Tay-Sachs Disease

Tay-Sachs Disease

Tay-Sachs Disease (TSD) is a severe, progressive neurological disorder.  At birth babies appear normal with the first symptoms appearing around 4-6 months of age.  Affected infants experience the loss of early motor skills, becoming limp and unable to sit up, in addition to experiencing fits which become more frequent as the condition progresses.  These infants also have increasing feeding difficulties and are prone to inhalation and aspiration pneumonia.  Infants affected by Tay-Sachs eventually become paralysed and blind, rarely surviving past the age of 4 years.  Later onset forms of TSD occur in adolescence and adults, but these cases are rare and may be wrongly diagnosed as motor neurone disease, ataxia, multiple sclerosis 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 recessive 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 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.
  • Develop seizures (epileptic fits)
  • Progressive loss of motor skills and eventual paralysis
  • Progressive loss of sight, hearing and ability to swallow


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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. This normally occurs in the lysosomes of the cell where waste products from cell metabolism are broken down. The enzyme deficiency leads to the abnormal build up of large amounts of GM2 ganglioside.  This disturbs the function of nerve cells eventually causing them to degenerate. 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 treatment in the future but is unlikely to be available for some years. Supportive and palliative care, including tube feeding and physiotherapy are key parts 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 4 years of age.

Even today with extensive medical intervention and supportive care, most children affected by the classical infantile form of TSD 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:

image

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.

Email: info@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

Barnet General Hospital offer carrier testing on a Thursday mornings between 9am and 10am. 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.

In addition, wherever you live in the UK, you can ask your GP to refer you to your Regional Genetics Service to arrange screening for Tay Sachs.

 

Tel: 020 8375 1471
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: 12.07.2018