Definition:
Juvenile Onset Sandhoff Disease is an inherited neurodegenerative disease caused by a deficiency of the enzymes Hexosaminidase A (Hex-A) and Hexosaminidase B (Hex-B), which results in the accumulation of certain fats, gangliosides, in the brain. The bodies of individuals affected with Sandhoff are unable to break down GM2 gangliosides, hence the gangliosides build in the lysosomes. Clinical features of Sandhoff and Tay Sachs diseases are largely similar and are indistinguishable, except for the differences in their enzyme deficiency patterns and the hepatosplenomegaly that may occur in Sandhoff Disease. Hexosaminidase A alone is absent in Tay-Sachs disease, whereas both hexosaminidase A and B are absent in Sandhoff Disease. Unlike Tay-Sachs disease, Sandhoff Disease is less prevalent among the Jewish population of Eastern European decent.

Given the differences in the age of onset and the range in the severity of symptoms, physical appearance of this disorder varies greatly from case to case. A later age of onset of symptoms associated with Juvenile Onset Sandhoff Disease/GM2 Gangliosidosis results from extremely low levels of hexosaminidase A enzyme activity, but higher than the levels found in children affected with the classical infantile form.

Symptoms:
Symptoms of the disease present around five years of age and resemble the symptoms associated with the classic and infantile forms of Sandhoff Disease. The disease progression of Juvenile Onset Sandhoff Disease/ GM2 Gangliosidosis is slower than the infantile form of Sandhoff Disease and the end stages typically occur late in adolescence.

Around the age of five, an affected child’s cognition may deteriorate. Ataxia, slurred speech, muscle wasting muscle cramps, tremors, uncoordinated gait, and seizures may occur. Vision may remain intact or decline in the later stages of disease progression.

Inheritance Pattern:
Juvenile Onset Sandhoff Disease/GM2 Gangliosidosis is an autosomal recessive disorder.

Diagnosis and Testing:
Juvenile Onset Sandhoff Disease/GM2 Gangliosidosis is usually diagnosed by measuring Hexosaminidase A and B activity in the blood.

Individuals at risk can undergo genetic screening to determine their carrier status before they have children. Some medical professionals highly recommend DNA testing even for those parents who do not have a family history of Sandhoff Disease. More than 95% of the families that have children with this disorder had no known prior family history of the condition, due to the gene mutation’s silent or recessive nature and to its ability to pass from one generation to another without recognition. Genetic counseling is recommended for individuals who have the mutation.

Life Expectancy:
Life expectancy is 15 years of age or younger due to complications such as respiratory infection.

Treatment:
There is no cure for Juvenile Onset Sandhoff Disease/GM2 Gangliosidosis. Therapies that include enzyme replacement therapy, bone marrow transplants, and blood transfusions have been tried, but have not proven effective in curing this disorder. Preventive genetic counseling is highly encouraged. It is the hope that one day gene therapy will prove to be a cure for Sandhoff Disease.

Patient Groups:
Sandhoff Disease
259 Majorca Road
St. Augustine, FL 32080
http://www.sandhoffdisease.webs.com/
tel: (904) 662-1840
Gina Watkins
gmwatkins74@yahoo.com