National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Sandhoff disease



Other Names:
Beta-hexosaminidase-beta-subunit deficiency; GM2 gangliosidosis, type 2; Total hexosaminidase deficiency; Beta-hexosaminidase-beta-subunit deficiency; GM2 gangliosidosis, type 2; Total hexosaminidase deficiency; Hexosaminidase A and B deficiency Disease; Sandhoff-Jatzkewitz-Pilz disease See More
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This disease is grouped under:

Sandhoff disease is an inherited lipid storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord.[1][2] The most common and severe form of Sandhoff disease becomes apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months when their development slows and muscles used for movement weaken. Other forms of Sandhoff disease have been described where much milder signs and symptoms begin in childhood, adolescence, or adulthood. These forms are very rare. Sandhoff disease is caused by mutations in the HEXB gene.[1] These mutations cause a deficiency of the enzyme beta-hexosaminidase, which results in the accumulation of certain fats (lipids) in the brain and other organs of the body.[2] Sandhoff disease is inherited in an autosomal recessive manner.[1] 
Last updated: 10/19/2011

Infants with the classic form of Sandhoff disease typically appear normal until the age of 3 to 6 months when their development slows and muscles used for movement weaken. Affected infants typically lose motor skills such as turning over, sitting, and crawling. They may also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Sandhoff disease may experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified through an eye examination, is characteristic of this disorder. Some affected children also have an enlarged liver and spleen, frequent respiratory infections, or bone abnormalities.[1][2] Children with the severe infantile form of Sandhoff disease usually live only into early childhood.[1]

Forms of Sandhoff disease where the symptoms develop after infancy are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease.[1]

Last updated: 2/2/2011

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of glycosphingolipid metabolism 0004343
Abnormality of movement
Movement disorder
Unusual movement
[ more ]
0100022
Ataxia 0001251
Blindness 0000618
Cherry red spot of the macula 0010729
Failure to thrive
Faltering weight
Weight faltering
[ more ]
0001508
Hearing impairment
Deafness
Hearing defect
[ more ]
0000365
Kyphosis
Hunched back
Round back
[ more ]
0002808
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ]
0000256
Motor deterioration
Progressive degeneration of movement
0002333
Progressive psychomotor deterioration 0007272
Seizure 0001250
30%-79% of people have these symptoms
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks
[ more ]
0000293
Hepatomegaly
Enlarged liver
0002240
Muscle weakness
Muscular weakness
0001324
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ]
0002205
Splenomegaly
Increased spleen size
0001744
5%-29% of people have these symptoms
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure
[ more ]
0001635
Skeletal dysplasia 0002652
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Cardiomegaly
Enlarged heart
Increased heart size
[ more ]
0001640
Chronic diarrhea 0002028
Coarse facial features
Coarse facial appearance
0000280
Dysarthria
Difficulty articulating speech
0001260
Episodic abdominal pain 0002574
Fasciculations
Muscle twitch
0002380
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased
[ more ]
0000975
Hyperreflexia
Increased reflexes
0001347
Hypohidrosis
Decreased ability to sweat
Decreased sweating
Sweating, decreased
[ more ]
0000966
Impaired thermal sensitivity 0006901
Impotence
Difficulty getting a full erection
Difficulty getting an erection
[ more ]
0000802
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ]
0000158
Orthostatic hypotension
Decrease in blood pressure upon standing up
0001278
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ]
0003202
Upper motor neuron dysfunction 0002493
Urinary incontinence
Loss of bladder control
0000020
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Last updated: 7/1/2020

Sandhoff disease is caused by mutations in the HEXB gene. The HEXB gene provides instructions for making a protein that is part of two critical enzymes in the nervous system, beta-hexosaminidase A and beta-hexosaminidase B. These enzymes are located in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, these enzymes break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A helps break down a fatty substance called GM2 ganglioside.[1]

Mutations in the HEXB gene disrupt the activity of beta-hexosaminidase A and beta-hexosaminidase B, which prevents these enzymes from breaking down GM2 ganglioside and other molecules. As a result, these compounds can accumulate to toxic levels, particularly in neurons of the brain and spinal cord. A buildup of GM2 ganglioside leads to the progressive destruction of these neurons, which causes many of the signs and symptoms of Sandhoff disease.[1]

Last updated: 2/2/2011

Sandhoff disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.[1] 
Last updated: 8/22/2011

Carrier testing is performed to identify individuals who have a gene mutation and may be at risk for having a child or other family members with the same mutation. Carriers usually do not have symptoms related to the gene mutation. Carrier testing is typically offered to individuals who have family members with a genetic condition, family members of an identified carrier, and individuals in ethnic or racial groups known to have a higher carrier rate for a particular condition.[3]

There two types of carrier screening tests: DNA and biochemical. Sandhoff carrier screening is available through DNA or biochemical testing. DNA carrier screening detects specific known mutations that are ‘looked’ for in the test. A negative DNA carrier result does not eliminate an individual's chances of being a carrier because of the possibility of carrying an unknown mutation or one not ‘looked’ for in the test. Biochemical testing, also called an enzyme assay, detects the level of the enzyme(s) in question in the blood. Enzyme assays can be done using serum or leukocytes (white blood cells). Serum is typically the standard test, but leukocyte testing is recommended when the person being tested is pregnant, on birth control pills or taking any medications that affect hormones because all of these situations can potentially interfere with the accuracy of the serum test. DNA carrier screening may be recommended if the results of the biochemical test are uncertain.[4]

Sandhoff disease is associated with deficiencies of both hexosaminidase A (hex A) and hexosaminidase B (hex B) enzyme activity. Carriers of Sandhoff disease have reduced (but adequate) amounts of both hex A and hex B. While most hex A assays are performed to identify Tay-Sachs carriers, the test also can also identify individuals that are carriers of Sandhoff disease. Looking at the total hexosaminidase activity in combination with the percent of hex A activity present can aid in determining whether an individual is a carrier of Sandhoff disease. Typically, a decreased amount of total hexosaminidase activity along with an increase in the proportion of hex A activity in leukocytes is suggestive of a Sandhoff carrier.[5] In contrast, Tay-Sachs carriers have a decrease in the amount of hex A activity. When the hex A enzyme result indicates that an individual is a possible Sandhoff carrier, the next step is typically to offer carrier testing to the individual's partner. If the partner is negative, the risk for the couple to have a child affected with the disorder is very significantly decreased. If the partner is also a possible carrier, more comprehensive testing may be offered.

We are unable to make recommendations about genetic screening and/or testing, but we do recommend genetic counseling for questions about carrier and prenatal genetic screening. Genetic counselors are non-directive healthcare professionals that help individuals understand their options. Genetic counselors are very knowledgable about testing guidelines and procedures. They can help a person to understand the tests and what the results mean for individuals, partners, children and extended family members.[6]
Last updated: 8/22/2011

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.

There is no specific treatment or cure for Sandhoff disease. Management is symptomatic and supportive. Supportive treatment includes proper nutrition and hydration and keeping the airway open. Anticonvulsants may be used to control seizures.[2] There are current research efforts underway, including experimental gene therapy, substrate reduction therapy, bone marrow transplants, and stem cell therapy.[7][8] Additional information about these investigational treatments for Sandhoff disease can be accessed through the National Tay-Sachs & Allied Diseases Association website.
Last updated: 7/30/2017

The prognosis for individuals with Sandhoff disease is poor. Death usually occurs by age 3 or 4 and is often caused by respiratory infections.[2][9]
Last updated: 10/19/2011

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources


Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Sandhoff disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • The Lysosomal Disease Network is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Lysosomal Disease Network has a registry for patients who wish to be contacted about clinical research opportunities.

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


Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources


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

  • 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 Sandhoff disease. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.


  1. Sandhoff disease. Genetics Home Reference (GHR). 2008; http://ghr.nlm.nih.gov/condition/sandhoff-disease. Accessed 10/19/2011.
  2. NINDS Sandhoff Disease Information Page. National Institute of Neurological Disorders and Stroke (NINDS). https://www.ninds.nih.gov/Disorders/All-Disorders/Sandhoff-Disease-Information-Page.
  3. Uses of Genetic Testing. GeneTests. March 19, 2004; http://www.ncbi.nlm.nih.gov/projects/GeneTests/static/concepts/primer/primerusesof.shtml#carrier. Accessed 8/22/2011.
  4. Types of Screening. National Tay-Sachs & Allied Diseases. http://www.ntsad.org/index.php/carrier-screening/types-of-screening. Accessed 8/22/2011.
  5. Hexosaminidase A and Total Hexosaminidase, Leukocytes. Mayo Clinic-Mayo Medical Laboratories. http://www.mayomedicallaboratories.com/test-catalog/Overview/8775.
  6. Genetic Counseling. National Tay-Sachs & Allied Diseases. http://www.ntsad.org/index.php/family-planning/genetic-counseling. Accessed 8/22/2011.
  7. Sandhoff Disease. National Tay-Sachs & Allied Diseases Association. October 19, 2016; https://www.ntsad.org/index.php/the-diseases/sandhoff.
  8. Sandhoff Research. National Tay-Sachs & Allied Diseases Association. October 19, 2016; https://www.ntsad.org/index.php/research-for-families/research-by-disease/sandhoff.
  9. Baumann N, Turpin JC. Sandhoff disease. Orphanet. 2006; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=796. Accessed 10/19/2011.