Tay Sachs Disease

NORD gratefully acknowledges Michael M. Kaback, MD, Professor, Pediatric & Reproductive Medicine (emeritus), University of California, San Diego School of Medicine, for assistance in the preparation of this report.

Synonyms of Tay Sachs Disease

B Variant GM2-Gangliosidosis
GM2 Gangliosidosis, Type 1
Hexoaminidase Alpha-Subunit Deficiency (Variant B)
Hexosaminidase A deficiency
HEXA deficiency
Sphingolipidosis, Tay-Sachs
TSD

Subdivisions of Tay Sachs Disease

Infantile Tay-Sachs Disease
Juvenile (Subacute) Tay-Sachs Disease
Late-Onset Tay-Sachs Disease

General Discussion

Tay-Sachs disease is a rare, neurodegenerative disorder in which deficiency of an enzyme (hexosaminidase A) results in excessive accumulation of certain fats (lipids) known as gangliosides in the brain and nerve cells. This abnormal accumulation of gangliosides leads to progressive dysfunction of the central nervous system. This disorder is categorized as a lysosomal storage disease. Lysosomes are the major digestive units in cells. Enzymes within lysosomes break down or "digest" nutrients, including certain complex carbohydrates and fats. When an enzyme like hexosaminidase A, which are needed to breakdown certain substances like fats, are missing or ineffective, they build up in the lysosomal. This is called abnormal “storage”. When too much fatty material builds up in the lysosome, it becomes toxic destroying the cell and damaging surrounding tissue.

Symptoms associated with Tay-Sachs disease may include an exaggerated startle response to sudden noises, listlessness, loss of previously acquired skills (i.e., psychomotor regression), and severely diminished muscle tone (hypotonia). Infants with hypotonia may be described as “floppy”. As the disease progresses, affected infants and children may develop cherry-red spots within the middle layer of the eyes, gradual loss of vision, and hearing loss, increasing muscle stiffness and restricted movements (spasticity), eventual paralysis, uncontrolled electrical disturbances in the brain (seizures), and deterioration of cognitive processes (dementia). The classical form of Tay-Sachs disease occurs during infancy. This is the most common form and is usually fatal during early childhood. There are also juvenile and adult forms of Tay-Sachs disease, but these are rare. Children with the juvenile form, also called the subacute form, develop symptoms later than those with the infantile form, and they usually live until later in childhood or adolescence. The adult form, also called late-onset Tay-Sachs disease, may occur anytime from adolescence to the mid-30s. The symptoms and severity can vary from one person to another. Some people may fall in between the juvenile and adult forms.

Tay-Sachs disease is inherited in an autosomal recessive manner. The disorder results from changes (mutations) of a gene known as the HEXA gene, which regulates production of the hexosaminidase A enzyme. The HEXA gene has been mapped to the long arm (q) of chromosome 15 (15q23-q24). There is no cure for Tay-Sachs disease, and the treatment is aimed at relieving the specific symptoms that occur.

Another name for Tay-Sachs disease is GM2 gangliosidosis type 1. There are two other, related disorders, called Sandhoff disease and hexosaminidase activator deficiency that are indistinguishable from Tay-Sachs disease based on symptoms and can only be differentiated through testing to determine the underlying cause. These two disorders are also cause reduced activity of hexosaminidase, but are caused by changes in different genes. Collectively, these three disorders are known as GM2 gangliosidoses.

Signs & Symptoms

Tay-Sachs disease is broken down into the classic or infantile form, the juvenile form, and the adult or late-onset form. In individuals with infantile Tay-Sachs disease, symptoms typically first appear between three and five months of age. In individuals with the late-onset form, symptoms may become apparent anytime from adolescence through the mid-30s.

Infantile Tay-Sachs Disease
The infantile form of Tay-Sachs disease is characterized by an almost complete lack of hexosaminidase A enzyme activity. The disorder often progresses rapidly, resulting in significant mental and physical deterioration.

Infants may appear completely unaffected at birth. Initial symptoms, which usually develop between 3 and 6 months, can include mild muscle weakness, twitching or jerking of muscles (myoclonic jerks), and an exaggerated startle response, such as when there is a sudden or unexpected noise. The startle response may be partly due to an increased sensitivity to sound (acoustic hypersensitivity).

Between six and 10 months, affected infants may fail to gain new motor skills. They may no longer make eye contact and there may be unusual eye movements. They may be listlessness and irritable. As affected infants age, they may experience slow growth, progressive muscle weakness, diminished muscle tone (hypotonia), and diminished mental functioning. Affected infants may also exhibit gradual loss of vision, involuntary muscle spasms that result in slow, stiff movements (spasticity), and the loss of previously acquired skills (i.e., psychomotor regression) such as crawling or sitting up.

A characteristic symptom of Tay-Sachs disease is the development of cherry red spots in the eyes. This condition occurs when the macular cells of the eye deteriorate, exposing the underlying choroid. The choroid is the middle layer of the eye that consists of blood vessels that supply blood to the retina. This characteristic finding occurs is approximately 90% of individuals with Tay-Sachs disease.

As affected infants age, more serious complications may develop, including seizures; difficulty swallowing; progressive hearing loss; confusion, disorientation, and/or deterioration of intellectual abilities (dementia); paralysis; and continued loss of vision, which can be rapid and lead to blindness. Eventually, infants may become unresponsive to their environment and surroundings. By three to five years of age, life-threatening complications may occur such as respiratory failure.

Juvenile (Subacute) Tay-Sachs Disease
The onset of this form can be anywhere between two and 10 years of age. Often, one of the first signs is clumsiness and problems with coordination. This occurs because affected children have issues controlling their body’s movements (ataxia). Behavioral problems a progressive loss of speech, life skills, and intellectual abilities also develop. Children may or may not develop a cherry-red spot in the eyes. Degeneration of the nerve that carries impulses from the eye to the brain to form images (optic atrophy) may occur. Some children may have retinitis pigmentosa, a large group of vision disorders that cause progressive degeneration of the retina, the light-sensitive membrane that coats the inside of the eyes. Children will become less responsive to their environment and surroundings. Life-threatening complications usually occur around 15 years of age.

Late-Onset Tay-Sachs Disease
The symptoms associated with late-onset Tay-Sachs disease vary greatly from one person to another. Affected individuals will not have all the symptoms listed below. The disorder progresses much slower than the infantile form. The variability of late onset Tay-Sachs may even be seen in members of the same family. One person may have symptoms in their 20s, while another reaches theirs 60s or 70s with only minor problems with their muscles.

Initial symptoms associated with late-onset Tay-Sachs disease may include clumsiness, mood alterations, and progressive muscle weakness and wasting (amyotrophy). As affected individuals age, they may exhibit tremors, muscle twitching (fasciculations), seizures, slurred speech (dysarthria), an inability to coordinate voluntary movements (ataxia), difficulty swallowing (dysphagia), and a condition known as dystonia. Dystonia is a group of disorders characterized by involuntary muscle contractions that may force certain body parts into unusual, and sometimes painful, movements and positions. Some individuals may have involuntary muscle spasms that result in slow, stiff movements (spasticity).

As late-onset Tay-Sachs disease progresses, affected individuals may experience problems with walking, running, and other similar activities. In severe instances, affected individuals may eventually need assistive devices such as braces or a wheelchair.

In some instances, affected individuals may experience mental deterioration, memory problems, and behavioral changes including short attention spans and personality changes. In approximately 40% of people, psychiatric episodes including loss of contact with reality, paranoia, hallucinations, bipolar episodes, and depression may be present.

Causes

Tay-Sachs disease is caused by a change (mutation) in the hexosaminidase subunit alpha (HEXA) gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the protein, this can affect many organ systems of the body, including the brain.

The HEXA gene regulates the production of the enzyme hexosaminidase A. More than 80 different mutations of the HEXA gene have been identified in individuals with the disease. Inheriting two mutated copies of the HEXA gene (homozygotes) causes deficiency of the hexosaminidase A enzyme, which is necessary to breakdown fatty substance (lipid) known as GM2-ganglioside within cells of the body. Failure to breakdown GM2-ganglioside results in its abnormal accumulation in brain and nerve cells eventually resulting in the progressive deterioration of the central nervous system.

In infantile Tay-Sachs disease, there is an almost complete lack of hexosaminidase A. In late-onset Tay-Sachs disease, there is deficiency of hexosaminidase A enzyme activity. Because there is some enzyme activity, the disorder is less severe and progresses much slower than infantile Tay-Sachs disease. The exact amount of enzyme activity in late-onset Tay-Sachs disease varies greatly from one person to another. Consequently, the age of onset, severity, specific symptoms, and rate of progression of late-onset Tay-Sachs disease also vary greatly from one person to another.

The changes in the HEXA gene that cause Tay-Sachs disease are inherited in an autosomal recessive manner. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.

Researchers have determined that the gene for Tay-Sachs disease is located on the long arm (q) of chromosome 15 (15q23-q24). Chromosomes are located in the nucleus of human cells and carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes numbered from 1 through 22 are called autosomes and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Affected Populations

Tay-Sachs disease affects males and females in equal numbers. Tay-Sachs disease occurs with greater frequency among Jewish people of Ashkenazi descent, i.e. those of Eastern or Central European descent. Approximately one in 30 Ashkenazi Jewish people carries the altered gene for Tay-Sachs disease. In addition, one in 300 individuals of non-Ashkenazi Jewish heritage is a carrier.

In this specific Jewish population, about one in 3,600 live births is affected. The disease has also been reported in some individuals of Italian, Irish Catholic, and non-Jewish French Canadian descent, especially those living in the Cajun community of Louisiana and the southeastern Quebec. In the general population, the carrier rate for the altered gene is approximately 1 in 250-300 people.

Late-onset Tay-Sachs disease occur less often than the infantile form. However, rare disorders like late-onset Tay-Sachs disease often go unrecognized. These disorders are under-diagnosed, making it difficult to determine the true frequency of such disorders in the general population.

Related Disorders

Symptoms of the following disorders can be similar to those of Tay-Sachs disease. Comparisons may be useful for a differential diagnosis:

Sandhoff disease is a rare genetic disorder resulting in the progressive deterioration of the central nervous system (neurodegenerative disorder). A deficiency of the enzymes hexosaminidase A and B results in the accumulation of certain fats (lipids) in the brain and other organs of the body. This disorder is categorized as a lysosomal storage disease. The most common form affects infants, usually beginning between three and six months of age. Symptoms in infants may include feeding problems, general weakness, and an exaggerated startle reflex in response to sudden loud noise. Motor delays, loss of previously acquired skills, and intellectual impairment are progressive. Children can experience hearing loss, vision loss, and seizures. There are very rare forms where symptoms begin later in childhood, adolescence or adulthood. Sandhoff disease is a severe form of Tay-Sachs disease and is not limited to any specific ethnic group. Sandhoff disease is caused by changes (mutations) in the hexosaminidase B (HEXB) gene and is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Sandhoff” as your search term in the Rare Disease Database.)

Leigh syndrome is a rare genetic neurometabolic disorder. It is characterized by the degeneration of the central nervous system (i.e., brain, spinal cord, and optic nerve). The symptoms of Leigh syndrome usually begin between the ages of three months and two years, but some patients do not exhibit signs and symptoms until several years later. Symptoms are associated with progressive neurological deterioration and may include loss of previously acquired motor skills, loss of appetite, vomiting, irritability, and/or seizure activity. As Leigh syndrome progresses, symptoms may also include generalized weakness, lack of muscle tone (hypotonia), and episodes of lactic acidosis, which may lead to impairment of respiratory and kidney function. Several different genetically determined enzyme defects can cause the syndrome, initially described more than 60 years ago. Most individuals with Leigh syndrome have defects of mitochondrial energy production, such as deficiency of an enzyme of the mitochondrial respiratory chain complex or the pyruvate dehydrogenase complex. In most people, Leigh syndrome is inherited as an autosomal recessive trait. However, X-linked recessive and maternal inheritance, due to a mitochondrial DNA mutation, are additional modes of transmission. (For more information on this disorder, choose “Leigh” as your search term in the Rare Disease Database.)

The neuronal ceroid lipofuscinoses (NCLs) are a group of progressive degenerative neurometabolic diseases. These diseases share certain similar symptoms and are distinguished in part by the age at which such symptoms appear. Two forms occur during infancy: classic infantile CLN1 disease (Santavuori disease) and CLN2 disease (late infantile type). The NCLs are characterized by abnormal accumulation of certain fatty, granular substances (i.e., pigmented lipids [lipopigments] ceroid and lipofuscin) within nerve cells (neurons) of the brain as well as other tissues of the body that may result in progressive deterioration (atrophy) of certain areas of the brain, neurological impairment, and other characteristic symptoms and physical findings. (For more information, choose the specific disorder name as your search term in the Rare Disease Database.)

Tay-Sachs disease is classified as a lysosomal storage disease. Several other lysosomal storage diseases can share symptoms similar to those seen in Tay-Sachs disease. Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies. There are nearly 50 of these disorders altogether, and they may affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system. New lysosomal storage disorders continue to be identified. While clinical trials are in progress on possible treatments for some of these diseases, there is currently no approved treatment for many lysosomal storage diseases. (For more information on this disorder, choose “lysosomal” as your search term in the Rare Disease Database.)

Symptoms of the following disorders can be similar to those of late-onset Tay-Sachs disease. Comparisons may be useful for a differential diagnosis:

Adult neuronal ceroid lipofuscinosis (ANCL) is a general term for several rare genetic disorders that belong to a group of progressive, degenerative neurometabolic disorders known as the neuronal ceroid lipofuscinoses (NCLs). These disorders share certain similar symptoms and are distinguished in part by the age at which such symptoms appear. Onset of ANCL is usually around the age of 30, but these disorders can occur during the teen-aged years or in people more than 50 years old. The NCLs as a group are characterized by abnormal accumulation of certain fatty, granular substances (i.e., pigmented lipids [lipopigments] ceroid and lipofuscin) within nerve cells (neurons) of the brain as well as other tissues of the body. This is accompanied by progressive deterioration (atrophy) of certain areas of the brain, neurological impairment, and other characteristic symptoms and physical findings. ANCL is sometimes called Kufs disease. Historically, Kufs disease was broken down into Type A or Type B. The ANCLs are caused by changes (mutations) in different genes and can have different signs and symptoms. (For more information on this disorder, choose “adult neuronal ceroid lipofuscinosis” as your search term in the Rare Disease Database.)

Amyotrophic lateral sclerosis (ALS) is characterized by slight muscle weakness, clumsy hand movements, and/or difficulty performing tasks that require delicate movements of the fingers and/or hands. Muscular weakness in the legs may cause tripping and falling. People with ALS may have difficulty swallowing (dysphagia), and speech may be slowed. Additional symptoms of this disorder include progressive weakness of the lips and impairment and/or loss of function of the tongue, mouth, and/or voice box (bulbar symptoms). Leg cramps may occur during the night, most frequently in the calf and/or thigh muscles. ALS may progress quickly or slowly, and gradually additional muscles become involved. Individuals with ALS may also exhibit uncontrolled twitching of muscles (fasciculations), stiffness in the legs, and/or coughing. As the ability to move becomes progressively impaired, people with this disease are at increased risk for respiratory failure. The exact cause of ALS is unknown. (For more information on this disorder, choose “Amyotrophic Lateral Sclerosis” as your search term in the Rare Disease Database.)

Diagnosis

The diagnosis of Tay-Sachs disease may be confirmed by a thorough clinical evaluation and specialized tests, such as blood tests that measure the levels of hexosaminidase A in the body. Hexosaminidase A is reduced in people with Tay-Sachs disease, and absent or nearly absent in the infantile form.

Molecular genetic testing can confirm a diagnosis of Tay-Sachs disease. Molecular genetic testing can detect mutations in the HEXA gene known to cause the disorder, but is available only as a diagnostic service at specialized laboratories.

In some instances, it is possible that a diagnosis of Tay-Sachs disease may be suspected before birth (prenatally) based upon specialized tests, such as amniocentesis and chorionic villus sampling (CVS). During amniocentesis, a sample of fluid that surrounds the developing fetus is removed, while CVS involves the removal of tissue samples from a portion of the placenta. These samples are studied to determine whether hexosaminidase A is present or, as in people with Tay-Sachs disease, absent or present in greatly reduced levels. This is called an enzyme assay. Prenatal diagnosis is also possible through molecular genetic testing of tissue samples obtained through CVS or amniocentesis if the specific disease-causing mutation in the HEXA gene is known in the family.

Blood tests can determine whether individuals are carriers for Tay-Sachs disease (i.e., they have one copy of the disease gene). Relatives of individuals with Tay-Sachs disease should be tested to determine whether they are carriers of the disease gene. Couples who are planning to have a child and have any Jewish ancestry (not just Ashkenazi) are encouraged to undergo carrier screening before proceeding with a pregnancy.

Standard Therapies

Treatment

There is no specific treatment for Tay-Sachs disease. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, speech pathologists, specialists who asses and treat hearing problems (audiologists), eye specialists, and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment. Genetic counseling may be of benefit for affected individuals and their families. Psychosocial support is recommended for the entire family.

Because of the potential of feeding difficulties, infants should be monitored for nutritional status and proper hydration. Nutritional support and supplementation may be necessary and, sometimes, the insertion of a feeding tube may be necessary. In addition to nutritional support, a feeding tube may be necessary to help prevent food, liquid or other foreign material from accidently going into the lungs (aspiration).

Anticonvulsants may be used to treat seizures associated in some people with Tay-Sachs disease, but may not be effective in all people. Also, the type and frequency of seizures can change in a person, which will require a change in medication type or dosage.

Investigational Therapies

Research is ongoing to develop enzyme replacement therapy (ERT) for Tay-Sachs disease. Enzyme replacement therapy involves replacing a missing enzyme in individuals who are deficient or lack a particular enzyme. Synthetic versions of missing enzymes have been developed and used to treat individuals with other lysosomal storage diseases including Hurler syndrome, Fabry syndrome, and Gaucher disease. However, ERT has not proven successful in people with Tay-Sachs disease. One issue is the inability to find a way for the replacement enzyme to cross the blood-brain barrier, a protective networks of blood vessels and cells that allow some materials to enter the brain, while keeping other materials out.

Gene therapy is also being studied as another possible approach to therapy for some lysosomal storage disorders. In gene therapy, the defective gene present in a patient is replaced with a normal gene to enable the production of active enzyme and prevent the development and progression of the disease in question. Given the permanent transfer of the normal gene, which can produce active enzyme at all sites of disease, this form of therapy is theoretically most likely to lead to a “cure.” However, at this time, there are still technical difficulties to resolve before gene therapy can succeed.

Chaperone therapy is also being studied for Tay-Sachs disease. This type of therapy involves very small molecules that attach to newly-created hexosaminidase A enzymes, before the mutated enzymes are broken down, and guides them to the lysosome, where the enzymes can perform their normal function. Such a molecule can also cross the blood-brain barrier. This therapy is only in initial stages of study, and more research will necessary to determine its long-term safety and effectiveness.

A drug called pyrimethamine has been tried as a treatment for Tay-Sachs disease. Affected individuals who took the medication showed increased activity of hexosaminidase A. However, this increased activity did not lead to any noticeable improvement in neurological or psychiatric symptoms. More research is necessary to determine whether pyrimethamine has any role in the treatment of Tay-Sachs disease.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact: www.centerwatch.com

For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

Resources

Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.

NORD Member Organizations

National Tay-Sachs and Allied Diseases Association, Inc.
- 2001 Beacon Street
- 204
- Brookline, MA 02146-4227 USA
- Phone: (617) 277-4463
- Toll-free: (800) 906-8723
- Email: info@ntsad.org
- Website: http://www.NTSAD.org

Other Organizations

Genetic and Rare Diseases (GARD) Information Center
- PO Box 8126
- Gaithersburg, MD 20898-8126
- Phone: (301) 251-4925
- Toll-free: (888) 205-2311
- Website: http://rarediseases.info.nih.gov/GARD/
Let Them Hear Foundation
- 1900 University Avenue, Suite 101
- East Palo Alto, CA 94303
- Phone: (650) 462-3174
- Email: info@letthemhear.org
- Website: http://www.letthemhear.org
March of Dimes
- 1275 Mamaroneck Avenue
- White Plains, NY 10605
- Phone: (914) 997-4488
- Email: AskUs@marchofdimes.org or preguntas@nacersano.org
- Website: http://www.marchofdimes.org and nacersano.org
Metabolic Support UK
- 5 Hilliards Court, Sandpiper Way
- Chester Business Park
- Chester, CH4 9QP United Kingdom
- Phone: 0124420758108452412173
- Email: contact@metabolicsupportuk.org
- Website: https://www.metabolicsupportuk.org/
The Arc
- 1825 K Street NW, Suite 1200
- Washington, DC 20006
- Phone: (202) 534-3700
- Toll-free: (800) 433-5255
- Email: info@thearc.org
- Website: http://www.thearc.org
Vaincre Les Maladies Lysosomales
- 2 Ter Avenue
- Massy, 91300 France
- Phone: 169754030
- Email: accueil@vml-asso.org
- Website: http://www.vml-asso.org

References

JOURNAL ARTICLES
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Steiner KM, Brenck J, Goericke S, Timmann D. Cerebellar atrophy and muscle weakness: late-onset Tay-Sachs disease outside Jewish populations. BMJ Case Rep. 2016;2016. https://www.ncbi.nlm.nih.gov/pubmed/27033294

Osher E, Fattal-Valevski A, Sagie L, et al. Effect of cyclic, low dose pyrimethamine treatment in patients with late onset Tay Sachs: an open lab el, extended pilot study. Orphanet J Rare Dis. 2015;10:45. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404274/

Hall P, Minnich S, Teigen C, Raymond K. Diagnosing lysosomal storage disorders: the GM2 gangliosidoses. Curr Protoc Hum Genet. 2014;83:17.161-8. https://www.ncbi.nlm.nih.gov/pubmed/25271840

Smith NJ, Winstone AM, Stellitano L, Cox TM, Verity CM. GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed. Dev Med Child Neurol. 2012;54:176-182. https://www.ncbi.nlm.nih.gov/pubmed/22115551

Osher E, Fattal-Valevski A, Sagie L, et al. Pyrimethamine increases Beta-hexosaminidase A activity in patients with late onset Tay Sachs. Mol Genet Metab. 2011;102:356-363. https://www.ncbi.nlm.nih.gov/pubmed/21185210

Bley AE, Giannikopoulos OA, Hayden D, et al. Natural history of infantile G(M2) gangliosidosis. Pediatrics. 2011;128:e1233-1241. https://www.ncbi.nlm.nih.gov/pubmed/22025593

Clarke JT, Mahuran DJ, Sathe S, et al. An open-label phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants). Mol Genet Metab. 2011;102:6-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019177/

Schneider A, Nakagawa S, Keep R, et al. Population-based Tay-Sachs screening among Ashkenazi Jewish young adults in the 21st century: hexosaminidase A enzyme assay is essential for accurate testing. Am J Med Genet A. 2009;149A:2444-2447. https://www.ncbi.nlm.nih.gov/pubmed/19876898

Shapiro BE, Pastores GM, Gianutsos J, Luzy C, Kolodny Eh. Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment. Genet Med. 2009;11:425-533. https://www.ncbi.nlm.nih.gov/pubmed/19346952

Shapiro BE, Logigian EL, Kolodny EH, Pastores GM. Late-onset Tay-Sachs disease: the spectrum of peripheral neuropathy in 30 affected patients. Muscle Nerve. 2008;38:1012-1015. https://www.ncbi.nlm.nih.gov/pubmed/18642377

Maegawa GH, Stockley T, Tropak M, et al. The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported. Pediatrics. 2006;118:el550-562. https://www.ncbi.nlm.nih.gov/pubmed/17015493

Bach G, Tomczak J, Risch N, Ekstein J. Tay-Sachs screening in the Jewish Ashkenazi population: DNA testing is the preferred procedure. Am J Med Genet. 2001;99:70-75. https://www.ncbi.nlm.nih.gov/pubmed/11170098

Hill LW, Schorr SJ. Prenatal screening for Tay-Sachs disease by Louisiana obstetricians: a survey study. South Med J. 2001;94:910-12. https://www.ncbi.nlm.nih.gov/pubmed/11592753

Guidotti JE, Mignon A, Haase G, et al. Adenoviral gene therapy of the Tay-Sachs disease in hexosaminidase A-deficient knock-out mice. Hum Mol Genet. 1999;8:831-38. https://www.ncbi.nlm.nih.gov/pubmed/10196372

Platt FM, Butters TD. New therapeutic prospects for the glycosphingolipid lysosomal storage diseases. Biochem Pharmacol. 1998;56:421-30. https://www.ncbi.nlm.nih.gov/pubmed/9763217

De Gasperi R, Gama Sosa A, Battistini S, et al. Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr– >His) in the Hex A alpha-chain gene. Neurology. 1996;47:547-52. http://www.neurology.org/content/47/2/547.short

Nakai H, Byers MG, Nowak SJ, Shows TB. Assignment of beta-hexosaminidase A alpha-subunit to human chromosomal region 15q23 – q24. Cytogenet Cell Genet. 1991;56:164. https://www.ncbi.nlm.nih.gov/pubmed/1829032

Navon R, Kolodny EH, Mitsumoto H, Thomas GH, Proia RL. Ashkenazi-Jewish and non-Jewish adult GM2 gangliosidosis patients share a common genetic defect. Am J Med Genet. 1990;46:817-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1683663/

Navon R, Proia RL. The mutations in Ashkenazi Jews with adult GM2 gangliosidosis, the adult form of Tay-Sachs disease. Science. 1989;243:1471-74. https://www.ncbi.nlm.nih.gov/pubmed/2522679

INTERNET
Kaback MM, Desnick RJ. Hexosaminidase A Deficiency. 1999 Mar 11 [Updated 2011 Aug 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1218/ Accessed: January 16, 2017

Tay-Sachs Disease. Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number:272800; Updated: 10/17/2016. Available at: http://omim.org/entry/272800 Accessed: January 16, 2017

Tay-Sachs Disease. Genetics Home Reference website. Reviewed October 2012. Available at: https://ghr.nlm.nih.gov/condition/tay-sachs-disease Accessed: January 16, 2017

Years Published

1984, 1985, 1986, 1987, 1988, 1989, 1992, 1997, 1998, 1999, 2000, 2001, 2002, 2017

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