Sandhoff disease is caused by a mutation in the HexB gene. The HexB gene instructs the production of the enzymes that are essential in the normal function of a nerve cell. The absence or reduction of these essential enzymes causes a fatty substance or lipid called GM2 ganglioside to accumulate abnormally in cells, especially in the nerve cells of the brain. This ongoing accumulation, also called "substrate", causes progressive damage to the cells.

The Juvenile and Late Onset forms of Sandhoff occur when the mutations in the gene allow the beta-Hexosaminidase A and beta-Hexosaminidase B enzymes to function a little bit. Just a small increase in HexA and HexB activity is enough to delay the onset and slow the progression of symptoms.

Inheritance

Sandhoff is an autosomal recessive genetic disorder. Both parents must be a carrier for children to be at risk. There is a 25% chance with each pregnancy the child will be affected.

Sandhoff "breeds true" in a family. If one child is diagnosed with infantile Sandhoff the other children are only at risk for the infantile form. One set of parents could not have children with both the infantile and juvenile forms of the disease.

Gene Location

The gene that causes Sandhoff is located on chromosome 5, specifically 5q13.

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