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Sandhoff Disease
Monday, 06 September 2004
Monday, 06 September 2004
GM2 Gangliosidosis Type II, Hexosaminidase Deficiency


Sandhoff disease is a rare, genetic disease. In this disease, there is a defect in a cellular enzyme that normally helps break down certain fatty products (called sphingolipids). Since the enzyme is defective, these fatty products don’t get broken down and start building up in the body instead. This is very damaging to cells in the body, especially in the brain. There are different types of Sandhoff disease, depending on the age in which the signs and symptoms start occurring. These types are called infantile-onset, juvenile-onset, and adult onset. The information here focuses on the infantile-onset type which starts during early infancy.


Sandhoff disease occurs in about one in 300,000 live births in the US. The prevalence varies in other countries. Sandhoff disease is medically similar to Tay-Sachs disease, another disease involving a defective cellular enzyme, which frequently occurs in individuals with an Ashkenazi Jewish heritage. However, Sandhoff disease has a higher incidence rate in non-Jewish populations compared to Tay-Sachs disease, and occurs in many different ethnic groups. Sandhoff disease occurs in both males and females.

Signs and Symptoms

Around the age of 4 to 6 months, infants may start to regress in their development and to show other signs and symptoms of Sandhoff disease as listed below: • increasing mental and motor deterioration. The infant begins to decrease alertness and interest in surroundings and loses previously attained movement skills.

  • motor weakness. The infant’s muscles may become weak and movements may be difficult
  • seizures: convulsions of the body
  • myoclonus: shock-like contractions of the muscles
  • startled reactions to sound
  • difficulty with swallowing
  • frequent respiratory infections
  • macrocephaly: the head size may be increased
  • doll-like facial appearance: the amount of facial expressions may be limited
  • cherry-red spots in the back of the eyes (an eye specialist may find this when examining the eyes)
  • early blindness
  • problems with the heart, spleen, and liver

Possible Causes

Lysosomes are small sacs in our cells that contain enzymes. These enzymes help break down material in the cell. In Sandhoff disease, there is a gene abnormality that causes one of these lysosomal enzymes to be defective. The name of the defective enzyme is called hexosaminidase. Hexosaminidase normally helps break down a type of fatty product called sphingolipids. Since hexosaminidase is defective in Sandhoff disease, the sphingolipids are not broken down properly and start building up in the cells, especially in cells of the brain. Buildup of these lipids is toxic to cells in the body and can cause cellular dysfunction. As cells get unhealthy and degenerated, the signs and symptoms of Sandhoff disease start showing. Sandhoff disease is an autosomal recessive genetic disease. This means that affected individuals have two defective copies of the hexosaminidase gene, one inherited from each parent. The parents both have one normal copy and one defective copy, so they are not affected. The parents should know that their affected children just happened to receive two defective copies by random chance, and it is not their fault in any way.


Sandhoff disease is diagnosed based on the signs and symptoms it causes and based on lab tests. Symptoms such as muscle weakness and developmental problems can be caused by different neurological and muscle diseases, so the lab tests help doctors figure out which disease is causing the symptoms. Since the hexosaminidase enzyme is defective in Sandhoff disease, there is a special blood test that measures how the hexosaminidase enzyme is working. The results of this blood test help distinguish Sandhoff disease from other genetic diseases of cellular metabolism like Tay-Sachs disease.


Currently there is no cure for Sandhoff disease, and the treatment is mostly supportive treatment for the child. This may include medications to decrease seizures and muscle contractions (myoclonus), medications to treat respiratory infections, and a special diet for feeding difficulties.


Unfortunately, a cure for Sandhoff disease has not yet been found, and children with the infantile-type of this disease have survived in the past to about 3 to 5 years of age. However, there are many studies of Sandhoff disease that are being done. Researchers are trying to find medications to stop the fatty products from building up in the cells, especially those in the brain. They are also trying to find medications to prevent the fatty products from being made in the first place. Other newer studies are focusing on decreasing inflammation in the brain to try to increase the number of healthy brain cells. Hopefully, helpful medications will be found through these studies.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


National Tay-Sachs and Allied Diseases Association (NTSAD)
This website provides support, resources, and information for families affected with Tay-Sachs and Sandhoff disease, and other similar diseases.

Lysosomal Diseases Support Group
This group is based in New Zealand, but their website has a listing of international support groups for lysosomal storage disorders, such as Sandhoff and Tay-Sachs disease.

Sandhoff Friends
This website was originally started by a family affected with Tay-Sachs disease, and includes links to families with Sandhoff disease. You may be able to contact these families for more information & resources, or simply to share your stories.

National Institute on Neurological Disorders and Stroke (NINDS)
This website provides a short summary on Sandhoff disease.

Google Search for Sandhoff Disease

References and Sources

Online Mendelian Inheritance in Man E-Medicine Disease Database Sandhoff Disease Clinical Resources (This website contains a list of links which have information on Sandhoff disease)