Rare Immunology News

Disease Profile

Sandhoff disease

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.


US Estimated

Europe Estimated

Age of onset





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


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.


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.


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


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.


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.


Not applicable


Other names (AKA)

Beta-hexosaminidase-beta-subunit deficiency; GM2 gangliosidosis, type 2; Total hexosaminidase deficiency;


Eye diseases; Nervous System Diseases; RDCRN


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]


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]

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:
80%-99% of people have these symptoms
Abnormality of glycosphingolipid metabolism
Abnormality of movement
Movement disorder
Unusual movement

[ more ]

Cherry red spot of the macula
Failure to thrive
Faltering weight
Weight faltering

[ more ]

Hearing impairment
Hearing defect

[ more ]

Hunched back
Round back

[ more ]

Increased size of skull
Large head
Large head circumference

[ more ]

Motor deterioration
Progressive degeneration of movement
Progressive psychomotor deterioration
30%-79% of people have these symptoms
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

Enlarged liver
Muscle weakness
Muscular weakness
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

Increased spleen size
5%-29% of people have these symptoms
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

Skeletal dysplasia
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
Enlarged heart
Increased heart size

[ more ]

Chronic diarrhea
Coarse facial features
Coarse facial appearance
Difficulty articulating speech
Episodic abdominal pain
Muscle twitch
Enlarged liver and spleen
Excessive sweating
Increased sweating
Profuse sweating
Sweating profusely
Sweating, increased

[ more ]

Increased reflexes
Decreased ability to sweat
Decreased sweating
Sweating, decreased

[ more ]

Impaired thermal sensitivity
Difficulty getting a full erection
Difficulty getting an erection

[ more ]

Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

Orthostatic hypotension
Decrease in blood pressure upon standing up
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

Upper motor neuron dysfunction
Urinary incontinence
Loss of bladder control


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]


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]

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.


    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

        • 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.


          1. Sandhoff disease. Genetics Home Reference (GHR). 2008; https://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; https://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. https://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. https://www.mayomedicallaboratories.com/test-catalog/Overview/8775.
          6. Genetic Counseling. National Tay-Sachs & Allied Diseases. https://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; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=796. Accessed 10/19/2011.

          Rare Immunology News