The cause of the diseases

An introduction to genetics

• DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms
• Genes are one of the basic units of life. They contain the recipes for who you are. Genes are made up of DNA. They provide the code to make proteins
• Chromosomes are packages of DNA
• Autosomes are the non-sex-related chromosomes
• A mutation is a change or variation on a gene that makes it faulty. The result of the mutation is a gene that does not perform the function it should
• Proteins are large molecules that perform many of the metabolic activities taking place within a cell
• An enzyme is a protein that acts as an activator or catalyst, and it increases the rate of a chemical reaction within the cell
• Beta-hexosaminidase A (HEXA) This is an enzyme that is encoded by the HEXA gene. Beta-hexosaminidase A and the cofactor GM2 activator protein catalyze the breakdown of the ganglioside GM2
• Beta-hexosaminidase B (HEXB) This is an enzyme that is encoded by the HEXB gene. Beta-hexosaminidase B and the cofactor GM2 activator protein catalyze the breakdown of the ganglioside GM2

Genetic disease

We all carry two copies of every autosomal gene; one from each of our parents. Sometimes, one or both copies of a gene is mutated or faulty. The mutation may have been passed on to us from a parent, or may happen spontaneously or randomly.

Some genetic diseases can be caused by one mutated gene, whilst other diseases require two mutated genes.

Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are genetic diseases as they are caused by mutations in certain genes. They are known as autosomal recessive conditions. This means that both copies of the gene need to be mutated in order to cause disease. Most commonly, the individual with the disease has inherited one mutated gene from each of their parents. Rarely, the individual with the disease has inherited one mutated gene from one of their parents, and the other gene has mutated spontaneously (by chance) in the individual.

With autosomal recessive conditions, parents who have one mutated copy of the gene are known as carriers. As they have one functioning copy of the gene, carriers do not develop the disease. As a consequence, parents of children with Tay-Sachs or Sandhoff disease rarely know they are carriers of the disease until after it is diagnosed in their child.

How autosomal recessive inheritance works

Below is an example of autosomal recessive inheritance with the potential offspring. For each child born to the couple:

• There is a 1 in 4 (25%) chance that the child is born with two functioning genes.
  • The child will not have the disease.
  • They will not be a carrier of the disease.
• There is a 1 in 2 (50%) chance that the child is born with one functioning and one mutated gene.
  • The child will not have the disease.
  • They will be a carrier of the disease.
• There is a 1 in 4 (25%) chance that the child is born with two mutated genes.
  • The child will have the disease.
  • They will be a carrier of the disease.