Even though the family may not have a history of Sandhoff disease, it is possible for two individuals to have a child with the disease. Since Sandhoff disease was only discovered in 1968, there are years the disease has gone undetected because of misdiagnoses. Pathophysiology
Biallelic pathogenic variants in the HEXB gene cause Sandhoff disease. The gene provides instructions for making a protein crucial to the enzymes beta-hexosaminidase A and beta-hexosaminidase B, which function in nerve cells to break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A breaks down a fatty compound called GM2 ganglioside. Mutations in the HEXB gene disrupt the activity of these enzymes, preventing the breakdown of GM2 ganglioside and other molecules.As a result, progressive damage caused by the resulting buildup of GM2 ganglioside leads to the destruction of nerve cells, causing the signs and symptoms associated with Sandhoff disease. Diagnosis
Sandhoff disease can be detected through the following procedures (before it is apparent through physical examination): a biopsy removing a sample of tissue from the liver, genetic testing, molecular analysis of cells and tissues (to determine the presence of a genetic metabolic disorder), enzyme assay, and occasionally a urinalysis to determine if the above-noted compounds are abnormally stored within the body. For a child to suffer from this disease, both parents must be carriers, and both must transmit the mutation to the child.
Lysosomes contain various enzymes to break down byproducts and toxins to ensure they do not accumulate enough to interfere with the function of the central nervous system.Using restriction enzymes, it was discovered that a mutation on chromosome 5 particularly within the C1214T allele caused the adult onset form of Sandhoff Disease. For the patient showing symptoms of the infantile or juvenile form they have a mutation on exon I207V from their father, and a 16 base pair deletion from their mother which can be located on as many as five exons, exons 1–5. Mutations and polymorphism
Articles regarding Sandhoff disease frequencies among distinct groups of people contain discrepancies from one another. More than 25 mutations have been reported other than novel mutations.One article says that Sandhoff disease is found commonly in individuals with a non-Jewish descent.Others say that it is more commonly in:

the Creole population of northern Argentina
the indigenous Métis in Saskatchewan
Christian Maronite communities from CyprusDiscovery of several mutations in Ashkenazi Jews may reflect ascertainment bias rather than a high population frequency, because Ashkenazi Jews were the targeted population in a mass screening program for Tay-Sachs disease. Several rare SD mutations were discovered as researchers resolved cases of enzyme deficiency among suspected TSD carriers, but no cases of the disease itself have been reported.However, since it is an autosomal recessive disease, it is likely found in any ethnic group passing from generation to generation through carriers without being expressed in their offspring.