Definition

What is Sandhoff disease?

Sandhoff disease is an inherited lipid storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord.

The most common and severe form of Sandhoff disease becomes apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months when their development slows and muscles used for movement weaken. Other forms of Sandhoff disease have been described where much milder signs and symptoms begin in childhood, adolescence, or adulthood. These forms are very rare.

How common is Sandhoff disease?

Sandhoff disease is a very rare disorder that affects males and females in equal numbers. This disorder occurs in people of many different ethnic backgrounds. Sandhoff disease may be more common in the Creole population of northern Argentina, the Metis Indians in Saskatchewan, Canada and individuals of Lebanese ancestry. Please discuss with your doctor for further information.

Symptoms

What are the symptoms of Sandhoff disease?

Infants with the classic form of Sandhoff disease typically appear normal until the age of 3 to 6 months when their development slows and muscles used for movement weaken. Affected infants typically lose motor skills such as turning over, sitting, and crawling. They may also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Sandhoff disease may experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified through an eye examination, is characteristic of this disorder. Some affected children also have an enlarged liver and spleen, frequent respiratory infections, or bone abnormalities. Children with the severe infantile form of Sandhoff disease usually live only into early childhood.

Forms of Sandhoff disease where the symptoms develop after infancy are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness.

There may be some symptoms not listed above. If you have any concerns about a symptom, please consult your doctor.

When should I see my doctor?

If you or your loved one has any signs or symptoms listed above or you have any questions, please consult with your doctor. Everyone’s body acts differently. It is always best to discuss with your doctor what is best for your situation.

Causes

What causes Sandhoff disease?

Sandhoff disease is caused by mutations in the HEXB gene.

The HEXB gene provides instructions for making a protein that is part of two critical enzymes in the nervous system, beta-hexosaminidase A and beta-hexosaminidase B. These enzymes are located in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, these enzymes break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A helps break down a fatty substance called GM2 ganglioside.

Mutations in the HEXB gene disrupt the activity of beta-hexosaminidase A and beta-hexosaminidase B, which prevents these enzymes from breaking down GM2 ganglioside and other molecules. As a result, these compounds can accumulate to toxic levels, particularly in neurons of the brain and spinal cord. A buildup of GM2 ganglioside leads to the progressive destruction of these neurons, which causes many of the signs and symptoms of Sandhoff disease.

Risk factors

What increases my risk for Sandhoff disease?

Sandhoff disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Please consult with your doctor for further information.

Diagnosis & treatment

The information provided is not a substitute for any medical advice. ALWAYS consult with your doctor for more information.

How is Sandhoff disease diagnosed?

Sandhoff disease can be diagnosed by performing an enzyme assay to determine activity of the hexosaminidase A and B enzymes. Affected individuals have absent or reduced activity of both enzymes.

Molecular genetic (DNA) testing is available to determine the specific gene mutation that is present in the beta subunit of the Hexosaminidase B gene and confirm the diagnosis.

How is Sandhoff disease treated?

There is no specific treatment or cure for Sandhoff disease. Management is symptomatic and supportive.

Anticonvulsants may be used to control seizures.

Death from respiratory infection usually occurs by age three for the infantile form of the disease.

Genetic counseling is recommended for affected individuals and their families.

Lifestyle changes & home remedies

What are some lifestyle changes or home remedies that can help me manage Sandhoff disease?

  • Having proper nutrition
  • Staying hydration
  • Keeping the airway open

If you have any questions, please consult with your doctor to better understand the best solution for you.

Hello Health Group does not provide medical advice, diagnosis or treatment.

Sources

Review Date: February 6, 2018 | Last Modified: February 6, 2018

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