Sandhoff disease

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What is Sandhoff Disease?

Sandhoff disease is an inherited, lysosomal storage disorder caused by harmful genetic changes (mutations) in the HEXB gene. The HEXB gene contains instructions for an enzyme called β-hexosaminidase, which is responsible for breaking down harmful substances, primarily a fatty protein known as GM2 ganglioside. Normally, GM2 ganglioside is broken down inside cells and is harmless. In individuals with Sandhoff disease, GM2 ganglioside and other molecules do not get broken down. These molecules then build up in the brain and damage nerve cells. The disease has been broken down into three different types, based on when symptoms first appear.

Infantile (Classic) Form

The classic form of Sandhoff disease appears shortly after birth and is the most severe form of the disease. At around three to six months of age, affected infants start to lose milestones and their muscles will become weaker. They may not be able to roll over, sit up, or crawl. Affected infants will also have an exaggerated startle reaction to noises or touch. Over time, children with Sandhoff disease will develop seizures, vision and hearing loss, intellectual disability, and paralysis. Other symptoms include enlarged organs (organomegaly) and bone abnormalities. A red spot in the eye known as a "cherry-red spot" is characteristic of many lysosomal disorders, including Sandhoff disease.

Juvenile-Onset Form

A milder, rarer form of Sandhoff disease occurs when an individual has mutations that only cause a partial enzyme deficiency. Signs and symptoms vary widely and can begin in childhood or adolescence. Affected individuals may experience muscle weakness, difficulty coordinating movement, speech problems, recurrent respiratory infections, and seizures.

Late-Onset Form

The late-onset form can be difficult to diagnose. Early signs can include clumsiness and muscle weakness in the legs. Over time, people with late-onset Sandhoff disease may require mobility assistance and have difficulty with speech and swallowing. About 40% of affected adults experience mental illness, such as bipolar disorder or psychotic episodes.

How common is Sandhoff Disease?

The incidence of Sandhoff disease is estimated to be 1 in 400,000. The condition may be observed more frequently in certain populations including the Creole population of northern Argentina, the Metis Indians in Saskatchewan, Canada, and people from Lebanon.

How is Sandhoff Disease treated?

Treatment for Sandhoff disease includes supportive care for symptoms, such as medications to control seizures, assistance in getting adequate nutrition, and breathing assistance. There is no cure for the disease.

What is the prognosis for an individual with Sandhoff Disease?

Children with the severe infantile-onset form will often have recurrent seizures by age two and eventually lose muscle function, mental function, and sight, becoming mostly non-responsive to their environment. Death usually occurs by age three and is generally caused by respiratory infections. Children with juvenile-onset Sandhoff disease will show similar health problems, but at an older age, and will also progressively decline. Though challenging and debilitating, the late-onset form does not always shorten life span.