An Overview of Sandhoff Disease

Sandhoff Disease is a genetic disease that progressively destroys the nervous system. This disease comes in three forms; the classic infantile form (This form of the disease is the most severe, and children with this form usually do not live past three years of age.), the juvenile form, and the adult onset form (This form of the disease is also referred to as chronic Sandhoff.). The juvenile and adult forms of the disease are not quite as severe as the classic infantile form (Ntsad.org, 2010).

Sandhoff Disease History and Genetic Information

Sandhoff Disease was named after a German chemist named Conrad Sandhoff. He described the disease and its characteristics in Life Science in the year 1968 (Ntsad.org, 2010).

Sandhoff, which is almost a twin to Tay-Sachs Disease, is a recessive autosomal condition, which means that both parents must carry the defective gene in order for any of their offspring to inherit the disease. One type of the disease will run in a family. This means that one set of parents will not have one child with the classic infantile form and another child with another form of the disease (Ntsad.org, 2010).

What is the Cause of Sandhoff Disease?

Both Sandhoff Disease and Tay-Sachs Disease cause fatty material, also known as GM2 gangliosides, to accumulate in the brains of effected individuals. Sandhoff Disease, however, has mutations that occur on a different gene, as well as on a different chromosome. Persons with Sandhoff Disease have mutations on the beta ß subunit of the Hex-A gene on the fifth chromosome. Persons with Tay-Sachs have mutations on the alpha ß subunit of the Hex-A gene on the 15th chromosome. Because both of the alpha and the beta subunits are necessary for the functioning of Hex-A, individuals effected with Sandhoff Disease lack Hex-An activity. The B subunit, on the other hand, is also critical for the functioning of a different type of hexosaminidase that is called Hex-B. Because this is the case, individuals with Sandhoff disease are deficient in both Hex-A and Hex-B activity while individuals affected with Tay-Sachs have Hex-B activity (Ntsad.org, 2010).

It is true that Hex-A and Hex-B are different concerning the subunits that they contain; however, both of these are crucial for breaking down GM2 gangliosides. GM2 gangliosides are substances that contain fats and sugars that are primarily made inside the neurons of the brain. Individuals who are affected by Sandhoff Disease are not able to break down the GM2 gangliosides, thus they will build up in compartments of the cell known as the lysosomes. Lysosomes are the part of the cell that recycles cell waste due to the fact that lysosomes contain enzymes that break down molecules. When one of the enzymes are not functioning properly or not at all, this will cause a buildup in the waste that the enzyme is unable to break down. When the buildup begins to be too much, the cell will die. Because GM2 gangliosides are chiefly found in the neurons of the brain, failure to break down the GM2 gangliosides will result in progressive damage to the nervous system, which will eventually result in a loss of function. Because the buildup of GM2 gangliosides is the main root of Sandhoff Disease, This particular diseases classified as a GM2 gangliosidosis, which sets it apart from other diseases that affect lysosomal storage (Ntsad.org, 2010).

Just like Tay-Sachs disease, the severity of Sandhoff Disease will depend on how much of the residual enzyme a sufferer has. For instance, effected individuals with practically no hexosaminidase will have the classic infantile form of the disease. Individuals who have some levels of hexosaminidase will have the juvenile form of the disease. Individuals with higher levels of hexosaminidase that still remain below normal will have the adult onset form of the disease (Ntsad.org, 2010).

The classic infantile form of Sandhoff Disease is the most severe; yet, it is the most common. The juvenile and adult onset forms of the disease are less common, and the severity varies, depending on the sufferer and the course of progression that the disease wishes to take. The amount of enzyme present in a sufferer, as well as the course the disease wishes to take, depends on the mutations that occur in the ß subunit of Hex-A (Ntsad.org, 2010).

While both Sandhoff Disease and Tay-Sachs Disease are inherited in the same way, Sandhoff is more common in people who are not of Jewish descent. Tay-Sachs Disease, on the other hand, seems to be much more common among individuals of Jewish descent (Ntsad.org, 2010).

Treatment

Presently, there is no known treatment or cure for Sandhoff Disease. However, various tests are being run on mice in laboratories around the world, since mice are the perfect models for experimentation concerning Sandhoff Disease. Also, there are clinical trials testing the effectiveness of a new drug called miglustat in treating all three forms of the disease (Ntsad.org, 2010).

Enzyme replacement has also been explored in treating all three forms of the disease; yet, there are a number of serious obstacles that keep such a treatment from working. Since the cells that are attacked by Sandhoff Disease are protected by the blood-brain barrier, Hex-A and Hex-B enzymes are not able to reach these cells through the bloodstream. Stem cell transplants using the blood from umbilical cords has been tried on a very small group of infants and young children with Sandhoff Disease; however, there is not enough information to determine whether or not this treatment is effective. Other treatments that are being researched are neural stem cell therapy, Gene therapy, and molecular or pharmacological chaperone therapy (Ntsad.org, 2010).

Support

There are a number of organizations and programs that are designed to provide support to effected individuals and their families. The National Tay-Sachs & Allied Diseases Association, Inc. is an example of such an organization (Ntsad.org, 2010).

Testing

There are tests that can be performed to verify the existence of the mutated gene, as well as determine the diagnosis of Sandhoff Disease. Parents can receive a DNA test to see if the both of them possess the mutated gene. Tests can be done on unborn children, as well as on older children and adults with the disease to come to a diagnosis. These tests are extremely accurate and reliable because of the abnormal levels of Hex-A and Hex-B (Ntsad.org, 2010).

Sources

Ntsad.org. (2010). Sandhoff Disease. Retrieved from http://www.ntsad.org/S02/S02sandhoff.htm