Sandhoff disease is caused by the absence or significantly reduced level of two vital enzymes:
Hexosaminidase A (Hex A)
Hexosaminidase B (Hex B). Without Hex A & Hex B, a fatty substance or lipid called
GM2 ganglioside accumulates 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 allow the Hex A and Hex B enzymes to function a little bit. Just a small increase in Hex A and Hex B activity is enough to delay the onset and slow the progression of symptoms.
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.
The
gene that causes Sandhoff is located on
chromosome 5, specifically 5q13.
Read more about inheritance