Sandhoff Disease

What is Sandhoff disease? Sandhoff disease (SD) is an inherited (genetic), incurable disease. Symptoms first appear at about the age of 6 months, when an apparently healthy baby stops smiling, crawling or turning over, loses their ability to grasp or reach out, and gradually becomes blind and paralysed. There is no cure for the disease and death usually occurs at about three years of age. Babies with SD do not have the genetic information which tells his/her body to produce certain enzymes (called B-Hexosaminidase A and B-Hexosaminidase B) that are necessary for breaking down certain substances in the brain and nerve cells. These substances then accumulate in the nerve cells causing irreversible damage. Sandhoff disease is very similar to Tay-Sachs disease, but occurs more commonly in the non-Jewish community. Who gets Sandhoff disease? Genetic diseases are often more common in specific community groups. Sandhoff disease has a high incidence in the Creole population of the northern part of Argentina and an increased incidence in the Metis Indians in Canada and in the Lebanese community. What causes Sandhoff disease? SD is caused by inheriting a 'double dose' of a fault in a gene (HEXB) which codes for the HexA and HexB enzymes. Every person has two copies of this gene in each cell of their body. A person will only be affected by SD if s/he has a mutation in both copies of the HEXB gene. This can only happen if one faulty copy is inherited from each parent. One in every 26 people from the Creole population carries one copy of the faulty gene and one regular copy of the gene. In the general population, however, only about one in 300 people carry a faulty copy of the HEXB gene. Carriers themselves are not affected by the disease. How is the disease transmitted? When two unaffected carriers of the HexB gene mutation become parents, then for each pregnancy:

There is a 1-in-4 (25%) chance that the child will inherit the regular HEXB gene from each parent and will be completely free of the HEXB gene mutation and will not be affected by SD (figure A). There is a 2-in-4 (50%) chance that the child will inherit both a regular copy and a faulty copy of the HEXB gene and be a carrier of the faulty gene, unaffected by SD, just like his/her parents (figure B and C). There is a 1-in-4 (25%) chance that the child will inherit the faulty HEXB gene from each parent. This child will be affected with Sandhoff disease (figure D).

Does it affect one's health to be a carrier of the HEXB genetic mutation? No. Carriers of the HEXB gene mutation are completely unaffected by SD. Does Sandhoff disease affect only males? No. Sandhoff disease can affect both males and females. Is it possible to test to see if a person is a carrier of the faulty HEXB gene? Yes. Although there is no cure or effective treatment for SD, genetics carrier testing is available. Extensive genetics carrier testing for Tay-Sachs disease in various regions of the world has lead to its virtual elimination in these areas. Why is a person's ancestry relevant to genetics carrier testing? There are different faults (mutations) found in genes. Some faults are specific to particular ethnic groups or regions in the world. The various laboratory tests being used have each been designed to detect specific genetic faults that are most common among individuals who are of particular ancestries, origin and descent. For whom is genetics carrier testing for SD appropriate? Testing is available for all men and women over the age of 16. However, it is particularly relevant to anyone who is in a high risk category (see "Who gets Sandhoff disease", above). How is the testing performed? A small blood sample is taken and the level of the HexA and HexB enzymes is measured. This is the same enzyme test that is used for Tay-Sachs disease testing and so carriers of the HEXB gene mutation are routinely picked up when testing for Tay-Sachs disease. What confidence can I have in the test results? The testing laboratory has been accredited by the International Tay-Sachs disease Testing Quality Control and Data Collection. If I do not have a family history of Sandhoff disease do I need to be tested? Yes. Over 95% of couples with children affected by SD have no family history of the disease because the HEXB gene mutation is silently passed down through the generations. However, if there is a family history, then the risk is much greater. People who have a known family history of SD should seek further information through genetics counselling (telephone: (61) 2 9926 7324). Can any other conditions be tested for at the same time? Yes. The laboratory can test for genetic carriers of some other inherited disorders at the same time as testing for Sandhoff disease. Testing is already available for Tay-Sachs disease, cystic fibrosis, Canavan disease and Fanconi anaemia which are genetic conditions inherited in a similar way to Sandhoff disease. Over the next few years, testing will become available for other inherited conditions. You will be asked to provide written consent if you want us to test for these additional conditions in the future.

Contact: PaLMS Laboratory & Community Genetics: Ph:992-68899 Fax:9926-8484 Email:aproos@doh.health.nsw.gov.au

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