Sandhoff Disease

Background and History: 

The biochemical disturbance in Sandhoff disease was described by Konrad Sandhoff, a German chemist, in 1968.  This is one of multiple inherited neurodegenerative disorders and is in many ways similar to Tay-Sachs disease. 

Clinical Correlations: 

Sandhoff disease is a neurodegenerative disorder in which cells of the nervous system become dysfunctional early in life.  The most common form of the disease is manifest in infants between the ages of 3 and 6 months.  Normal development slows and muscle weakness becomes evident.  Infants lose interest in their surroundings and gradually lose vision and hearing.  Blindness results from damage to the cells of the retina.  Seizures are common by one year of age and muscles lose their flexibility.  Progressive paralysis is often seen.  The ‘startle’ response to sounds is exaggerated and maintained longer than normal.  Eventually infants become nonresponsive and death may occur by three years of age.

Rarely both juveniles and adults develop a slightly different form of Sandhoff disease.  Progression of disease is slower in these individuals and they have somewhat different symptoms with some degree of dementia being common. 


This is an autosomal recessive disease in which two copies of the mutation are required for the disorder to be expressed.  The carrier parents with a single copy are clinically normal but each of their children has a 25% chance of inheriting both mutations from them and manifesting the symptoms.

This is a classical hereditary disorder in which a gene mutation produces an ineffective enzyme.  As a result, it is unable to break down certain molecules, which accumulate in tiny organelles in cells called lysosomes.  Being toxic to the cell, these accumulations cause cell death resulting in degeneration of, in this case, the nervous system.  Sandhoff disease is one of a number of such hereditary disorders known as lysosomal storage diseases. 

Diagnosis and Prognosis: 

Pediatricians and neurologists often make the diagnosis early in life.  An ophthalmological can document the damage to the retina and the optic nerve which is responsible for the blindness.  Gene testing must be done to distinguish this disease from Tay-Sachs disease as the clinical picture may not allow distinction.

There is no effective treatment at this time but the results of cell cultures to which gene therapy has been applied have shown promise.  However, treatment at this time is largely supportive with the use of anticonvulsants as indicated.  Good nutrition and maintainence of airways are important. 

Additional Information
Autosomal recessive