The science – an overview

Both Tay-Sachs and Sandhoff diseases are lysosomal storage disorders, collectively referred to as the GM2 gangliosidoses. They are caused by a fault in the same metabolic pathway, and are characterised by central nervous system (CNS) degeneration.

The central nervous system (CNS) is made up of your brain and your spinal cord.

Lysosomal storage disorders

A lysosome is a dynamic cellular compartment that contains digestive enzymes to break down and recycle excess or worn-out cell parts.

A lysosome is a dynamic, or active, compartment within a cell. It is responsible for breaking down and recycling large materials that are no longer required. In Tay-Sachs and Sandhoff diseases, the lysosome is unable to do its job.

There are over 80 known lysosomal storage disorders (LSDs) caused by defective genes, and thus are sometimes referred to as genetic disorders.

Genes are one of the basic units of life. They contain the recipes for who you are.

Each lysosomal storage disorder is very rare, and as they are very similar, you may hear the term ‘LSD’ used when referring to either Tay-Sachs or Sandhoff disease.

The GM2 gangliosidoses

A ganglioside is a special type of lipid or fat that is especially found in brain cells. The brain needs gangliosides to function.

The GM2 gangliosidoses are a group of lysosomal storage disorders caused by changes known as mutations, in at least one of three genes: HEXA, HEXB, and GM2A.

All of the GM2 gangliosidoses are rare diseases. As they are similar, you may also hear the term ‘GM2 condition’ used when referring to either Tay-Sachs or Sandhoff disease.

In someone without Tay-Sachs or Sandhoff diseases, the three genes – HEXA, HEXB, and GM2A – contribute to the production of the enzyme beta-hexosaminidase A.. The enzyme beta-hexosaminidase A speeds up (catalyses) the normal breakdown (catabolism) of the GM2 gangliosides.

In someone with one of these diseases, the mutations in the genes result in not enough of the enzyme beta-hexosaminidase A being produced. This leads to a build-up of the GM2 gangliosides inside cells of the brain and spinal cord, causing the clinical symptoms of the disease and resulting in cell dysfunction and death.