227b2 15). PMID 21810694 (https://www.ncbi.nlm.nih.gov/pubmed/21810694).

26. Stoller D (1997). "Prenatal Genetic Screening: The Enigma of Selective Abortion". Journal of Law and Health. 12 (1): 121–140. PMID 10182027 (https://www.ncbi.nlm.nih.gov/pubmed/10182027).

27. "Chorionic Villus Sampling and Amniocentesis: Recommendations for Prenatal Counseling" (https://www.cdc.gov/ mmwr/preview/mmwrhtml/00038393.htm). United States, Center for Disease Control. Archived (https://web.archiv e.org/web/20090714185556/http://www.cdc.gov/mmwr/preview/mmwrhtml/00038393.htm) from the original on 14 July 2009. Retrieved 18 June 2009

28. Bodurtha J, Strauss JF (2012). "Genomics and perinatal care" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC487 7696). N. Engl. J. Med. 366 (1): 64–73. doi:10.1056/NEJMra1105043 (https://doi.org/10.1056%2FNEJMra110504 3). PMC 4877696 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877696). PMID 22216843 (https://www.ncbi.nl m.nih.gov/pubmed/22216843).

29. Marik, J J (13 April 2005). "Preimplantation Genetic Diagnosis" (http://emedicine.medscape.com/article/273415-ov erview). eMedicine.com. Archived (https://web.archive.org/web/20090131094639/http://emedicine.medscape.com/ article/273415-overview) from the original on 31 January 2009. Retrieved 10 May 2007.

30. Ekstein, J; Katzenstein, H (2001). "The Dor Yeshorim story: Community-based carrier screening for Tay–Sachs disease". Tay–Sachs Disease. Advances in Genetics. 44. pp. 297–310. doi:10.1016/S0065-2660(01)44087-9 (http s://doi.org/10.1016%2FS0065-2660%2801%2944087-9). ISBN 978-0-12-017644-1. PMID 11596991 (https://www. ncbi.nlm.nih.gov/pubmed/11596991).

31. Colaianni A, Chandrasekharan S, Cook-Deegan R (2010). "Impact of Gene Patents and Licensing Practices on Access to Genetic Testing and Carrier Screening for Tay–Sachs and Canavan Disease" (https://www.ncbi.nlm.nih.g ov/pmc/articles/PMC3042321). Genetics in Medicine. 12 (4 Suppl): S5–S14. doi:10.1097/GIM.0b013e3181d5a669 (https://doi.org/10.1097%2FGIM.0b013e3181d5a669). PMC 3042321 (https://www.ncbi.nlm.nih.gov/pmc/articles/P MC3042321). PMID 20393311 (https://www.ncbi.nlm.nih.gov/pubmed/20393311).

32. Eeg-Olofsson L, Kristensson K, Sourander P, Svennerholm L (1966). "Tay–Sachs disease. A generalized metabolic disorder". Acta Paediatrica Scandinavica. 55 (6): 546–62. doi:10.1111/j.1651-2227.1966.tb15254.x (http s://doi.org/10.1111%2Fj.1651-2227.1966.tb15254.x). PMID 5972561 (https://www.ncbi.nlm.nih.gov/pubmed/59725 61).

33. Shapiro BE, Hatters-Friedman S, Fernandes-Filho JA, Anthony K, Natowicz MR (12 September 2006). "Late-onset Tay–Sachs disease: Adverse effects of medications and implications for treatment". Neurology. 67 (5): 875–877. doi:10.1212/01.wnl.0000233847.72349.b6 (https://doi.org/10.1212%2F01.wnl.0000233847.72349.b6). PMID 16966555 (https://www.ncbi.nlm.nih.gov/pubmed/16966555).

34. Rozenberg R, Pereira Lda V (2001). "The frequency of Tay–Sachs disease causing mutations in the Brazilian Jewish population justifies a carrier screening program". Sao Paulo medical journal [Revista paulista de medicina]. 119 (4): 146–149. doi:10.1590/s1516-31802001000400007 (https://doi.org/10.1590%2Fs1516-3180200100040000 7). PMID 11500789 (https://www.ncbi.nlm.nih.gov/pubmed/11500789).

35. GM2 Gangliosidoses – Introduction And Epidemiology (http://emedicine.medscape.com/article/951943-overview) Archived (https://web.archive.org/web/20120420200011/http://emedicine.medscape.com/article/951943-overview) 2012-04-20 at the Wayback Machine at Medscape. Author: David H Tegay. Updated: Mar 9, 2012

36. Chakravarti A, Chakraborty R (1978). "Elevated frequency of Tay–Sachs disease among Ashkenazic Jews unlikely by genetic drift alone" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1685578). American Journal of Human Genetics. 30 (3): 256–261. PMC 1685578 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1685578). PMID 677122 (https://www.ncbi.nlm.nih.gov/pubmed/677122).

37. Frisch A, Colombo R, Michaelovsky E, Karpati M, Goldman B, Peleg L (March 2004). "Origin and spread of the 1278insTATC mutation causing Tay–Sachs disease in Ashkenazi Jews: Genetic drift as a robust and parsimonious hypothesis". Human Genetics. 114 (4): 366–376. doi:10.1007/s00439-003-1072-8 (https://doi.org/10.1007%2Fs004 39-003-1072-8). PMID 14727180 (https://www.ncbi.nlm.nih.gov/pubmed/14727180).

38. Koeslag JH, Schach SR (1984). "Tay–Sachs disease and the role of reproductive compensation in the maintenance of ethnic variations in the incidence of autosomal recessive disease". Annals of Human Genetics. 48 (3): 275–281. doi:10.1111/j.1469-1809.1984.tb01025.x (https://doi.org/10.1111%2Fj.1469-1809.1984.tb01025.x). PMID 6465844 (https://www.ncbi.nlm.nih.gov/pubmed/6465844).

39. Risch N, Tang H, Katzenstein H, Ekstein J (2003). "Geographic Distribution of Disease Mutations in the Ashkenazi Jewish Population Supports Genetic Drift over Selection" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180346) . American Journal of Human Genetics. 72 (4): 812–822. doi:10.1086/373882 (https://doi.org/10.1086%2F373882). PMC 1180346 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180346). PMID 12612865 (https://www.ncbi.nlm.ni h.gov/pubmed/12612865).

40. Slatkin M (2004). "A Population-Genetic Test of Founder Effects and Implications for Ashkenazi Jewish Diseases" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1216062). American Journal of Human Genetics. 75 (2): 282–293. doi:10.1086/423146 (https://doi.org/10.1086%2F423146). PMC 1216062 (https://www.ncbi.nlm.nih.gov/pmc/article s/PMC1216062). PMID 15208782 (https://www.ncbi.nlm.nih.gov/pubmed/15208782).

41. Tay, Waren (1881). "Symmetrical changes in the region of the yellow spot in each eye of an infant". Transactions of the Ophthalmological Society. 1: 55–57.

42. Sachs, Bernard (1887). "On arrested cerebral development with special reference to cortical pathology". Journal of Nervous and Mental Disease. 14 (9): 541–554. doi:10.1097/00005053-188714090-00001 (https://doi.org/10.109 7%2F00005053-188714090-00001). hdl:10192/32703 (https://hdl.handle.net/10192%2F32703).

43. Reuter, Shelley Z (Summer 2006). "The Genuine Jewish Type: Racial Ideology and Anti-Immigrationism in Early Medical Writing about Tay–Sachs Disease". The Canadian Journal of Sociology. 31 (3): 291–323. doi:10.1353/cjs.2006.0061 (https://doi.org/10.1353%2Fcjs.2006.0061).

44. "Amaurotic Idiocy" (http://www.jewishencyclopedia.com/articles/8057-idiocy#anchor1). The Jewish Encyclopedia. New York: Funk and Wagnalls. 1901–1906. Archived (https://web.archive.org/web/20120303094221/http://www.jew ishencyclopedia.com/articles/8057-idiocy#anchor1) from the original on 3 March 2012. Retrieved 7 March 2009.

45. Okada S, O'Brien JS (1969). "Tay–Sachs disease: Generalized absence of a beta-D-N-acetylhexosaminidase component". Science. 165 (3894): 698–700. Bibcode:1969Sci...165..698O (https://ui.adsabs.harvard.edu/abs/1969 Sci...165..698O). doi:10.1126/science.165.3894.698 (https://doi.org/10.1126%2Fscience.165.3894.698). PMID 5793973 (https://www.ncbi.nlm.nih.gov/pubmed/5793973).

46. O'Brien JS, Okada S, Chen A, Fillerup DL (1970). "Tay–Sachs disease: Detection of heterozygotes and homozygotes by serum hexaminidase assay". New England Journal of Medicine. 283 (1): 15–20. doi:10.1056/NEJM197007022830104 (https://doi.org/10.1056%2FNEJM197007022830104). PMID 4986776 (http s://www.ncbi.nlm.nih.gov/pubmed/4986776).

47. O'Brien, John S (1983). "The Gangliosidoses". In Stanbury, J B; et al. (eds.). The Metabolic Basis of Inherited Disease. New York: McGraw Hill. pp. 945–969.

48. Sagi M (1998). "Ethical aspects of genetic screening in Israel". Science in Context. 11 (3–4): 419–429. doi:10.1017/s0269889700003112 (https://doi.org/10.1017%2Fs0269889700003112). PMID 15168671 (https://ww w.ncbi.nlm.nih.gov/pubmed/15168671).

49. Kimura, Motoo (1983). The Neutral Theory of Molecular Evolution. Cambridge: Cambridge University Press. ISBN 978-0-521-23109-1.

50. Matsuoka K, Tamura T, Tsuji D, Dohzono Y, Kitakaze K, Ohno K, Saito S, Sakuraba H, Itoh K (14 October 2011). "Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis" (http://www.nature.com/mt/journal/v19/n6/full/mt201127a.html). Molecular Therapy. 19 (6): 1017–1024. doi:10.1038/mt.2011.27 (https://doi.org/10.1038%2Fmt.2011.27). PMC 3129794 (https://www.ncbi.nlm. nih.gov/pmc/articles/PMC3129794). PMID 21487393 (https://www.ncbi.nlm.nih.gov/pubmed/21487393). Archived (https://web.archive.org/web/20140821122104/http://www.nature.com/mt/journal/v19/n6/full/mt201127a.html) from the original on 21 August 2014.

51. Torres PA, Zeng BJ, Porter BF, Alroy J, Horak F, Horak J, Kolodny EH (2010). "Tay–Sachs disease in Jacob sheep". Molecular Genetics and Metabolism. 101 (4): 357–363. doi:10.1016/j.ymgme.2010.08.006 (https://doi.org/ 10.1016%2Fj.ymgme.2010.08.006). ISSN 1096-7192 (https://www.worldcat.org/issn/1096-7192). PMID 20817517 (https://www.ncbi.nlm.nih.gov/pubmed/20817517).

52. Porter BF, Lewis BC, Edwards JF, Alroy J, Zeng BJ, Torres PA, Bretzlaff KN, Kolodny EH (2011). "Pathology of GM2 Gangliosidosis in Jacob Sheep". Veterinary Pathology. 48 (3): 807–813. doi:10.1177/0300985810388522 (htt ps://doi.org/10.1177%2F0300985810388522). ISSN 0300-9858 (https://www.worldcat.org/issn/0300-9858). PMID 21123862 (https://www.ncbi.nlm.nih.gov/pubmed/21123862).

53. Kolodny E, Horak F, Horak J (2011). "Jacob sheep breeders find more Tay–Sachs carriers" (http://www.albc-usa.or g/Newsletter/newsletterJanFeb2011.html). ALBC Newsletter. Archived (https://web.archive.org/web/201203200746 43/http://www.albc-usa.org/Newsletter/newsletterJanFeb2011.html) from the original on 20 March 2012. Retrieved 5 May 2011.

54. Platt FM, Neises GR, Reinkensmeier G, Townsend MJ, Perry VH, Proia RL, Winchester B, Dwek RA, Butters TD (1997). "Prevention of lysosomal storage in Tay–Sachs mice treated with N-butyldeoxynojirimycin". Science. 276 (5311): 428–431. doi:10.1126/science.276.5311.428 (https://doi.org/10.1126%2Fscience.276.5311.428). PMID 9103204 (https://www.ncbi.nlm.nih.gov/pubmed/9103204).

55. Lachmann RH, Platt FM (2001). "Substrate reduction therapy for glycosphingolipid storage disorders". Expert Opinion on Investigational Drugs. 10 (3): 455–466. doi:10.1517/13543784.10.3.455 (https://doi.org/10.1517%2F13 543784.10.3.455). PMID 11227045 (https://www.ncbi.nlm.nih.gov/pubmed/11227045).

56. Igdoura SA, Mertineit C, Trasler JM, Gravel RA (1999). "Sialidase-mediated depletion of GM2 ganglioside in Tay– Sachs neuroglia cells". Human Molecular Genetics. 8 (6): 1111–1116. doi:10.1093/hmg/8.6.1111 (https://doi.org/10. 1093%2Fhmg%2F8.6.1111). PMID 10332044 (https://www.ncbi.nlm.nih.gov/pubmed/10332044).

57. "Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses" (https://www.clinicaltrials.gov/ct2/show/NCT00672022?term=tay-sachs&ran k=3). 5 May 2008. Archived (https://web.archive.org/web/20120213083854/http://www.clinicaltrials.gov/ct2/show/N CT00672022?term=tay-sachs&rank=3) from the original on 13 February 2012. Retrieved 10 April 2012.

58. Kolodny EH, Neudorfer O, Gianutsos J, Zaroff C, Barnett N, Zeng BJ, Raghavan S, Torres P, Pastores GM (2004). "Late-onset Tay–Sachs disease: Natural history and treatment with OGT 918 (Zavesca™)". Journal of Neurochemistry. 90 (S1): 54–55. Bibcode:2006JNeur..26.9606G (https://ui.adsabs.harvard.edu/abs/2006JNeur..2 6.9606G). doi:10.1111/j.1471-4159.2004.02650_.x (https://doi.org/10.1111%2Fj.1471-4159.2004.02650_.x). ISSN 0022-3042 (https://www.worldcat.org/issn/0022-3042).

59. Osher E, Fattal-Valevski A, Sagie L, Urshanski N, Amir-Levi Y, Katzburg S, Peleg L, Lerman-Sagie T, Zimran A, Elstein D, Navon R, Stern N, Valevski A (March 2011). "Pyrimethamine increases β-hexosaminidase A activity in patients with Late Onset Tay Sachs". Mol. Genet. Metab. 102 (3): 356–63. doi:10.1016/j.ymgme.2010.11.163 (http s://doi.org/10.1016%2Fj.ymgme.2010.11.163). PMID 21185210 (https://www.ncbi.nlm.nih.gov/pubmed/21185210).

60. Prasad, Vinod K.; Mendizabal, Adam; Parikh, Suhag H.; Szabolcs, Paul; Driscoll, Timothy A.; Page, Kristin; Lakshminarayanan, Sonali; Allison, June; Wood, Susan (2008-10-01). "Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556628). Blood. 112 (7): 2979–2989. doi:10.1182/blood-2008-03-140830 (https://doi.org/10.1182%2Fblood-2008-03-14083 0). ISSN 0006-4971 (https://www.worldcat.org/issn/0006-4971). PMC 2556628 (https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2556628). PMID 18587012 (https://www.ncbi.nlm.nih.gov/pubmed/18587012).

61. William Hathaway (May 16, 2006). "Umbilical Cord Blood Is Child's Last Hope, Stem Cells Could Halt Tay–Sachs Damage" (http://articles.courant.com/2006-05-16/features/0605160129_1_umbilical-cord-blood-genetic-disorder-di sease). Hartford Courant.