Tay-Sachs disease is a genetic, neurodegenerative condition in which individuals do not produce enough beta-hexosaminidase A (HexA) enzyme that is responsible for breaking down lipids/fatty substances called GM2 gangliosides in nerve cells (neurons).^1-4 This results in excessive build-up of GM2 ganglioside especially in the brain, spinal cord, and retina, leading to neuronal death and brain damage.^1-3

Tay-Sachs disease is caused by genetic changes in the HEXA gene which produces the HexA enzyme. The less HexA a person has, the more severe the disease and the earlier the symptoms begin to appear.² Tay-Sachs disease can be categorised into different forms depending on the age of onset:^1,3

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

Tay-Sachs disease is classified as a type of lysosomal storage disorders called GM2 gangliosidoses. Other types of GM2 gangliosidoses include Sandhoff 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

Synonyms: GM2 gangliosidosis type 1; beta-hexosaminidase subunit alpha deficiency; GM2 gangliosidosis, Tay-Sachs variant; GM2 gangliosidosis, hexosaminidase A deficiency variant; HEXA disorder; sphingolipidosis, Tay-Sachs.^3,4

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:845 Tay-Sachs disease

ICD-11: 5C56.00 Gangliosidosis

The symptoms and severity of Tay-Sachs disease vary between individuals depending on the level of HexA deficiency.¹ Symptoms often worsen over time due to progressive central nervous system damage.²

Infantile Tay-Sachs disease is the most severe form and often progresses rapidly.¹ Infants often appear normal at birth, and symptoms begin to appear around 6 months old.² Symptoms include low muscle tone (hypotonia), irritability, exaggerated startle response (responses that are greater in intensity than normal) to noise, difficulty breathing, and large head size.^1,3 A characteristic sign of infantile Tay-Sachs disease is a cherry-red spot on the retina, which is often observed during eye exam.^1,2 Infants may gradually progress to have seizures, stiffness, vision loss, loss of previously acquired skills such as crawling, rolling over, and sitting up, and paralysis.^1-4

In juvenile Tay-Sachs disease, symptoms begin to appear around 2 to 10 years old. Symptoms include muscle weakness, clumsiness, poor coordination, stiffness, muscle cramps, seizures, difficulty speaking and swallowing.^1,3 A cherry-red spot is not consistently observed, and optic nerves damage tends to progress significantly, which can affect vision. Individuals may progressively lose their ability to speak and eat on their own.^2,3

Individuals with either infantile and juvenile Tay-Sachs disease are prone to respiratory infections and related complications such as pneumonia and respiratory failure which can be life-threatening.² They may eventually become unconscious due to severe brain damage, and have shortened life expectancy.^1-3

Adult Tay-Sachs disease presents in teenage years (adolescence) or adulthood and progresses more slowly than infantile or juvenile Tay-Sachs disease.² Symptoms include unsteady walking, poor muscle control, lower limb weakness causing difficulty climbing stairs, cognitive decline, slurred speech, difficulty swallowing, and psychiatric symptoms such as psychotic depression, paranoia, hallucinations, and bipolar symptoms.^1-4 Individuals may progressively lose the ability to walk.⁴

Please speak to your medical team to learn more about the symptoms and complications of Tay-Sachs 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.

Tay-Sachs disease is a genetic condition. It is caused by disease-causing genetic changes (variants) in the HEXA genes on chromosome 15.⁴ The HEXA gene produces alpha-subunit of hexosaminidase A (HexA) enzyme, which breaks down GM2 ganglioside.⁴ The genetic variants in HEXA gene results in the deficiency of HexA enzyme in the body. GM2 ganglioside builds up in neurons, causing neuron degeneration, and damages the brain and nervous system.¹

All individuals have two copies (alleles) of the HEXA gene – one on each chromosome that is inherited from each parent. Tay-Sachs disease is an autosomal recessive condition, which means both copies of the HEXA gene must have the disease-causing genetic variants. 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.¹ 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 Tay-Sachs 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 Tay-Sachs disease may be made based on:^2-4

• physical examination
• enzymatic test showing reduced or absent HexA activity
• neuroimaging of the brain (MRI or CT scans)
• genetic tests to look for disease-causing genetic variants in the HEXA 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 GM2 gangliosidosis AB variant, Sandhoff disease, GM1 gangliosidosis, Leigh syndrome, infantile Gaucher disease, Niemann–Pick disease, galactosialidosis, Friedreich’s ataxia, neuronal ceroid lipofuscinosis, amyotrophic lateral sclerosis, spinal muscular atrophy, amyotrophic lateral sclerosis, hepatolenticular degeneration, cerebrotendinous xanthomatosis, metachromatic leukodystrophy, and X-linked adrenoleukodystrophy, and others.^2-4

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

There is currently no curative treatment for Tay-Sachs disease. Treatment is targeted at managing symptoms (symptomatic management) and improving quality of life. This may include:^1-3

• management of seizures
• management of infections to avoid life-threatening complications
• nutritional support including use of feeding tube
• mobility assistance such as walking frame, wheelchair, specialised stroller
• 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 Tay-Sachs disease may include general practitioners (GP), paediatricians, metabolic specialists, neurologists, ophthalmologists, gastroenterologists, nutritionists, physiotherapists, occupational therapists, speech pathologists, psychologists, dietitians, audiologists, genetic counsellors and others.^2,3 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 Tay-Sachs 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.

Tay-Sachs disease varies between individuals, and each person’s experience is unique.

Rare Find Foundation: Our families has personal stories of people living with Tay-Sachs 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 Tay-Sachs disease can be found at:

• healthdirect: Tay-Sachs disease
• Better Health Channel: Tay-Sachs disease
• National Organization for Rare Disorders (NORD): Tay-Sachs disease
• Genetic and Rare Diseases (GARD) Information Center: Tay-Sachs disease

StatPearls: Tay-Sachs disease

Online Mendelian Inheritance in Man, OMIM^®:#272800 Tay-Sachs disease; TSD

Orphanet: Tay-Sachs disease

Human Phenotype Ontology (HPO): Tay-Sachs disease

Inborn Errors of Metabolism Knowledgebase (IEMbase): #IEM0836 HEXA-related Beta-hexosaminidase subunit alpha 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.