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Disease Profile

Tay-Sachs disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

E75.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

GM2 gangliosidosis, type 1; HexA deficiency; B variant GM2 gangliosidosis;

Categories

Eye diseases; Metabolic disorders; Nervous System Diseases

Summary

Tay-Sachs disease is a rare, inherited neurodegenerative disease. People with Tay-Sachs disease do not have enough of an enzyme called beta-hexosaminidase A. The less enzyme a person has, the more severe the disease and the earlier that symptoms appear. There are 3 forms of Tay-Sachs disease, distinguished by the general age of onset:[1][2]

  • Infantile the most common severe form, with symptoms appearing in the first few months of life. Symptoms include a loss of skills learned (regression), seizures, and loss of muscle and mental functions. Children with this form do not survive past early childhood.
  • Juvenile a form with a range of severity, with symptoms appearing any time during childhood (but usually between ages 2 and 5). Symptoms include behavior problems, gradual loss of skills, frequent respiratory infections, and seizures. People with this form typically do not survive past their teenage years.
  • Late onset/adult the least severe form, with symptoms appearing in late childhood to adulthood. Symptoms may include clumsiness, muscle weakness, psychiatric disorders, and gradual loss of skills, often leading to the need for mobility assistance. Intellect and behavior become impaired in some cases. The lifespan varies from shortened to unaffected.

Tay-Sachs disease is caused by mutations in the HEXA gene and inheritance is autosomal recessive. The HEXA gene gives the body instructions to make part of the beta-hexosaminidase A enzyme, which is needed to break down a substance called GM2 ganglioside. When the enzyme is not functional or not made, GM2 ganglioside builds up in the nerve cells (neurons) of the brain and spinal cord, causing the symptoms of the disease.[3]

The diagnosis of Tay-Sachs disease involves a blood test that detects absent or very low levels of beta-hexosaminidase A enzyme activity. Molecular genetic testing of the HEXA gene may be used to identify the specific mutations present, or to rule out the disease if a false-positive blood test result is suspected.[4]

Currently there is no cure for Tay-Sachs disease, and there are no therapies that slow the progression of the disease. Treatment aims to relieve symptoms and increase quality of life. For example, children with seizures may be treated with anti-seizure medicines. Adequate nutrition and hydration are recommended, to prevent complications.[4][5]

Note: You may also find Tay-Sachs disease referred to as a lysosomal storage disease or a GM2-gangliosidosis because the disease involves a lysosomal enzyme and the buildup of GM2 ganglioside.

Symptoms

The first symptoms of Tay-Sachs disease may appear from infancy to adulthood, depending on how much beta-hexosaminidase A enzyme activity a person has (if any).

In the most common form, the infantile form, infants have no enzyme activity, or an extremely low level (less than 0.1%). They typically appear healthy in the newborn period, but develop symptoms within 3 to 6 months of age. The first symptom may be an exaggerated startle response to noise. Infants with this form begin to lose milestones such as rolling and sitting (regression) and develop muscle weakness, which gradually leads to paralysis. They also lose mental functions and become increasingly unresponsive to their surroundings. By 12 months of age, they begin to deteriorate more rapidly, developing blindness, seizures that are hard to treat, and difficulty swallowing. Infants with this form of Tay-Sachs disease typically do not survive past 4 years of age. The most common cause of death is complications from lung inflammation (bronchopneumonia).[1][2][5]

The juvenile form is less common and is characterized by having very little enzyme activity, typically less than 1% of normal activity. Depending on exactly how much activity there is, symptoms may begin any time during childhood, most commonly between ages 2 and 5. Children with this form often develop frequent infections, behavioral problems, and have more slowly progressive loss of movement control, speech, and mental function. They may also begin to have seizures and lose their vision. Children with the juvenile form often spend several years having no responsiveness or awareness before passing away in late childhood or adolescence. Infection is a common cause of death.[1][2][5]

The late onset form, sometimes called the adult or chronic form, is also less common and is characterized by having less than 10% of normal enzyme activity. Symptoms and severity vary more among people with this form. Symptoms may begin in childhood to adulthood, but the disease is often not diagnosed until adolescence or adulthood. Neurological impairment is slowly progressive and may lead to clumsiness and loss of coordination, muscle weakness, tremors, difficulty speaking or swallowing, and uncontrollable muscle spasms and movements. Many people eventually need mobility assistance. In some people with this form, the first obvious symptom is a severe psychiatric disorder such as schizophrenia. Impaired intellect or dementia may or may not develop. Some people with the late onset form have a shortened lifespan due to the disease, while others do not.[1][2][5]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Ataxia
0001251
Blindness
0000618
Cherry red spot of the macula
0010729
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
EEG abnormality
0002353
Global developmental delay
0001263
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hyperreflexia
Increased reflexes
0001347
Increased muscle lipid content
Fat accumulation in muscle fibers
Fat deposits in muscle fibers
Lipid accumulation in skeletal muscle
Skeletal muscle lipid accumulation

[ more ]

0009058
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation

[ more ]

0006887
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Psychomotor deterioration
0002361
Seizure
0001250
30%-79% of people have these symptoms
Hepatomegaly
Enlarged liver
0002240
Muscular hypotonia
Low or weak muscle tone
0001252
Myotonia
0002486
Optic atrophy
0000648
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Splenomegaly
Increased spleen size
0001744
Percent of people who have these symptoms is not available through HPO
Apathy
Lack of feeling, emotion, interest
0000741
Aspiration
0002835
Autosomal recessive inheritance
0000007
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Exaggerated startle response
0002267
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
GM2-ganglioside accumulation
0003495
Hypertonia
0001276
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Pallor
0000980
Poor head control
0002421

Cause

Tay-Sachs disease is caused by mutations in the HEXA gene. The HEXA gene provides instructions for making part of an enzyme called beta-hexosaminidase A, which plays a critical role in the brain and spinal cord. This enzyme is located in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, beta-hexosaminidase A helps break down a fatty substance called GM2 ganglioside.[3]

Mutations in the HEXA gene disrupt the activity of beta-hexosaminidase A, which prevents the enzyme from breaking down GM2 ganglioside. As a result, this substance accumulates to toxic levels, particularly in neurons in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these neurons, which causes the signs and symptoms seen in Tay-Sachs disease.[3]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Currently, there is no cure for Tay-Sachs disease, and there is no treatment that stops or slows the progression of the disease. Treatment aims to relieve some of the symptoms, manage infections, prevent complications, and increase quality of life as much as possible. Treatment for symptoms may include anticonvulsants to control seizures in children, and antipsychotic medications for psychiatric disorders in adults. Of note, tricyclic antidepressants are thought to be ineffective, and they may actually inhibit the little enzyme activity that may be present in some people with the disease. Preventing complications involves getting adequate nutrition and hydration, preventing airway obstruction, and avoiding severe constipation with food additives, stool softeners, or laxatives.[4][5] Research into potential treatments for Tay-Sachs disease is ongoing.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Tay-Sachs disease. Click on the link to view a sample search on this topic.

          References

          1. Tay-Sachs Disease. National Tay-Sachs and Allied Diseases Association. October 14, 2016; https://www.ntsad.org/the-diseases/tay-sachs.
          2. Baumann N, Turpin J. Tay-Sachs disease. Orphanet. April, 2006; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=845.
          3. Tay-Sachs disease. Genetics Home Reference (GHR). October 2012; https://ghr.nlm.nih.gov/condition/tay-sachs-disease.
          4. Kaback MM, Desnick RJ. Hexosaminidase A Deficiency. GeneReviews. August 11, 2011; https://www.ncbi.nlm.nih.gov/books/NBK1218/.
          5. Tegay DH. GM2 Gangliosidoses. Medscape Reference. December 11, 2014; https://emedicine.medscape.com/article/951943-overview.

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