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Tay-Sachs Disease

Tay-Sachs disease (TSD) is a severe neurological degenerative disease. At birth, babies appear normal with the first clear symptoms showing around 4-6 months of age when they experience rapid and progressive deterioration of their speech, motor and developmental skills. Affected infants eventually become blind, deaf and unresponsive and rarely survive past the age of 4 years. Later-onset forms of TSD occur in adolescents and adults but these cases are very unusual – and may be wrongly diagnosed as motor neurone disease, ataxia or another neurological condition.

If you have just received a diagnosis there is help and support available - please see ‘Further information and support’ below for links to valuable resources. It is also important to note that not every person with this condition experiences all the symptoms described and it is worth talking to your doctor or other relevant healthcare specialists to discuss you or your family member’s individual case.

Inheritance

Tay-Sachs disease is an autosomal recessiveRecessive disorders require both parents to carry a specific disorder-related mutation and pass it on to their child for the disorder to be inherited condition.

Prevalence

The carrier frequency of TSD in the Ashkenazi Jewish population is approximately 1 in 27, which is around 10 times higher than the carrier frequency in the general population.

Classical infantile TSD, as well as the later onset forms, occur with increased frequency among Ashkenazi Jews – as well as Moroccan Jews and Jews of Iraqi descent.

TSD has an increased frequency in some other communities around the world. The carrier frequency in the general population is 1in 250.

Symptoms

In classical TSD, as opposed to the later-onset forms, signs and symptoms commonly include:

  • Loss of head control and loss of ability to maintain sitting position unaided or roll over
  • Cherry red spot on the retina of the eye
  • Rigid limbs but floppy spinal muscles
  • Tendency to startle easily with sharp sounds or vibrations.
  • Progressive loss of attention and the capacity to fix visually on objects.
  • Progressive loss of motor skills and eventual paralysis
  • Progressive loss of sight, hearing and ability to swallow
  • May develop seizures (epileptic fits)
  • Dementia



Please click on the titles to open and close the following information sections
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TSD is caused by a mutation in the HEXA gene, which leads to a deficiency of an enzyme called hexosaminidase A (Hex-A). Hex-A is required to recycle a particular component called GM2 ganglioside in cells, especially nerve cells. The enzyme deficiency disturbs the function nerve cells eventually causing them to die. As a consequence, individuals with classical TSD experience progressive brain damage. TSD is part of a group of ‘lysosomal storage disorders’, in which inherited defects in enzymes or other critical components of the lysosome lead to disease.

Despite much active research, there is currently no cure or treatment to slow TSD progression. Regenerative medicine and gene therapy hold the promise of definitive treatment but is unlikely to be available for some years. Supportive and palliative care, including physiotherapy, is a key part of the management of affected children - providing relief of symptoms and discomfort. It can help prevent distressing seizures and limb contractures as well as maintaining adequate hydration and nutrition. Support for affected families and carers is a critical aspect of management and requires multidisciplinary professional teams in hospital and the community.

Classical TSD is invariably fatal in early childhood, typically by 3 to 6 years of age.

Even today with extensive medical intervention and supportive care, more than half the affected children die before their fourth birthday.

TSD is diagnosed using a biochemical test of the Hex-A level in a blood sample from a child who is exhibiting symptoms. Children with TSD have complete (or almost complete) absence of Hex-A in the blood. Subsequent DNA testing can be used to identify the mutations in the HEXA gene which have caused the deficiency.

Carrier testing can be done by measuring the Hex-A levels in blood, or by looking for mutations in the DNA.

Tay-Sachs carriers have a reduced level of Hex-A in their blood upon biochemical testing, however this reduced level does not cause health problems. Biochemical testing is the most sensitive type of carrier test and will detect 100% of carriers. In some cases, people will receive an ‘inconclusive’ result from this test because their Hex-A is on the borderline between the normal and carrier ranges. When this occurs DNA testing for mutations can be used to clarify the result, and/or a repeat biochemical test can be performed.

The diagram below illustrates various test results for different levels of Hex-A:

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Some laboratories use the biochemical carrier test, and others use the DNA mutation test. In the Ashkenazi Jewish population there are 3 mutations which are commonly found in carriers. If biochemical carrier testing is not performed, testing of these three mutations will detect approximately 97% of carriers.

Numerous other mutations have been identified and at least 5 mutations not found in the Ashkenazim occur in Moroccan Jews. The position for carrier testing and advice to couples is different for those whose partner is not of known Ashkenazi ancestry – understanding the origins of the different partners can be helpful in refining the advice regarding TSD carrier risk and testing.

Prenatal testing is available and involves specialist biochemical testing. To arrange this test, your doctor needs to co-ordinate with the local regional genetics department

For more details about testing, please refer to the testing section.

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: .(JavaScript must be enabled to view this email address)

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.

Guy’s and St Thomas’ Hospital

The Clinical Genetics Department runs a walk-in clinic for Tay-Sachs disease screening on Monday mornings (except Bank holidays) between 9.30am and 11am. The service is free and no referral or appointment is needed.

Tel: 020 7188 1364
Genetics Clinic, 7th Floor Borough Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT.

Barnet General Hospital

The Department of Chemical Pathology offers a screening service on Thursday mornings. You can book your appointment in advance at the following link

Tel: 020 8216 4394
Barnet General Hospital, Department of Chemical Pathology, Wellhouse Lane, Herts EN5 3DJ

To find out more about general resources relevant to Jewish genetic disorders, please visit our resources and support section.

 

Written by Jnetics.
Approved by Dr Ian Ellis, Consultant Clinical Geneticist, Alder Hey Children’s Hospital
Last review: 1.2.2015