Sandhoff disease is a genetic, neurodegenerative condition in which individuals do not produce enough beta-hexosaminidase A (HexA) and beta-hexosaminidase B (HexB) enzymes. These enzymes are responsible for breaking down lipids/fatty substances called GM2 gangliosides in nerve cells(neurons) ^1-5 This results in excessive build-up of GM2 gangliosides, causing neuronal death and progressive damage to the brain, spinal cord and retina.

Sandhoff disease is caused by genetic changes in the HEXB gene which produces the beta-subunit of the HexA and HexB enzymes.^1-5 The less HexA and HexB a person has, the more severe the disease and the earlier the symptoms begin to appear.^2,3 Sandhoff disease can be categorised into different forms depending on the age of onset:^1-4

• Infantile form – begins between 3 to 6 months old (most common and severe form)
• Juvenile form – begins between 2 to 10 years old
• Adult or late-onset form – begins in late teenage or early adulthood

Sandhoff disease is a type of lysosomal storage disorders called GM2 gangliosidoses. Other types of GM2 gangliosidoses include Tay-Sachs disease and GM2 gangliosidoses AB variant, which are also caused by accumulation of GM2 gangliosides in the nervous system but are due to genetic changes in different genes.^1,3

Synonyms: Type 2 GM2 gangliosidosis, GM2-Gangliosidosis type II, hexosaminidases A and B deficiency, GM2 gangliosidosis variant 0, beta-hexosaminidase-beta-subunit deficiency total hexosaminidase deficiency, Sandhoff-Jatzkewitz-Pilz disease.^1-4

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:796 Sandhoff disease

ICD-11: 5C56.00 Gangliosidosis

The symptoms and severity of Sandhoff disease vary between individuals depending on the level of HexA and HexB deficiency.^2,3 Symptoms often worsen over time due to progressive central nervous system damage.

Infantile Sandhoff disease – Infants often appear normal at birth, and symptoms begin to appear between 3 and 6 months old.² Symptoms include decreased attentiveness, poor ability to fix and follow moving objects with their eyes, exaggerated startle response, seizures, and low muscle tone.^1-5 A characteristic sign of infantile GM2 gangliosidoses is a cherry-red spot on the retina, which is often observed during eye exam.^1,2 Infants progressively become less responsive, lose their vision, have trouble swallowing, and develop an enlarged head, kidneys and spleen.² Infants are prone to respiratory infections and related life-threatening complications. They may eventually become unconscious due to severe brain damage.^1,2

Juvenile Sandhoff disease – Children often develop normally and symptoms begin to appear around 2 years old. Their movement and speech development stop improving, and they may lose previously acquired skills.² Symptoms begin to appear such as poor coordination and balance, muscle spasms, stiffness, seizures, difficulty speaking, and cognitive decline.^1,2 They may eventually become unconscious due to severe brain damage, and may be at risk of life-threatening aspiration (when food, saliva, or liquid enters the airway, instead of being swallowed).²

Adult Sandhoff disease progresses more slowly than infantile or juvenile Sandhoff disease.² Symptoms may include: ^1-5

• lower limb weakness causing difficulty climbing stairs
• poor muscle control leading to incoordination, unsteady walking, slurred speech, abnormal eye movements, difficulty swallowing
• tingling, numbness, or unusual sensations in the hands or feet
• dysautonomia, which is when the body’s autonomic nervous system (that controls involuntary functions such as breathing, heart rate, and blood pressure) does not work properly
• psychiatric symptoms such as depression or anxiety
• progressively lose the ability to walk with high risk of falls

Please speak to your medical team to learn more about the symptoms and complications of Sandhoff disease.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Sandhoff disease is a genetic condition. It is caused by disease-causing genetic changes (variants) in the HEXB genes on chromosome 5.¹ The HEXB gene produces the beta-subunit of hexosaminidase A (HexA) and hexosaminidase B (HexB) enzymes that breaks down GM2 gangliosides.^2-4 The genetic variants in HEXB gene results in the deficiency of HexA and HexB enzymes in the body. GM2 gangliosides builds up in neurons, causing neuron degeneration, and damages the brain and nervous system.^1,5

All individuals have two copies (alleles) of the HEXB gene – one on each chromosome that is inherited from each parent. Sandhoff disease is an autosomal recessive condition, which means both copies of the HEXB gene must have the disease-causing genetic variants.^2,4 The genetic variant can be inherited, which means it can be passed on to the next generation. Individuals with the genetic variant in only one copy are usually unaffected, but will be a carrier and may pass on that variant to their children.⁴ If both parents are carriers (each have a copy of the disease-causing variant), there is a 25% chance the child will inherit both disease-causing variants and have Sandhoff disease. More information on autosomal recessive inheritance pattern can be found at Centre for Genetics Education: Autosomal recessive inheritance.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of Sandhoff disease may be made based on:^1,2,5

• physical examination
• enzymatic test showing abnormally low or absent HexA and HexB activity
• neuroimaging of the brain (MRI or CT scans)
• neurological tests to check the function of the brain and nervous system
• genetic tests to look for disease-causing genetic variants in the HEXB gene

As part of the diagnostic process, doctors may do a differential diagnosis, where they rule out other conditions that have similar symptoms, such as Tay-Sachs disease, GM2 gangliosidosis AB variant, Gaucher disease, Canavan disease, infantile Alexanders disease, Niemann-Pick disease, Batten disease, Leigh syndrome and others.^3,4

Please speak to your medical team to learn more about the available diagnostic pathways for Sandhoff disease.

There is currently no curative treatment for Sandhoff disease. Treatment is targeted at managing symptoms and improving quality of life. This may include:^1,4

• management of seizures
• nutritional support including use of feeding tube
• airway management such as use of vibrating vests to clear airways
• mobility assistance
• physiotherapy
• occupational therapy
• speech therapy and use of augmentative and alternative communication tools
• management of psychiatric symptoms

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities. For many rare diseases, treatment options may be limited. Participation in a clinical trial may provide access to new or emerging therapies.

Healthcare professionals involved in the care of people with Sandhoff disease may include general practitioners (GP), paediatriciains, metabolic specialists, neurologists, ophthalmologists, gastroenterologists, nutritionists, physiotherapists, occupational therapists, speech pathologists, psychologists, dietitians, audiologists, genetic counsellors and others.² The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

This may not be applicable to all rare diseases but for many, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

We are not aware of any clinical care guidelines for Sandhoff disease in Australia or internationally. If you know of any relevant care guidelines, please let us know via the Contribute page.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

Australian Organisation:
Rare Find Foundation
Website: https://www.rarefindfoundation.org/
Rare Find Foundation aims to support those affected and their families, supporting research and raising awareness of Tay-Sachs and Sandhoff diseases.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Sandhoff disease varies between individuals, and each person’s experience is unique.

Rare Find Foundation: Our families has personal stories of people living with Sandhoff disease.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

Rare Find Foundation: Information for families has information for families and carers supporting those diagnosed with Tay-Sachs and Sandhoff diseases.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on Sandhoff disease can be found at:

• Rare Find Foundation: Sandhoff Disease
• National Organization for Rare Disorders (NORD): Sandhoff disease
• Genetic and Rare Diseases (GARD) Information Center: Sandhoff disease

GeneReviews®: Sandhoff Disease

Online Mendelian Inheritance in Man, OMIM^®:#2668800 Sandhoff disease

Orphanet: Sandhoff disease

Human Phenotype Ontology (HPO): Sandhoff disease

Inborn Errors of Metabolism Knowledgebase (IEMbase): #IEM number: IEM0837 HEXB-related Beta-hexosaminidase subunit beta deficiency

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.