Tay-Sachs Disease

Also known as GM2 gangliosidosis / hexosaminidase A (HEXA) deficiency

Tay-Sachs disease (TSD) is a rare autosomal recessive disorder. Classic infantile TSD causes a progressive deterioration of the nervous system beginning at approximately 3-6 months of age and usually resulting in death by the age of 4-5 years. 


  • Classic infantile TSD is typically first noticed in infants at around 4-6 months of age, before this development appears normal.
  • Affected infants show progressive weakness, loss of motor skills, decreased attentiveness and increased startle response.
  • Progressive evidence of neurodegeneration including seizures, blindness, spasticity and eventual total incapacitation follows.
  • Fundoscopy shows a grey-white area around the retinal fovea centralis, due to lipid-laden ganglion cells, leaving a central ‘cherry-red’ spot.

Other forms of TSD are very rare.

  • The juvenile (subacute), chronic, and adult-onset variants of Hex-A deficiency have later onsets, slower progression, and more variable neurological findings.
  • These include: progressive dystonia, spinocerebellar degeneration, motor neuron disease, and, in some cases of adult-onset disease, a bipolar form of psychosis.
  • The later-onset forms can also present in a similar way to an MS-type illness.

Please click on the titles to open and close the following information sections.

  • Tay-Sachs disease is caused by genetic mutations in the HEXA gene on chromosome 15.
  • These mutations result in the absence of, or deficiency in, the alpha subunit of an enzyme called Hexosaminidase-A (Hex-A) which is located in lysosomes and breaks down a fatty substance.
  • GM2 ganglioside.
  • Insufficient Hex-A levels results in an accumulation of GM2 ganglioside (cell membrane components) in the neurons of the central nervous system and retina causing progressive neurodegeneration and developmental delay.
  • Ashkenazi Jews (AJ) have a TSD carrier frequency of approximately 1:27 whereas the carrier frequency in the general population is 1:250.
  • Jews of Moroccan and Iraqi descent also have an increased risk of TSD relative to the general population, though the risk is less and the mutations differ from those in AJ.
  • The most prevalent mutations in the AJ population lead to the classic infantile form of the disease.
  • Other isolated populations with increased risk of TSD include: French Canadians of southeastern Quebec (who have a similar carrier frequency to AJ); Cajuns of southern Louisiana carry; and the Old Order Amish community in Pennsylvania.

Gene Specific:

  • Clinical diagnosis can be confirmed by carrying out an assay of Hex-A enzyme activity. Deficient Hex-A activity in serum, white blood cells or tissue cultures, including amniocytes; in the presence of normal or elevated activity of the beta-hexosaminidase B (HEX B) isoenzyme is diagnostic of TSD.
  • Other supporting evidence includes:
    • CT or MRI to detect abnormal brain storage.

Gene specific:

  • Abnormal results from an enzyme assay are often followed by DNA analysis to identify specific mutations for carrier testing of family members.
  • Numerous mutations have been identified that are associated with TSD, however, 3 mutations account for approximately 97% of all Ashkenazi Jewish carriers.
  • At least 5 other mutations, not found in AJ, occur in Moroccan Jews.

There is currently no effective treatment for Tay-Sachs disease. Management is symptomatic and supportive including:

  • antiepileptic drugs for seizures.
  • physiotherapy for spasticity.
  • speech and feeding therapists may offer support for airway protection and feeding.

Research is in process to develop an enzyme replacement therapy, however, this is yet to offer an effective treatment option at this time.

Family members should be offered genetic counselling and testing. Carrier testing and pre-natal testing is available for this condition.

  • Tay-Sachs disease is a progressive neurodegenerative disorder.
  • The classic infantile form is usually fatal by age 4-5 years.
  • Death usually occurs due to intercurrent infection.
  • In the late infantile and juvenile form, death usually occurs by age 10-15 years; often preceded by several years of vegetative state with decerebrate rigidity. Death is usually due to infection.
  • Patients with the adult form of TSD usually have a normal life expectancy, despite their neurological and psychological.
  • For children exhibiting features of TSD, initial referral would be to a paediatrician. For Jewish patients, it is important to note the child’s ancestry and higher prevalence of TSD in the Jewish population.
  • For patients that have received a TSD diagnosis the effect is devastating. On-going management is usually under the care of paediatricians plus other appropriate specialists including paediatric neurologists and community paediatricians according to how the condition presents in each affected patient.
  • Families would benefit from referral to a clinical genetics department to explore carrier status in other family members as appropriate.
  • Given the high carrier frequency, irrespective of family history, Jewish adults can be referred for TSD carrier screening carried out by Guy’s Hospital (see section below for details). This is recommended for anyone with at least one Ashkenazi Jewish grandparent prenatally.
The Cure & Action For Tay-Sachs (CATS) Foundation

The CATS Foundation, established in July 2011, aims to provide support to families affected by Tay-Sachs and to undertake fund raising activities so that research into the disease can continue. With very close ties to the leading research team into Tay-Sachs, The CATS Foundation is fully committed to ensuring that a potential treatment can be found for this devastating disease.
Tel: 07766 745904
Email: dan@cats-foundation.org

National Tay-Sachs And Allied Disease Association (USA)

The NTSAD’s mission is to lead the fight to treat and cure Tay-Sachs, Canavan and related genetic diseases and to support affected families and individuals in leading fuller lives. The site provides educational materials, information on the latest research, and many other resources for those affected by Tay-Sachs disease.

Tay-Sachs Facebook Group

A closed Facebook Group for Tay-Sachs.

Barnet General Hospital

The Department of Chemical Pathology offers a screening service on Thursday mornings. The service is by appointment only and participants will need to be referred via their GP to genetics for the Tay Sachs test. Participants will only be able to book to give a blood sample once they have seen a genetic counsellor.

Tel: 020 8375 1471
Barnet General Hospital, Department of Chemical Pathology, Wellhouse Lane, Herts EN5 3DJ

GeneReviews: www.ncbi.nlm.nih.gov/books/NBK1218

OMIM: #272800

Written by: Dr Jacky Megitt, JGD UK researcher.
Revised by: Dr Ian Ellis, Consultant Clinical Geneticist, Alder Hey Children’s Hospital
Last review: 12.07.2018

Log out