Sandhoff disease is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord (central nervous system). This condition is classified into three major types based on the age at which signs and symptoms first appear: infantile, juvenile, and adult.

Sandhoff disease is caused by variants (also known as 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 two 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.

Sandhoff disease is a rare disorder; its frequency varies among populations. This condition appears to be more common in the Creole population of northern Argentina; the Metis Indians in Saskatchewan, Canada; and people from Lebanon.

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

Published Date: December 15, 2021Published By: National Institutes of Health