Sandhoff Disease

What is Sandhoff disease?

Sandhoff disease is a rare genetic disorder that destroys nerve cells in the brain and spinal cord. It usually appears in infancy, but it can occur in children and adults.

Sandhoff disease is a lysosomal storage disorder. Almost every cell in the body contains lysosomes. Lysosomes have dozens of enzymes that break down and digest molecules.

People with Sandhoff disease don’t have enough of an enzyme called beta-hexosaminidase. Lack of this enzyme causes too much fat (lipids) to build up in cells. The excess fat causes damage to the brain and other body systems, usually leading to death in early childhood.

Sandhoff disease is a severe form of Tay-Sachs disease, another lysosomal disorder.

How common is Sandhoff disease?

Sandhoff disease is very rare, occurring in only 1 of every 1 million people.

Who’s at risk for Sandhoff disease?

Sandhoff disease is genetic, so people who have relatives with Sandhoff disease have a higher chance of getting it. The disease is more common in people with specific ethnic backgrounds:

• Ashkenazi Jewish.
• Creole of northern Argentina.
• Eastern European.
• Lebanese.
• Metis Indians in Saskatchewan, Canada.

What causes Sandhoff disease?

Mutations in the HEXB gene cause Sandhoff disease. Because of the mutations, the body doesn’t make enough beta-hexosaminidase. Without beta-hexosaminidase, the body can’t break down certain fats. The fats reach toxic levels, particularly in the nerve cells in the brain and spinal cord.

What are the symptoms of Sandhoff disease?

The classic form of Sandhoff disease occurs in infants. They appear to be healthy at birth but begin to show symptoms around 3 to 6 months of age. Signs may include:

• Abnormal bone development.
• Awkward movements.
• “Cherry-red” spots on the eyeballs.
• Enlarged head (macrocephaly) or enlarged internal organs (organomegaly), particularly the liver and spleen.
• Exaggerated reactions to loud noises (startle response).
• Frequent respiratory (breathing) infections.
• Slow development in motor skills, such as crawling, sitting up and rolling over.
• Weak muscles, trouble controlling muscles (ataxia) or muscle twitches (myoclonus).

As Sandhoff disease gets worse, babies usually experience:

• Hearing loss.
• Intellectual disabilities.
• Paralysis.
• Seizures.
• Vision loss.
• Early death.

Even more rarely, some people develop Sandhoff disease later, in childhood or adulthood. The symptoms are usually similar but less severe.

How is Sandhoff disease diagnosed?

Healthcare providers diagnose Sandhoff disease by considering:

• Review of symptoms and when they started.
• Discussion of family history and ethnic background.
• Physical examination.
• Blood tests to determine whether beta-hexosaminidase is low or absent.
• Genetic testing to see whether the gene mutation is present.

What treatments are available for Sandhoff disease?

There is no cure for Sandhoff disease. Treatments to reduce symptoms and keep people comfortable may include:

• Anticonvulsants to control seizures.
• Good nutrition.
• Proper hydration.
• Efforts to keep the airway open.

Research is exploring whether other therapies can help, such as:

• Bone marrow transplants.
• Gene therapy.
• Substrate reduction therapy, which changes the molecules involved and interrupts the disease process.
• Stem cell therapy.

Families affected by Sandhoff disease may want to talk to geneticists or genetic counselors. They can help families decide who else should be tested for the genetic mutations.

Can I prevent Sandhoff disease?

There is no way to prevent Sandhoff disease. But geneticists and genetic counselors can help determine who in your family may be at risk. That information can help people decide whether to have children, for example.

What is the outlook for people with Sandhoff disease?

People with Sandhoff disease have a poor prognosis and a short life span. Infants usually deteriorate quickly and die by age 3 or 4, often because of complications from respiratory infections.

What can I ask my healthcare providers about Sandhoff disease?

If your child is diagnosed with Sandhoff disease, consider asking your healthcare providers:

• What disabilities can we expect to see?
• What is our child’s life expectancy?
• What specialists do we need to see?
• How often should we see them?
• How can I keep my child comfortable?
• Should other family members get genetic testing?

How can I best learn to cope with Sandhoff disease?

To help you and your family cope with Sandhoff disease, you can try:

• Counseling.
• Getting involved with organizations that support patients and research.
• Support groups.

A note from Cleveland Clinic

Sandhoff disease is a rare genetic mutation. It leads to toxic levels of lipids in nerve cells in the brain and spinal cord. Affected children have severe symptoms, leading to death in early childhood. Research is underway to further understand Sandhoff disease and potential treatments.