Tay–Sachs disease

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first reported were between Russian and Polish Jews; but recently there have been reported cases occurring in non-Jewish children. The chief characteristics of the disease are progressive mental and physical enfeeblement; weakness and paralysis of all the extremities; and marasmus, associated with symmetrical changes in the macula lutea. On investigation of the reported cases, they found that neither consanguinity nor syphilitic, alcoholic, or nervous antecedents in the family history are factors in the etiology of the disease. No preventive measures have as yet been discovered, and no treatment has been of benefit, all the cases having terminated fatally.

972: 520: 720:(i.e. will develop full-blown disease). A normal:mutated heterozygote (heterozygous individual, also known as a 'carrier') has at least half of the normal enzyme activity level, due to the expression of the wild-type allele. This level is normally enough to enable normal functioning and thus prevent phenotypic expression (i.e. a normal:mutated carrier will not become ill). 819:. Total hexosaminidase enzyme activity is decreased in individuals with Tay–Sachs as is the percentage of hexosaminidase A. After confirmation of decreased enzyme activity in an individual, confirmation by molecular analysis can be pursued. All patients with infantile onset Tay–Sachs disease have a "cherry red" 1109:

It is a curious fact that amaurotic family idiocy, a rare and fatal disease of children, occurs mostly among Jews. The largest number of cases has been observed in the United States—over thirty in number. It was at first thought that this was an exclusively Jewish disease because most of the cases at

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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

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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

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In 1969, Shintaro Okada and John S. O'Brien showed that Tay–Sachs disease was caused by an enzyme defect; they also proved that Tay–Sachs patients could be diagnosed by an assay of hexosaminidase A activity. The further development of enzyme assays demonstrated that levels of hexosaminidases A

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As Tay–Sachs disease is a deficiency of β-hexosaminidase A, deterioration of affected individuals could be slowed or stopped through the use of a substance that increases its activity. However, since in infantile Tay–Sachs disease there is no β-hexosaminidase A, the treatment would be ineffective,

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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

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Both Tay and Sachs reported their first cases among Ashkenazi Jewish families. Tay reported his observations in 1881 in the first volume of the proceedings of the British Ophthalmological Society, of which he was a founding member. By 1884, he had seen three cases in a single family. Years later,

643:. Two mutations, unrelated to the Ashkenazi/Cajun mutation, are absent in France but common among certain French-Canadian communities living in southeastern Quebec and Acadians from the Province of New Brunswick. Pedigree analysis suggests the mutations were uncommon before the late 17th century. 1100:

had published his article on the genetics of peas in 1865, Mendel's paper was largely forgotten for more than a generation – not rediscovered by other scientists until 1899. Thus, the Mendelian model for explaining Tay–Sachs was unavailable to scientists and doctors of the time. The first

637:. 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. 474:

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

1125:(hostility to immigrants) in the United States. Opponents of immigration often questioned whether immigrants from southern and eastern Europe could be assimilated into American society. Reports of Tay–Sachs disease contributed to a perception among nativists that Jews were an inferior race. 1129:

and B could be measured in patients and carriers, allowing the reliable detection of heterozygotes. During the early 1970s, researchers developed protocols for newborn testing, carrier screening, and pre-natal diagnosis. By the end of 1979, researchers had identified three variant forms of

40: 906:, 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 532: 506:

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

847:. Thus, this cherry-red spot is the only normal part of the retina; it shows up in contrast to the rest of the retina. Microscopic analysis of the retinal neurons shows they are distended from excess ganglioside storage. Unlike other lysosomal storage diseases (e.g., 257:, with death usually occurring by the age of three to five. Less commonly, the disease may occur later in childhood, adolescence, or adulthood (juvenile or late-onset). These forms tend to be less severe, but the juvenile form typically results in death by age 15. 659:

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

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As of 2010, even with the best care, children with infantile Tay–Sachs disease usually die by the age of 4. Children with the juvenile form are likely to die between the ages 5–15, while the lifespans of those with the adult form will probably not be affected.

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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".

551:, 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. If a child received a normal copy from one parent and a mutated copy from the other, it is a 1306:. 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 1354:, 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 1147:

Since carrier testing for Tay–Sachs began in 1971, millions of Ashkenazi Jews have been screened as carriers. Jewish communities embraced the cause of genetic screening from the 1970s on. The success with Tay–Sachs disease has led

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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".

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Flotte, Terence R.; Cataltepe, Oguz; Puri, Ajit; Batista, Ana Rita; Moser, Richard; McKenna-Yasek, Diane; Douthwright, Catherine; Gernoux, Gwladys; Blackwood, Meghan; Mueller, Christian; Tai, Phillip W. L. (10 February 2022).

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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.

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establish a new population. In this illustration, the original population is on the left with three possible founder populations on the right. Two of the three founder populations are genetically distinct from the original

1042:. Parents who lose a child because of disease tend to "compensate" by having additional children following the loss. This phenomenon may maintain and possibly even increase the incidence of autosomal recessive disease. 692:

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.

4637: 4622: 4050:"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" 664:

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

245:. The most common form is infantile Tay–Sachs disease, which becomes apparent around the age of three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by 3824:

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".

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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

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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™)".

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to ease the symptoms and extend life by reducing the chance of contracting infections. Infants are given feeding tubes when they can no longer swallow. In late-onset Tay–Sachs, medication (e.g.,

744:. When hexosaminidase A is no longer functioning properly, the lipids accumulate in the brain and interfere with normal biological processes. Hexosaminidase A specifically breaks down 696:

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

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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

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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".

1193:. In applied genetics (selective and agricultural breeding), this controversy has reflected the century-long debate over whether dominance or overdominance provides the best explanation for 787:) occurs because a mutation inherited from both parents deactivates or inhibits this process. Most Tay–Sachs mutations probably do not directly affect protein functional elements (e.g., the 1824:

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".

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gene on brain cells which causes the disease. Only two children were part of a compassionate trial presenting improvements over the natural course of the disease and no vector-related

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Tay–Sachs disease was one of the first genetic disorders for which epidemiology was studied using molecular data. Studies of Tay–Sachs mutations using new molecular techniques such as

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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".

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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 experience

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Lyn, Nicole; Pulikottil-Jacob, Ruth; Rochmann, Camille; Krupnick, Robert; Gwaltney, Chad; Stephens, Nick; Kissell, Julie; Cox, Gerald F.; Fischer, Tanya; Hamed, Alaa (2020-04-15).

1048:. This hypothesis states that the high incidence of the 1278insTATC chromosomes is the result of an elevated allele frequency that existed by chance in an early founder population. 748:

derivatives called gangliosides; these are made and biodegraded rapidly in early life as the brain develops. Patients with and carriers of Tay–Sachs can be identified by a simple

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Prasad, Vinod K.; Mendizabal, Adam; Parikh, Suhag H.; Szabolcs, Paul; Driscoll, Timothy A.; Page, Kristin; Lakshminarayanan, Sonali; Allison, June; Wood, Susan (2008-10-01).

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Bernard Sachs, an American neurologist, reported similar findings when he reported a case of "arrested cerebral development" to other New York Neurological Society members.

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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".

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De Braekeleer M, Hechtman P, Andermann E, Kaplan F (April 1992). "The French Canadian Tay–Sachs disease deletion mutation: Identification of probable founders".

1725: 1142: 884:. If both parents are identified as carriers, prenatal genetic testing can determine whether the fetus has inherited a defective gene copy from both parents. 3944: 1334:

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

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gene, one from each parent. Classic infantile Tay–Sachs disease results when a child has inherited mutations from both parents that completely stop the

3941:"Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses" 3373:

Reuter, Shelley Z (Summer 2006). "The Genuine Jewish Type: Racial Ideology and Anti-Immigrationism in Early Medical Writing about Tay–Sachs Disease".

1914:(July 1981). "Chronic GM2 gangliosidosis masquerading as atypical Friedreich's ataxia: Clinical, morphologic, and biochemical studies of nine cases". 1404:. 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. 4303: 684:. Late onset forms occur due to the diverse mutation base – people with Tay–Sachs disease may technically be heterozygotes, with two differing 312:

in nature. This may involve multiple specialities as well as psychosocial support for the family. The disease is rare in the general population. In

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Critics point to the procedure's harsh nature—and the fact that it is unapproved. Other significant issues involve the difficulty in crossing the

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Porter BF, Lewis BC, Edwards JF, Alroy J, Zeng BJ, Torres PA, Bretzlaff KN, Kolodny EH (2011). "Pathology of GM2 Gangliosidosis in Jacob Sheep".

1036:. When applied to a particular allele, this theory posits that mutation carriers have a selective advantage, perhaps in a particular environment. 3024: 3489:

O'Brien JS, Okada S, Chen A, Fillerup DL (1970). "Tay–Sachs disease: Detection of heterozygotes and homozygotes by serum hexaminidase assay".

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Three general classes of theories have been proposed to explain the high frequency of Tay–Sachs carriers in the Ashkenazi Jewish population:

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gene. This mutation is the most prevalent mutation in the Ashkenazi Jewish population, and leads to the infantile form of Tay–Sachs disease.

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efficiently even when it is directly by them. Therefore, this approach to treatment of Tay–Sachs disease has also been ineffective so far.

4281: 3802: 4780: 2352:"Multiple Abnormal beta-Hexosaminidase Alpha-Chain mRNAs in a Compound-Heterozygous Ashkenazi Jewish Patient with Tay–Sachs Disease" 1698: 1631: 4440: 3905:

Igdoura SA, Mertineit C, Trasler JM, Gravel RA (1999). "Sialidase-mediated depletion of GM2 ganglioside in Tay–Sachs neuroglia cells".

1588: 1542: 4259: 1721: 4795: 2850:"Impact of Gene Patents and Licensing Practices on Access to Genetic Testing and Carrier Screening for Tay–Sachs and Canavan Disease" 2058: 1387:

but for people affected by Late-Onset Tay–Sachs disease, β-hexosaminidase A is present, so the treatment may be effective. The drug

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carries out an anonymous screening program so that carriers for Tay–Sachs and other genetic disorders can avoid marrying each other.

4548: 3582: 3052: 2779: 2703: 2026: 2009: 1114: 2143:"The major defect in Ashkenazi Jews with Tay–Sachs disease is an insertion in the gene for the alpha-chain of beta-hexosaminidase" 1489: 1564: 4755: 4276: 2985:"The frequency of Tay–Sachs disease causing mutations in the Brazilian Jewish population justifies a carrier screening program" 2172: 1279:

enzyme itself has been thought to be too large to pass through the specialized cell layer in the blood vessels that forms the

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As of 2010 there was no treatment that addressed the cause of Tay–Sachs disease or could slow its progression; people receive

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This is a highly invasive procedure which involves destroying the patient's blood system with chemotherapy and administering

4775: 3635:"Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis" 1957:

Kaback MM (December 2000). "Population-based genetic screening for reproductive counseling: the Tay–Sachs disease model".

1133:, including Sandhoff disease and the AB variant of GM2-gangliosidosis, accounting for false negatives in carrier testing. 831:. This red spot is a retinal area that appears red because of gangliosides in the surrounding retinal ganglion cells. The 600:(i.e., the enzyme), sometimes severely inhibiting its function. In recent years, population studies and pedigree analysis 491:

and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness, particularly a

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Eeg-Olofsson L, Kristensson K, Sourander P, Svennerholm L (1966). "Tay–Sachs disease. A generalized metabolic disorder".

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is about 1 in 300. The incidence is approximately 1 in 320,000 newborns in the general population in the United States.

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and progressive neurological deterioration. Symptoms of late-onset Tay–Sachs – which typically begin to be seen in

3212:"Geographic Distribution of Disease Mutations in the Ashkenazi Jewish Population Supports Genetic Drift over Selection" 2804:

Ekstein, J; Katzenstein, H (2001). "The Dor Yeshorim story: Community-based carrier screening for Tay–Sachs disease".

1853:"Patient and caregiver perspectives on burden of disease manifestations in late-onset Tay-Sachs and Sandhoff diseases" 4579: 4270: 3689: 2227:

Keats BJ, Elston RC, Andermann E (1987). "Pedigree discriminant analysis of two French Canadian Tay–Sachs families".

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In patients with a clinical suspicion for Tay–Sachs disease, with any age of onset, the initial testing involves an

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of GM2-ganglioside requires three proteins. Two of them are subunits of hexosaminidase A; the third is a small

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Okada S, O'Brien JS (1969). "Tay–Sachs disease: Generalized absence of a beta-D-N-acetylhexosaminidase component".

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testing methods), it was intensely studied as a model for all such diseases, and researchers sought evidence of a

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Torres PA, Zeng BJ, Porter BF, Alroy J, Horak F, Horak J, Kolodny EH (2010). "Tay–Sachs disease in Jacob sheep".

1411:, as well as the great expense, as each unit of cord blood costs $ 25,000, and adult recipients need many units. 3940: 1156:

for all couples and opened discussions about the proper scope of genetic testing for other disorders in Israel.

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within cells, leading to toxicity. Diagnosis may be supported by measuring the blood hexosaminidase A level or

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Matsuoka K, Tamura T, Tsuji D, Dohzono Y, Kitakaze K, Ohno K, Saito S, Sakuraba H, Itoh K (14 October 2011).

1338:. The Tay–Sachs model provided by the Jacob sheep is the first to offer promise as a means for gene therapy 1159:

Because Tay–Sachs disease was one of the first autosomal recessive genetic disorders for which there was an

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Chong, Jessica X.; Ouwenga, Rebecca; Anderson, Rebecca L.; Waggoner, Darrel J.; Ober, Carole (2012-10-05).

1759: 1290:(CSF) which bathes the brain. However, intracerebral neurons seem unable to take up this physically large 938:

for depression) can sometimes control psychiatric symptoms and seizures, although some medications (e.g.,

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Sachs, who recognized that the disease had a familial basis, proposed that the disease should be called

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manner. The mutation disrupts the activity of the enzyme, which results in the build-up of the molecule

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for the enzyme. Deficiency in any one of these proteins leads to ganglioside storage, primarily in the

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as a determinant of evolution and of variation within a population, while neutralists favor a form of

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Lachmann RH, Platt FM (2001). "Substrate reduction therapy for glycosphingolipid storage disorders".

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Researchers have also tried directly instilling the deficient enzyme hexosaminidase A into the

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analysis have brought an emerging consensus among researchers supporting the founder effect theory.

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mutations that both inactivate, alter, or inhibit enzyme activity. When a patient has at least one

1105:, published in 12 volumes between 1901 and 1906, described what was then known about the disease: 1022:

have a 1 in 50 chance of being a carrier. In the general population, the incidence of carriers as

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Hechtman P, Kaplan F (1993). "Tay–Sachs disease screening and diagnosis: Evolving technologies".

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changes and noted an increased rate of disease in Ashkenazi Jews. Carriers of a single Tay–Sachs

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that operates to eliminate deleterious alleles. The balancing hypothesis, often associated with

4765: 4593: 4324: 3794: 3741: 3074:"Elevated frequency of Tay–Sachs disease among Ashkenazic Jews unlikely by genetic drift alone" 1420: 1183:

population suggests a past selective advantage for heterozygous carriers of these conditions."

1082: 1057: 1053: 1033: 903: 888:(CVS), the most common form of prenatal diagnosis, can be performed between 10 and 14 weeks of 656: 508: 363:

are typically normal. It has been hypothesized that being a carrier may confer protection from

340:, the condition is more common. Approximately 1 in 3,600 Ashkenazi Jews at birth are affected. 157: 4706: 2543:"Typical ophthalmoscopic picture of "cherry-red spot" in an adult with the myoclonic syndrome" 2416:. In Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT, Smith RJ, Stephens K (eds.). 2057:

Jarvis, Sarah; Henderson, Roger; Stone, Joanne; Eddleman, Keith; Duenwald, Mary (2011-09-23).

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is usually performed at 15–18 weeks. These procedures have risks of miscarriage of 1% or less.

367:, explaining the persistence of the allele in certain populations. Researchers are looking at 4406: 3261:"A Population-Genetic Test of Founder Effects and Implications for Ashkenazi Jewish Diseases" 1243: 1231: 1221: 1217: 1205: 1186:

This controversy among researchers has reflected various debates among geneticists at large:

840: 597: 570: 411: 1534: 1220:, states that heterozygosity will be common at loci, and that it frequently reflects either 4455: 3447: 2471:

Mahuran DJ (1999). "Biochemical consequences of mutations causing the GM2 gangliosidoses".

2188:"The presence of two different infantile Tay–Sachs disease mutations in a Cajun population" 1729: 935: 589: 1117:

peaked in the period 1880–1924, with the immigrants arriving from Russia and countries in

8: 4641: 3333:(1887). "On arrested cerebral development with special reference to cortical pathology". 3311:(1881). "Symmetrical changes in the region of the yellow spot in each eye of an infant". 2699: 2313:

Fraikor, Arlene L. (1977). "Tay-Sachs disease: genetic drift among the Ashkenazim Jews".

1335: 1287: 1225: 1213: 1168: 1122: 1102: 979: 544: 524: 286: 132: 4170: 4137: 3451: 3049: 2775: 539:

gene is located on the long (q) arm of human chromosome 15, between positions 23 and 24.

4500: 4372: 4367: 4183: 4082: 4049: 3991: 3887: 3775: 3659: 3634: 3564: 3471: 3390: 3285: 3260: 3236: 3211: 3189: 3177: 3146: 3090: 3073: 2965: 2953: 2922: 2910: 2874: 2849: 2751: 2726: 2295: 2252: 2204: 2187: 2118: 2085: 2039: 1990: 1939: 1887: 1852: 1806: 1212:, and that most individuals are homozygous for that wild type, while most selection is 1153: 1130: 911: 881: 860: 298: 75: 4646: 3979: 2813: 2700:"Chorionic Villus Sampling and Amniocentesis: Recommendations for Prenatal Counseling" 2567: 2542: 2484: 2371: 2159: 1650: 1481: 877:

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

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GeneReviews/NCBI/NIH/UW entry on hexosaminidase A deficiency, Tay–Sachs disease

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O'Brien, John S (1983). "The Gangliosidoses". In Stanbury, J B; et al. (eds.).

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criteria to distinguish it from other neurological disorders with similar symptoms.

4717: 4451: 4376: 4333: 4165: 4149: 4107:"Umbilical Cord Blood Is Child's Last Hope, Stem Cells Could Halt Tay–Sachs Damage" 4077: 4061: 4022: 3975: 3914: 3891: 3871: 3836: 3779: 3751: 3698: 3654: 3646: 3548: 3498: 3475: 3455: 3382: 3350: 3342: 3280: 3272: 3231: 3223: 3173: 3130: 3085: 2996: 2949: 2906: 2869: 2861: 2809: 2746: 2738: 2644: 2603: 2562: 2554: 2515: 2480: 2366: 2324: 2279: 2236: 2199: 2154: 2142: 2113: 2097: 2021: 1994: 1966: 1923: 1882: 1864: 1790: 1367: 1180: 856: 784: 729: 655:

directly for genetic diseases. Researchers of that era did not yet know how common

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Stoller D (1997). "Prenatal Genetic Screening: The Enigma of Selective Abortion".

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toxicity – then this new form of therapy could essentially cure the disease.

58:'s center appears bright red because it is surrounded by a whiter than usual area. 4671: 4065: 3840: 3459: 3056: 2865: 2649: 2632: 2010:"Tay–Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene" 1339: 1007: 931: 907: 848: 836: 792: 402:

with Tay–Sachs disease appear to develop normally for the first six months after

325: 317: 309: 294: 290: 275: 180: 150: 55: 47: 4728: 4026: 3702: 3502: 552: 4682: 4587: 4558: 4526: 4504: 4476: 4354: 4153: 2315: 2101: 1869: 1118: 1045: 1019: 987: 975: 828: 677: 652: 612: 605: 574: 356: 313: 279: 166: 4631: 4254: 3875: 3552: 3134: 2413: 584:. By 2000, more than 100 different mutations had been identified in the human 4744: 4429: 4421: 4410: 4227:"Parents spark breakthrough gene therapy for children with Tay-Sachs disease" 4203:"First gene therapy for Tay-Sachs disease successfully given to two children" 4161: 4073: 3987: 3763: 3755: 3710: 3330: 2939: 2443: 2109: 1978: 1878: 1428: 1388: 1303: 1247: 1234:. In theoretical population genetics, selectionists emphasize the primacy of 1175:(carriers) have or had a selective advantage. The presence of four different 1172: 1097: 1078: 999: 995: 943: 893: 844: 808: 741: 624: 492: 352: 271: 219: 2519: 2240: 4471: 4179: 4091: 4034: 3926: 3918: 3883: 3771: 3718: 3668: 3560: 3294: 3245: 3142: 3010: 2961: 2896: 2883: 2831: 2760: 2685: 2658: 2617: 2492: 2425: 2127: 1986: 1896: 1419:

On 10 February 2022, the first ever gene therapy was announced, it uses an

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were two physicians. They described the disease's progression and provided

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basis of Tay–Sachs disease was first becoming known, no mutations had been

648: 548: 385: 368: 364: 329: 250: 93: 3848: 3510: 3467: 3386: 3185: 2918: 2742: 2590:

Aragão RE, Ramos RM, Pereira FB, Bezerra AF, Fernandes DN (Jul–Aug 2009).

2576: 2527: 2380: 2291: 2248: 2213: 2168: 2035: 1935: 1837: 1802: 588:

gene. These mutations have included single base insertions and deletions,

4701: 4514: 4363: 4349: 3099: 2558: 2336: 1927: 1794: 1569: 1362:

Another metabolic therapy under investigation for Tay–Sachs disease uses

1204:. The classical hypothesis of genetic variability, often associated with 951: 947: 788: 681: 480: 447: 242: 4723: 3650: 3355: 2283: 1970: 1401: 1315: 816: 812: 760: 756: 749: 745: 500: 463: 451: 423: 403: 4614: 2027:

10.1002/(SICI)1098-1004(1997)9:3<195::AID-HUMU1>3.0.CO;2-7

596:, and other more complex patterns. Each of these mutations alters the 4712: 4486: 4466: 4398: 3308: 1363: 1355: 1209: 1194: 1074: 1015: 917:

Pre-marriage screening. In Orthodox Jewish circles, the organization

889: 772: 717: 712: 697: 616: 578: 496: 455: 443: 431: 415: 344: 337: 254: 214: 188: 2592:"'Cherry red spot' in a patient with Tay–Sachs disease: case report" 2269: 4522: 4338: 3276: 3227: 2847: 1850: 1291: 1272: 1152:

to become the first country that offers free genetic screening and

1096:. However, its genetic basis was still poorly understood. Although 1023: 737: 728:

Tay–Sachs disease is caused by insufficient activity of the enzyme

559: 466:. Death usually occurs between the ages of five and fifteen years. 128: 89: 4011: 1687:(3 ed.). Springer Science & Business Media. p. 578. 3539:

Sagi M (1998). "Ethical aspects of genetic screening in Israel".

2186:

McDowell GA, Mules EH, Fabacher P, Shapira E, Blitzer MG (1992).

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Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

608:. Initial research focused on several such founder populations: 519: 4626: 3965: 3025:"1,000 New York Irish to get tested for Tay Sachs disease gene" 2420:. Seattle, Washington, USA: University of Washington, Seattle. 1755: 1374:, which catalyzes the first step in synthesizing glucose-based 1149: 824: 820: 634: 581: 488: 459: 407: 399: 360: 348: 321: 282: 206: 51: 4047: 1823: 414:

of mental and physical abilities begins. The child may become

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Vogel and Motulsky's Human Genetics: Problems and Approaches

531: 347:, who in 1881 first described a symptomatic red spot on the 3209: 2540: 1780: 1424: 1319: 764: 620: 566: 476: 419: 266: 4134: 3632: 2630: 1342:, which may prove useful for disease treatment in humans. 795:(disrupting function) or disable intracellular transport. 2633:"Teaching NeuroImages: MRI in infantile Sandhoff disease" 2589: 1381: 863:(liver and spleen enlargement) is not seen in Tay–Sachs. 3059:

at Medscape. Author: David H Tegay. Updated: Mar 9, 2012

2808:. Advances in Genetics. Vol. 44. pp. 297–310. 1006:

is about 1 in every 3,500 newborn among Ashkenazi Jews.

700:

alleles' dominance over nonfunctional mutant alleles in

3731: 1726:

National Institute of Neurological Disorders and Stroke

1314:

of affected Jacobs sheep reveal an identical number of

978:

occur when a small number of individuals from a larger

3071: 2848:

Colaianni A, Chandrasekharan S, Cook-Deegan R (2010).

1620:. Springer Science & Business Media. p. 205. 237:

that results in the destruction of nerve cells in the

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of molecular evolution, which emphasizes the role of

547:

genetic disorder, meaning that when both parents are

410:

become distended with GM2 gangliosides, a relentless

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Other experimental methods being researched involve

33:

GM2 gangliosidosis, hexosaminidase A deficiency

3795:"Jacob sheep breeders find more Tay–Sachs carriers" 2541:Tittarelli R, Giagheddu M, Spadetta V (July 1966). 2407: 2405: 954:) are associated with significant adverse effects. 343:The disease is named after British ophthalmologist 3401: 3210:Risch N, Tang H, Katzenstein H, Ekstein J (2003). 3050:GM2 Gangliosidoses – Introduction And Epidemiology 2803: 1649: 1143:Societal and cultural aspects of Tay–Sachs disease 1018:have an occurrence similar to the Ashkenazi Jews. 3792: 3115: 3113: 3111: 3109: 2799: 2797: 2140: 604:how such mutations arise and spread within small 499:. Late-onset Tay–Sachs patients may become fully 285:known as hexosaminidase A. It is inherited in an 4742: 4104: 3437: 3368: 3366: 2402: 1910:Willner JP, Grabowski GA, Gordon RE, Bender AN, 3252: 2724: 2450:(2 ed.). Wiley-Blackwell. pp. 11–12. 1758:. United States National Institutes of Health. 1539:NORD (National Organization for Rare Disorders) 1330:. A missense mutation (G444R) was found in the 434:. Death usually occurs before the age of four. 83:: Decreased ability to turn over, sit, or crawl 3106: 2794: 2631:Seshadri R, Christopher R, Arvinda HR (2011). 2505: 1749: 1747: 1345: 763:transport protein, the GM2 activator protein ( 752:that measures hexosaminidase A activity. 4297: 3861: 3682: 3680: 3678: 3363: 3163: 3067: 3065: 2843: 2841: 2702:. United States, Center for Disease Control. 2411: 2141:Myerowitz R, Costigan FC (15 December 1988). 1680: 1259: 990:have a high incidence of Tay–Sachs and other 835:circulation is showing through "red" in this 807:to measure the activity of hexosaminidase in 384:are differentiated based on the onset age of 4200: 3313:Transactions of the Ophthalmological Society 3205: 3203: 2718: 1681:Vogel, Friedrich; Motulsky, Arno G. (2013). 1586: 1208:, maintains that most genes are of a normal 827:, easily observable by a physician using an 3523: 2890: 2007: 1744: 1529: 1527: 1423:to deliver the correct instruction for the 4304: 4290: 3725: 3675: 3528:. New York: McGraw Hill. pp. 945–969. 3415:. New York: Funk and Wagnalls. 1901–1906. 3062: 2838: 2470: 2349: 2306: 1753: 1525: 1523: 1521: 1519: 1517: 1515: 1513: 1511: 1509: 1507: 1476: 1474: 1472: 1470: 1468: 1466: 1464: 38: 4201:Sena-Esteves, Miguel (14 February 2022). 4169: 4081: 3745: 3658: 3612:. Cambridge: Cambridge University Press. 3610:The Neutral Theory of Molecular Evolution 3354: 3284: 3258: 3235: 3200: 3089: 3000: 2873: 2750: 2671: 2648: 2607: 2566: 2499: 2370: 2203: 2158: 2134: 2117: 2025: 1956: 1950: 1886: 1868: 1613: 1582: 1580: 1565:"Tay-Sachs disease - Symptoms and causes" 1462: 1460: 1458: 1456: 1454: 1452: 1450: 1448: 1446: 1444: 4260:NINDS Tay–Sachs Disease Information Page 4138:"AAV gene therapy for Tay-Sachs disease" 4007: 4005: 3786: 3526:The Metabolic Basis of Inherited Disease 2448:Human genetics: A problem-based approach 1395: 970: 530: 518: 3864:Expert Opinion on Investigational Drugs 3626: 3517: 3482: 2534: 2312: 1716: 1714: 1712: 1710: 1708: 1587:Kurreck, Jens; Stein, Cy Aaron (2016). 1504: 1115:Jewish immigration to the United States 647:In the 1960s and early 1970s, when the 623:11 (1278insTATC) results in an altered 4743: 3607: 3601: 3538: 3372: 2390:from the original on 26 September 2007 1656:. The Rosen Publishing Group. p. 1647: 1577: 1441: 1382:Increasing β-hexosaminidase A activity 1254: 1171:. A continuing controversy is whether 1136: 902:. By retrieving the mother's eggs for 767:), which acts as a substrate-specific 308:The treatment of Tay–Sachs disease is 4285: 4002: 3947:from the original on 13 February 2012 3335:Journal of Nervous and Mental Disease 3329: 3323: 3072:Chakravarti A, Chakraborty R (1978). 2773: 1817: 1756:"Online Mendelian Inheritance in Man" 1593:. John Wiley & Sons. p. 71. 1545:from the original on 20 February 2017 573:, which encodes the alpha-subunit of 523:Tay–Sachs disease is inherited in an 378: 351:of the eye; and American neurologist 193:Death often occurs in early childhood 3793:Kolodny E, Horak F, Horak J (2011). 2782:from the original on 31 January 2009 2547:The British Journal of Ophthalmology 2442: 2436: 2350:Ohno K, Suzuki K (5 December 1988). 1722:"Tay–Sachs disease Information Page" 1705: 1643: 1641: 1297: 1275:. However, in previous studies, the 1002:is a recessive carrier. The disease 3307: 3301: 2983:Rozenberg R, Pereira Lda V (2001). 2776:"Preimplantation Genetic Diagnosis" 2175:from the original on 17 April 2014. 1762:from the original on 4 January 2016 1590:Molecular Medicine: An Introduction 732:. Hexosaminidase A is a vital 13: 4781:Neurological disorders in children 4041: 3805:from the original on 20 March 2012 3265:American Journal of Human Genetics 3216:American Journal of Human Genetics 3178:10.1111/j.1469-1809.1984.tb01025.x 3078:American Journal of Human Genetics 2954:10.1212/01.wnl.0000233847.72349.b6 2911:10.1111/j.1651-2227.1966.tb15254.x 2192:American Journal of Human Genetics 2090:American Journal of Human Genetics 1728:. 14 February 2007. Archived from 1326:gene, and 86% nucleotide sequence 723: 575:beta-N-acetylhexosaminidase A 14: 4807: 4580:Cholesteryl ester storage disease 4248: 4105:William Hathaway (May 16, 2006). 3980:10.1111/j.1471-4159.2004.02650_.x 3690:Molecular Genetics and Metabolism 3419:from the original on 3 March 2012 3375:The Canadian Journal of Sociology 2706:from the original on 14 July 2009 1857:Orphanet Journal of Rare Diseases 1754:McKusick, Victor A; Hamosh, Ada. 1638: 900:Preimplantation genetic diagnosis 791:). Instead, they cause incorrect 601: 475:characterized by unsteadiness of 297:. Tay–Sachs disease is a type of 260:Tay–Sachs disease is caused by a 4796:Diseases named after discoverers 4584:Lysosomal acid lipase deficiency 3347:10.1097/00005053-188714090-00001 2432:from the original on 2014-01-16. 1701:from the original on 2017-11-05. 1634:from the original on 2017-11-05. 1492:from the original on 13 May 2017 1232:Selectionists versus neutralists 779:. Tay–Sachs disease (along with 4219: 4194: 4128: 4098: 3959: 3933: 3898: 3855: 3817: 3575: 3532: 3491:New England Journal of Medicine 3431: 3157: 3043: 3017: 3002:10.1590/s1516-31802001000400007 2976: 2933: 2767: 2725:Bodurtha J, Strauss JF (2012). 2692: 2665: 2624: 2609:10.1590/S0004-27492009000400019 2583: 2464: 2359:Journal of Biological Chemistry 2343: 2263: 2220: 2179: 2147:Journal of Biological Chemistry 2077: 2050: 2001: 1903: 1844: 1774: 1414: 966: 873:Prevention of Tay–Sachs disease 120:Infantile, juvenile, late-onset 4575:Cerebrotendinous xanthomatosis 2412:Kaback MM, Desnick RJ (2011). 1959:European Journal of Pediatrics 1826:Journal of Clinical Psychiatry 1674: 1607: 1557: 1191:Dominance versus overdominance 914:among other genetic disorders. 201:Rare in the general population 171:neuronal ceroid lipofuscinoses 1: 4756:Autosomal recessive disorders 4496:Multiple sulfatase deficiency 2899:Acta Paediatrica Scandinavica 2814:10.1016/S0065-2660(01)44087-9 2727:"Genomics and perinatal care" 2485:10.1016/S0925-4439(99)00074-5 2414:"Hexosaminidase A Deficiency" 2372:10.1016/S0021-9258(19)81396-0 2329:10.1080/19485565.1977.9988272 2160:10.1016/S0021-9258(18)37323-X 1617:Disorders of Lipid Metabolism 1434: 1202:classical/balance controversy 925: 866: 843:are pushed aside to increase 781:AB-variant GM2-gangliosidosis 469: 4491:Metachromatic leukodystrophy 4066:10.1182/blood-2008-03-140830 3841:10.1126/science.276.5311.428 3460:10.1126/science.165.3894.698 2866:10.1097/GIM.0b013e3181d5a669 2774:Marik, J J (13 April 2005). 2650:10.1212/WNL.0b013e318227b215 1421:adeno-associated virus (AAV) 1366:. This drug is a reversible 1302:Tay–Sachs disease exists in 1121:; this was also a period of 1070:History of Tay–Sachs disease 798: 394: 355:, who described in 1887 the 7: 4776:Neurodegenerative disorders 4554:Jansky–Bielschowsky disease 4027:10.1016/j.ymgme.2010.11.163 3703:10.1016/j.ymgme.2010.08.006 3503:10.1056/NEJM197007022830104 1352:substrate reduction therapy 1346:Substrate reduction therapy 1177:lysosomal storage disorders 998:, about 1 in 27 to 1 in 30 957: 702:inborn errors of metabolism 514: 437: 10: 4812: 4786:Lysosomal storage diseases 4313:Lysosomal storage diseases 4154:10.1038/s41591-021-01664-4 2102:10.1016/j.ajhg.2012.08.007 1870:10.1186/s13023-020-01354-3 1265:Enzyme replacement therapy 1260:Enzyme replacement therapy 1140: 1067: 1063: 870: 373:enzyme replacement therapy 104:Three to six months of age 54:in Tay–Sachs disease. The 4692: 4608: 4567: 4539: 4512: 4464: 4419: 4396: 4347: 4332: 3968:Journal of Neurochemistry 3876:10.1517/13543784.10.3.455 3553:10.1017/s0269889700003112 3135:10.1007/s00439-003-1072-8 2989:Sao Paulo Medical Journal 2674:Journal of Law and Health 2063:. John Wiley & Sons. 1614:Marinetti, G. V. (2012). 1372:glucosylceramide synthase 1165:polymerase chain reaction 1094:amaurotic familial idiocy 1040:Reproductive compensation 940:tricyclic antidepressants 886:Chorionic villus sampling 205: 197: 187: 176: 156: 139: 124: 116: 108: 100: 74: 62: 46: 37: 29: 24: 3907:Human Molecular Genetics 3756:10.1177/0300985810388522 3587:. Elsevier. 2001-10-10. 3166:Annals of Human Genetics 543:Tay–Sachs disease is an 375:as possible treatments. 4761:Lipid storage disorders 4325:Lipid storage disorders 4273:Genetics Home Reference 3413:The Jewish Encyclopedia 2520:10.1089/dna.1993.12.651 2241:10.1002/gepi.1370040203 1486:Genetics Home Reference 1083:differential diagnostic 669:has been demonstrated. 667:compound heterozygosity 558:Tay–Sachs results from 16:Human medical condition 4594:Sea-blue histiocytosis 3608:Kimura, Motoo (1983). 1965:(Suppl 3): S192–S195. 1648:Walker, Julie (2007). 1378:like GM2 ganglioside. 1112: 1054:linkage disequilibrium 1034:Heterozygote advantage 992:lipid storage diseases 984: 904:in vitro fertilization 841:retinal ganglion cells 708:function. Enzymes are 598:gene's protein product 590:splice phase mutations 540: 528: 183:, psychosocial support 158:Differential diagnosis 4771:Ashkenazi Jews topics 4407:Globotriaosylceramide 3387:10.1353/cjs.2006.0061 2743:10.1056/NEJMra1105043 2060:Pregnancy For Dummies 1396:Cord blood transplant 1222:directional selection 1218:Theodosius Dobzhansky 1107: 974: 730:hexosaminidase A 534: 522: 4791:Congenital disorders 4437:Niemann–Pick disease 3919:10.1093/hmg/8.6.1111 3734:Veterinary Pathology 2854:Genetics in Medicine 2559:10.1136/bjo.50.7.414 2508:DNA and Cell Biology 2229:Genetic Epidemiology 2008:Myerowitz R (1997). 1928:10.1212/wnl.31.7.787 1795:10.1212/wnl.40.1.145 853:Niemann–Pick disease 3452:1969Sci...165..698O 2860:(4 Suppl): S5–S14. 2153:(35): 18587–18589. 1732:on 27 November 2011 1535:"Tay Sachs Disease" 1482:"Tay–Sachs disease" 1409:blood–brain barrier 1288:cerebrospinal fluid 1281:blood–brain barrier 1255:Research directions 1226:balancing selection 1214:purifying selection 1137:Society and culture 1103:Jewish Encyclopedia 740:, that breaks down 606:founder populations 545:autosomal recessive 525:autosomal recessive 509:Friedreich's ataxia 287:autosomal recessive 133:autosomal recessive 96:, inability to move 4693:External resources 4501:Galactocerebroside 4373:GM2 gangliosidoses 4368:GM1 gangliosidoses 3651:10.1038/mt.2011.27 3541:Science in Context 3409:"Amaurotic Idiocy" 3259:Slatkin M (2004). 3055:2012-04-20 at the 2284:10.1007/BF00207048 1971:10.1007/PL00014401 1376:glycosphingolipids 1131:GM2 gangliosidosis 985: 912:sickle cell anemia 882:Prenatal diagnosis 861:hepatosplenomegaly 594:missense mutations 541: 529: 379:Signs and symptoms 299:GM2 gangliosidosis 4751:Tay–Sachs disease 4738: 4737: 4729:Tay–Sachs disease 4602: 4601: 4535: 4534: 4456:Gaucher's disease 4382:Tay–Sachs disease 4277:Tay–Sachs on NCBI 4266:Tay–Sachs disease 4015:Mol. Genet. Metab 3835:(5311): 428–431. 3639:Molecular Therapy 3619:978-0-521-23109-1 3594:978-0-08-049030-4 3584:Tay-Sachs Disease 3446:(3894): 698–700. 2823:978-0-12-017644-1 2806:Tay–Sachs Disease 2778:. eMedicine.com. 2596:Arq Bras Oftalmol 2457:978-0-632-04425-2 2070:978-1-119-97731-5 1652:Tay–Sachs Disease 1600:978-3-527-33189-5 1298:Jacob sheep model 1236:natural selection 1169:selective process 839:region where all 734:hydrolytic enzyme 255:inability to move 231:Tay–Sachs disease 228: 227: 141:Diagnostic method 25:Tay–Sachs disease 19:Medical condition 4803: 4606: 4605: 4452:Glucocerebroside 4441:SMPD1-associated 4377:Sandhoff disease 4345: 4344: 4334:Sphingolipidoses 4321:lipid metabolism 4306: 4299: 4292: 4283: 4282: 4242: 4241: 4239: 4238: 4223: 4217: 4216: 4214: 4213: 4207:The Conversation 4198: 4192: 4191: 4173: 4132: 4126: 4125: 4123: 4122: 4113:. 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October 2012. 1478: 1322:as in the human 1181:Ashkenazi Jewish 1008:French Canadians 857:Sandhoff disease 785:Sandhoff disease 641:French Canadians 487: – include 320:of southeastern 318:French Canadians 303:sphingolipidosis 274:, which codes a 262:genetic mutation 235:genetic disorder 163:Sandhoff disease 147:hexosaminidase A 69:Medical genetics 42: 22: 21: 4811: 4810: 4806: 4805: 4804: 4802: 4801: 4800: 4741: 4740: 4739: 4734: 4733: 4688: 4687: 4617: 4603: 4598: 4563: 4531: 4508: 4469: 4460: 4415: 4411:Fabry's disease 4392: 4352: 4336: 4328: 4310: 4251: 4246: 4245: 4236: 4234: 4231:The Independent 4225: 4224: 4220: 4211: 4209: 4199: 4195: 4142:Nature Medicine 4133: 4129: 4120: 4118: 4103: 4099: 4046: 4042: 4010: 4003: 3964: 3960: 3950: 3948: 3939: 3938: 3934: 3903: 3899: 3860: 3856: 3822: 3818: 3808: 3806: 3799:ALBC Newsletter 3791: 3787: 3747:10.1.1.819.2731 3730: 3726: 3685: 3676: 3631: 3627: 3620: 3606: 3602: 3595: 3581: 3580: 3576: 3537: 3533: 3522: 3518: 3487: 3483: 3436: 3432: 3422: 3420: 3407: 3406: 3402: 3371: 3364: 3328: 3324: 3306: 3302: 3257: 3253: 3208: 3201: 3162: 3158: 3118: 3107: 3070: 3063: 3057:Wayback Machine 3048: 3044: 3034: 3032: 3023: 3022: 3018: 2981: 2977: 2938: 2934: 2895: 2891: 2846: 2839: 2824: 2802: 2795: 2785: 2783: 2772: 2768: 2731:N. 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Med 2723: 2719: 2709: 2707: 2698: 2697: 2693: 2670: 2666: 2629: 2625: 2588: 2584: 2539: 2535: 2504: 2500: 2469: 2465: 2458: 2441: 2437: 2410: 2403: 2393: 2391: 2387: 2365:(34): 18563–7. 2354: 2348: 2344: 2311: 2307: 2268: 2264: 2225: 2221: 2184: 2180: 2139: 2135: 2082: 2078: 2071: 2055: 2051: 2006: 2002: 1955: 1951: 1908: 1904: 1849: 1845: 1822: 1818: 1779: 1775: 1765: 1763: 1752: 1745: 1735: 1733: 1720: 1719: 1706: 1695: 1679: 1675: 1668: 1646: 1639: 1628: 1612: 1608: 1601: 1585: 1578: 1563: 1562: 1558: 1548: 1546: 1533: 1532: 1505: 1495: 1493: 1480: 1479: 1442: 1437: 1417: 1398: 1384: 1348: 1340:clinical trials 1300: 1271:injections for 1262: 1257: 1197:(hybrid vigor). 1163:test (prior to 1145: 1139: 1101:edition of the 1072: 1066: 1020:Irish Americans 976:Founder effects 969: 960: 932:supportive care 928: 908:cystic fibrosis 875: 869: 849:Gaucher disease 801: 736:, found in the 726: 724:Pathophysiology 704:comes from how 517: 472: 450:deterioration, 440: 397: 381: 326:Old Order Amish 295:genetic testing 291:GM2 ganglioside 224: 181:Supportive care 151:genetic testing 84: 50:as seen in the 48:Cherry-red spot 20: 17: 12: 11: 5: 4809: 4799: 4798: 4793: 4788: 4783: 4778: 4773: 4768: 4763: 4758: 4753: 4736: 4735: 4732: 4731: 4720: 4709: 4697: 4696: 4694: 4690: 4689: 4686: 4685: 4674: 4663: 4649: 4634: 4618: 4613: 4612: 4610: 4609:Classification 4600: 4599: 4597: 4596: 4591: 4588:Wolman disease 4577: 4571: 4569: 4565: 4564: 4562: 4561: 4559:Batten disease 4556: 4551: 4545: 4543: 4537: 4536: 4533: 4532: 4530: 4529: 4527:Farber disease 4519: 4517: 4510: 4509: 4507: 4505:Krabbe disease 4498: 4493: 4484: 4482: 4481: 4480: 4477:leukodystrophy 4462: 4461: 4459: 4458: 4449: 4443: 4426: 4424: 4417: 4416: 4414: 4413: 4403: 4401: 4394: 4393: 4391: 4390: 4384: 4379: 4370: 4360: 4358: 4355:gangliosidoses 4342: 4330: 4329: 4309: 4308: 4301: 4294: 4286: 4280: 4279: 4274: 4262: 4257: 4250: 4249:External links 4247: 4244: 4243: 4218: 4193: 4148:(2): 251–259. 4127: 4097: 4040: 4001: 3958: 3943:. 5 May 2008. 3932: 3897: 3870:(3): 455–466. 3854: 3816: 3785: 3740:(3): 807–813. 3724: 3697:(4): 357–363. 3674: 3625: 3618: 3600: 3593: 3574: 3531: 3516: 3481: 3430: 3400: 3381:(3): 291–323. 3362: 3341:(9): 541–554. 3331:Sachs, Bernard 3322: 3300: 3277:10.1086/423146 3271:(2): 282–293. 3251: 3228:10.1086/373882 3222:(4): 812–822. 3199: 3172:(3): 275–281. 3156: 3129:(4): 366–376. 3123:Human Genetics 3105: 3084:(3): 256–261. 3061: 3042: 3016: 2995:(4): 146–149. 2975: 2948:(5): 875–877. 2932: 2889: 2837: 2822: 2793: 2766: 2717: 2691: 2680:(1): 121–140. 2664: 2623: 2582: 2553:(7): 414–420. 2533: 2514:(8): 651–665. 2498: 2463: 2456: 2435: 2401: 2342: 2316:Social Biology 2305: 2272:Human Genetics 2262: 2219: 2178: 2133: 2096:(4): 608–620. 2076: 2069: 2049: 2020:(3): 195–208. 2014:Human Mutation 2000: 1949: 1902: 1843: 1816: 1789:(1): 145–150. 1773: 1743: 1704: 1693: 1673: 1666: 1637: 1626: 1606: 1599: 1576: 1556: 1503: 1439: 1438: 1436: 1433: 1429:adverse events 1416: 1413: 1397: 1394: 1383: 1380: 1370:of the enzyme 1347: 1344: 1299: 1296: 1261: 1258: 1256: 1253: 1252: 1251: 1244:neutral theory 1229: 1206:Hermann Muller 1198: 1141:Main article: 1138: 1135: 1119:Eastern Europe 1068:Main article: 1065: 1062: 1050: 1049: 1046:Founder effect 1043: 1037: 1000:Ashkenazi Jews 988:Ashkenazi Jews 968: 965: 959: 956: 944:phenothiazines 927: 924: 923: 922: 915: 897: 871:Main article: 868: 865: 829:ophthalmoscope 800: 797: 725: 722: 678:biodegradation 645: 644: 638: 632: 613:Ashkenazi Jews 516: 513: 471: 468: 439: 436: 396: 393: 380: 377: 314:Ashkenazi Jews 280:hexosaminidase 226: 225: 223: 222: 217: 211: 209: 203: 202: 199: 195: 194: 191: 185: 184: 178: 174: 173: 167:Leigh syndrome 160: 154: 153: 145:Testing blood 143: 137: 136: 126: 122: 121: 118: 114: 113: 110: 106: 105: 102: 98: 97: 78: 72: 71: 66: 60: 59: 44: 43: 35: 34: 31: 27: 26: 18: 15: 9: 6: 4: 3: 2: 4808: 4797: 4794: 4792: 4789: 4787: 4784: 4782: 4779: 4777: 4774: 4772: 4769: 4767: 4766:Rare diseases 4764: 4762: 4759: 4757: 4754: 4752: 4749: 4748: 4746: 4730: 4726: 4725: 4721: 4719: 4715: 4714: 4710: 4708: 4704: 4703: 4699: 4698: 4695: 4691: 4684: 4680: 4679: 4675: 4673: 4669: 4668: 4664: 4662: 4659: 4655: 4654: 4650: 4648: 4644: 4643: 4639: 4635: 4633: 4629: 4628: 4624: 4620: 4619: 4616: 4611: 4607: 4595: 4592: 4589: 4585: 4581: 4578: 4576: 4573: 4572: 4570: 4566: 4560: 4557: 4555: 4552: 4550: 4547: 4546: 4544: 4542: 4538: 4528: 4524: 4521: 4520: 4518: 4516: 4511: 4506: 4502: 4499: 4497: 4494: 4492: 4488: 4485: 4483: 4478: 4475: 4474: 4473: 4468: 4463: 4457: 4453: 4450: 4447: 4444: 4442: 4438: 4435: 4434:phospholipid: 4431: 4430:Sphingomyelin 4428: 4427: 4425: 4423: 4422:sphingomyelin 4418: 4412: 4408: 4405: 4404: 4402: 4400: 4395: 4388: 4385: 4383: 4380: 4378: 4374: 4371: 4369: 4365: 4362: 4361: 4359: 4356: 4351: 4346: 4343: 4340: 4335: 4331: 4326: 4322: 4318: 4317:Inborn errors 4314: 4307: 4302: 4300: 4295: 4293: 4288: 4287: 4284: 4278: 4275: 4272: 4268: 4267: 4263: 4261: 4258: 4256: 4253: 4252: 4232: 4228: 4222: 4208: 4204: 4197: 4189: 4185: 4181: 4177: 4172: 4167: 4163: 4159: 4155: 4151: 4147: 4143: 4139: 4131: 4117:on 2018-07-05 4116: 4112: 4108: 4101: 4093: 4089: 4084: 4079: 4075: 4071: 4067: 4063: 4059: 4055: 4051: 4044: 4036: 4032: 4028: 4024: 4021:(3): 356–63. 4020: 4016: 4008: 4006: 3997: 3993: 3989: 3985: 3981: 3977: 3974:(S1): 54–55. 3973: 3969: 3962: 3946: 3942: 3936: 3928: 3924: 3920: 3916: 3912: 3908: 3901: 3893: 3889: 3885: 3881: 3877: 3873: 3869: 3865: 3858: 3850: 3846: 3842: 3838: 3834: 3830: 3829: 3820: 3804: 3800: 3796: 3789: 3781: 3777: 3773: 3769: 3765: 3761: 3757: 3753: 3748: 3743: 3739: 3735: 3728: 3720: 3716: 3712: 3708: 3704: 3700: 3696: 3692: 3691: 3683: 3681: 3679: 3670: 3666: 3661: 3656: 3652: 3648: 3644: 3640: 3636: 3629: 3621: 3615: 3611: 3604: 3596: 3590: 3586: 3585: 3578: 3570: 3566: 3562: 3558: 3554: 3550: 3546: 3542: 3535: 3527: 3520: 3512: 3508: 3504: 3500: 3496: 3492: 3485: 3477: 3473: 3469: 3465: 3461: 3457: 3453: 3449: 3445: 3441: 3434: 3418: 3414: 3410: 3404: 3396: 3392: 3388: 3384: 3380: 3376: 3369: 3367: 3357: 3352: 3348: 3344: 3340: 3336: 3332: 3326: 3318: 3314: 3310: 3304: 3296: 3292: 3287: 3282: 3278: 3274: 3270: 3266: 3262: 3255: 3247: 3243: 3238: 3233: 3229: 3225: 3221: 3217: 3213: 3206: 3204: 3195: 3191: 3187: 3183: 3179: 3175: 3171: 3167: 3160: 3152: 3148: 3144: 3140: 3136: 3132: 3128: 3124: 3116: 3114: 3112: 3110: 3101: 3097: 3092: 3087: 3083: 3079: 3075: 3068: 3066: 3058: 3054: 3051: 3046: 3030: 3029:Irish Central 3026: 3020: 3012: 3008: 3003: 2998: 2994: 2990: 2986: 2979: 2971: 2967: 2963: 2959: 2955: 2951: 2947: 2943: 2936: 2928: 2924: 2920: 2916: 2912: 2908: 2905:(6): 546–62. 2904: 2900: 2893: 2885: 2881: 2876: 2871: 2867: 2863: 2859: 2855: 2851: 2844: 2842: 2833: 2829: 2825: 2819: 2815: 2811: 2807: 2800: 2798: 2781: 2777: 2770: 2762: 2758: 2753: 2748: 2744: 2740: 2736: 2732: 2728: 2721: 2705: 2701: 2695: 2687: 2683: 2679: 2675: 2668: 2660: 2656: 2651: 2646: 2642: 2638: 2634: 2627: 2619: 2615: 2610: 2605: 2601: 2597: 2593: 2586: 2578: 2574: 2569: 2564: 2560: 2556: 2552: 2548: 2544: 2537: 2529: 2525: 2521: 2517: 2513: 2509: 2502: 2494: 2490: 2486: 2482: 2478: 2474: 2467: 2459: 2453: 2449: 2445: 2444:Korf, Bruce R 2439: 2431: 2427: 2423: 2419: 2415: 2408: 2406: 2386: 2382: 2378: 2373: 2368: 2364: 2360: 2353: 2346: 2338: 2334: 2330: 2326: 2323:(2): 117–34. 2322: 2318: 2317: 2309: 2301: 2297: 2293: 2289: 2285: 2281: 2277: 2273: 2266: 2258: 2254: 2250: 2246: 2242: 2238: 2234: 2230: 2223: 2215: 2211: 2206: 2201: 2197: 2193: 2189: 2182: 2174: 2170: 2166: 2161: 2156: 2152: 2148: 2144: 2137: 2129: 2125: 2120: 2115: 2111: 2107: 2103: 2099: 2095: 2091: 2087: 2080: 2072: 2066: 2062: 2061: 2053: 2045: 2041: 2037: 2033: 2028: 2023: 2019: 2015: 2011: 2004: 1996: 1992: 1988: 1984: 1980: 1976: 1972: 1968: 1964: 1960: 1953: 1945: 1941: 1937: 1933: 1929: 1925: 1922:(7): 787–98. 1921: 1917: 1913: 1906: 1898: 1894: 1889: 1884: 1880: 1876: 1871: 1866: 1862: 1858: 1854: 1847: 1839: 1835: 1832:(8): 347–53. 1831: 1827: 1820: 1812: 1808: 1804: 1800: 1796: 1792: 1788: 1784: 1777: 1761: 1757: 1750: 1748: 1731: 1727: 1723: 1717: 1715: 1713: 1711: 1709: 1700: 1696: 1694:9783662033562 1690: 1686: 1685: 1677: 1669: 1667:9781404206977 1663: 1659: 1654: 1653: 1644: 1642: 1633: 1629: 1627:9781461595649 1623: 1619: 1618: 1610: 1602: 1596: 1592: 1591: 1583: 1581: 1572: 1571: 1566: 1560: 1544: 1540: 1536: 1530: 1528: 1526: 1524: 1522: 1520: 1518: 1516: 1514: 1512: 1510: 1508: 1491: 1487: 1483: 1477: 1475: 1473: 1471: 1469: 1467: 1465: 1463: 1461: 1459: 1457: 1455: 1453: 1451: 1449: 1447: 1445: 1440: 1432: 1430: 1426: 1422: 1412: 1410: 1405: 1403: 1393: 1390: 1389:pyrimethamine 1379: 1377: 1373: 1369: 1365: 1360: 1357: 1353: 1343: 1341: 1337: 1333: 1329: 1325: 1321: 1317: 1313: 1309: 1305: 1295: 1293: 1289: 1284: 1282: 1278: 1274: 1270: 1266: 1249: 1248:genetic drift 1245: 1241: 1237: 1233: 1230: 1227: 1223: 1219: 1215: 1211: 1207: 1203: 1199: 1196: 1192: 1189: 1188: 1187: 1184: 1182: 1178: 1174: 1173:heterozygotes 1170: 1166: 1162: 1157: 1155: 1151: 1144: 1134: 1132: 1126: 1124: 1120: 1116: 1111: 1106: 1104: 1099: 1098:Gregor Mendel 1095: 1090: 1086: 1084: 1080: 1079:Bernard Sachs 1076: 1071: 1061: 1059: 1055: 1047: 1044: 1041: 1038: 1035: 1032: 1031: 1030: 1027: 1025: 1024:heterozygotes 1021: 1017: 1014:community of 1013: 1009: 1005: 1001: 997: 996:United States 993: 989: 981: 977: 973: 964: 955: 953: 949: 945: 941: 937: 933: 920: 916: 913: 909: 905: 901: 898: 895: 894:Amniocentesis 891: 887: 883: 880: 879: 878: 874: 864: 862: 858: 854: 850: 846: 845:visual acuity 842: 838: 834: 830: 826: 822: 818: 814: 810: 806: 796: 794: 790: 786: 782: 778: 774: 770: 766: 762: 758: 753: 751: 747: 743: 742:sphingolipids 739: 735: 731: 721: 719: 714: 711: 707: 703: 699: 694: 691: 687: 683: 679: 675: 670: 668: 663: 658: 657:polymorphisms 654: 650: 642: 639: 636: 633: 630: 626: 625:reading frame 622: 619:insertion in 618: 614: 611: 610: 609: 607: 603: 599: 595: 591: 587: 583: 580: 576: 572: 571:chromosome 15 568: 565: 561: 556: 554: 550: 546: 538: 533: 526: 521: 512: 510: 504: 502: 498: 494: 493:schizophrenia 490: 486: 482: 478: 467: 465: 461: 457: 453: 449: 445: 435: 433: 429: 425: 421: 417: 413: 412:deterioration 409: 405: 401: 392: 390: 387: 376: 374: 370: 366: 362: 358: 354: 353:Bernard Sachs 350: 346: 341: 339: 335: 331: 327: 323: 319: 315: 311: 306: 304: 300: 296: 292: 288: 284: 281: 277: 273: 272:chromosome 15 269: 268: 263: 258: 256: 252: 248: 244: 240: 236: 232: 221: 220:Bernard Sachs 218: 216: 213: 212: 210: 208: 204: 200: 196: 192: 190: 186: 182: 179: 175: 172: 168: 164: 161: 159: 155: 152: 148: 144: 142: 138: 134: 130: 127: 123: 119: 115: 111: 107: 103: 99: 95: 91: 87: 82: 79: 77: 73: 70: 67: 65: 61: 57: 53: 49: 45: 41: 36: 32: 28: 23: 4722: 4711: 4700: 4676: 4665: 4651: 4636: 4621: 4472:sulfatidoses 4433: 4381: 4264: 4235:. Retrieved 4233:. 2022-02-18 4230: 4221: 4210:. Retrieved 4206: 4196: 4145: 4141: 4130: 4119:. Retrieved 4115:the original 4110: 4100: 4057: 4053: 4043: 4018: 4014: 3971: 3967: 3961: 3949:. Retrieved 3935: 3910: 3906: 3900: 3867: 3863: 3857: 3832: 3826: 3819: 3807:. Retrieved 3798: 3788: 3737: 3733: 3727: 3694: 3688: 3642: 3638: 3628: 3609: 3603: 3583: 3577: 3544: 3540: 3534: 3525: 3519: 3497:(1): 15–20. 3494: 3490: 3484: 3443: 3439: 3433: 3421:. Retrieved 3412: 3403: 3378: 3374: 3338: 3334: 3325: 3316: 3312: 3303: 3268: 3264: 3254: 3219: 3215: 3169: 3165: 3159: 3126: 3122: 3081: 3077: 3045: 3033:. Retrieved 3028: 3019: 2992: 2988: 2978: 2945: 2941: 2935: 2902: 2898: 2892: 2857: 2853: 2805: 2784:. Retrieved 2769: 2737:(1): 64–73. 2734: 2730: 2720: 2708:. Retrieved 2694: 2677: 2673: 2667: 2640: 2636: 2626: 2602:(4): 537–9. 2599: 2595: 2585: 2550: 2546: 2536: 2511: 2507: 2501: 2476: 2472: 2466: 2447: 2438: 2418:GeneReviews 2417: 2392:. Retrieved 2362: 2358: 2345: 2320: 2314: 2308: 2278:(1): 83–87. 2275: 2271: 2265: 2235:(2): 77–85. 2232: 2228: 2222: 2195: 2191: 2181: 2150: 2146: 2136: 2093: 2089: 2079: 2059: 2052: 2017: 2013: 2003: 1962: 1958: 1952: 1919: 1915: 1905: 1860: 1856: 1846: 1829: 1825: 1819: 1786: 1782: 1776: 1764:. Retrieved 1734:. Retrieved 1730:the original 1683: 1676: 1651: 1616: 1609: 1589: 1568: 1559: 1547:. Retrieved 1538: 1494:. Retrieved 1485: 1418: 1415:Gene therapy 1406: 1399: 1385: 1361: 1349: 1331: 1323: 1307: 1301: 1285: 1276: 1263: 1240:Motoo Kimura 1185: 1161:enzyme assay 1158: 1146: 1127: 1113: 1108: 1093: 1091: 1087: 1073: 1051: 1028: 986: 967:Epidemiology 961: 929: 919:Dor Yeshorim 876: 805:enzyme assay 802: 754: 727: 695: 689: 685: 682:gangliosides 673: 671: 661: 646: 628: 585: 563: 557: 542: 536: 505: 473: 441: 422:, unable to 398: 386:neurological 382: 369:gene therapy 365:tuberculosis 342: 336:of southern 330:Pennsylvania 307: 265: 259: 251:hearing loss 230: 229: 94:hearing loss 85: 80: 4702:MedlinePlus 4515:sphingosine 4364:Ganglioside 4350:ganglioside 3356:10192/32703 3035:13 February 1570:Mayo Clinic 1316:nucleotides 1304:Jacob sheep 1283:in humans. 1058:coalescence 983:population. 952:risperidone 948:haloperidol 813:fibroblasts 789:active site 649:biochemical 481:adolescence 448:motor skill 406:. Then, as 243:spinal cord 207:Named after 101:Usual onset 30:Other names 4745:Categories 4724:Patient UK 4678:DiseasesDB 4387:AB variant 4237:2022-03-07 4212:2022-03-07 4121:2018-05-20 3309:Tay, Waren 2643:(5): e34. 1912:Desnick RJ 1435:References 1402:cord blood 1154:counseling 980:population 926:Management 867:Prevention 817:leukocytes 761:glycolipid 757:hydrolysis 750:blood test 746:fatty acid 602:have shown 501:wheelchair 470:Late-onset 464:spasticity 452:dysarthria 332:, and the 310:supportive 4713:eMedicine 4549:Infantile 4487:Sulfatide 4467:sulfatide 4399:globoside 4188:246748772 4162:1078-8956 4074:0006-4971 3996:221872176 3988:0022-3042 3764:0300-9858 3742:CiteSeerX 3711:1096-7192 3395:143784985 2942:Neurology 2637:Neurology 2110:0002-9297 1979:1432-1076 1916:Neurology 1879:1750-1172 1863:(1): 92. 1783:Neurology 1368:inhibitor 1364:miglustat 1356:sialidase 1210:wild type 1195:heterosis 1075:Waren Tay 1016:Louisiana 1004:incidence 994:. In the 890:gestation 833:choroidal 799:Diagnosis 773:lysosomes 738:lysosomes 718:phenotype 716:abnormal 713:catalysts 698:wild-type 653:sequenced 617:base pair 615:. A four 579:lysosomal 560:mutations 497:psychosis 485:adulthood 483:or early 456:dysphagia 444:cognitive 432:paralytic 428:atrophied 395:Infantile 345:Waren Tay 338:Louisiana 215:Waren Tay 198:Frequency 189:Prognosis 177:Treatment 112:Long term 81:Initially 64:Specialty 4718:ped/3016 4523:Ceramide 4339:ceramide 4180:35145305 4171:10786171 4092:18587012 4035:21185210 3951:10 April 3945:Archived 3927:10332044 3884:11227045 3803:Archived 3772:21123862 3719:20817517 3669:21487393 3569:31003675 3561:15168671 3417:Archived 3319:: 55–57. 3295:15208782 3246:12612865 3194:23470984 3151:10768286 3143:14727180 3053:Archived 3011:11500789 2970:37096876 2962:16966555 2927:86246245 2884:20393311 2832:11596991 2780:Archived 2761:22216843 2704:Archived 2686:10182027 2659:21810694 2618:19820796 2493:10571007 2446:(2000). 2430:Archived 2426:20301397 2385:Archived 2300:19278804 2257:23770703 2173:Archived 2128:22981120 2044:22587938 1987:11216898 1944:27305940 1897:32295606 1811:19301606 1766:24 April 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400:Infants 278:of the 276:subunit 264:in the 129:Genetic 4707:001417 4661:272750 4658:272800 4446:type C 4186: 4178: 4168: 4160: 4090: 4080: 4072: 4033: 3994: 3986: 3925: 3890: 3882: 3847: 3778: 3770: 3762: 3744: 3717: 3709: 3667: 3657: 3616: 3591: 3567: 3559: 3509: 3474: 3466: 3393: 3293: 3283: 3244: 3234: 3192: 3184: 3149: 3141: 3100:677122 3098: 3088: 3009: 2968: 2960: 2925: 2917: 2882: 2872: 2830: 2820: 2786:10 May 2759: 2749: 2684: 2657: 2616: 2575: 2568:506244 2565: 2526: 2491: 2454: 2424: 2394:11 May 2379: 2337:897699 2335: 2298: 2290: 2255: 2247: 2212: 2202: 2167: 2126: 2116: 2108: 2067: 2042: 2034: 1993: 1985: 1977: 1942: 1934: 1895: 1885: 1877: 1836: 1809: 1801: 1736:10 May 1691: 1664: 1624: 1597: 1549:29 May 1496:29 May 1150:Israel 950:, and 855:, and 837:foveal 825:retina 821:macula 635:Cajuns 582:enzyme 495:-like 489:speech 462:, and 460:ataxia 430:, and 361:allele 349:retina 334:Cajuns 324:, the 322:Quebec 283:enzyme 253:, and 125:Causes 52:retina 4683:12916 4647:330.1 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