How do people get Gaucher disease?
‘Genes’ are tiny packets of information kept in every cell of the body on long strands of DNA called chromosomes. There are about 20,000 genes that provide a code that tells cells what to do, a bit like a computer program for the body. All our genes are passed on to us by our parents. Whether or not a person has Gaucher disease depends on the acid-β glucosidase (or GBA) genes that they have received from their parents.
In people with Gaucher disease, the GBA gene that tells cells to make acid-β glucosidase is faulty (this is sometimes called a mutation) which means less of the enzyme is made, or the enzyme which is made doesn’t work well, or in some cases, no enzyme is made at all. This leads to a build-up of the fatty substance called glucosylceramide in the macrophages (white blood cells) and gives health problems in different organs of the body (see ‘What is Gaucher disease’ and ‘What causes Gaucher disease’ sections).
A person with Gaucher disease could have done nothing to stop themselves from having the condition; it is caused by the faulty GBA genes passed to them from their parents.
How is Gaucher disease passed on in families?
Each of us have two sets of genes in all of our cells – with one set coming from our mother and one from our father. The set of GBA genes passed (inherited) from ones parents will decide whether a person will have Gaucher disease or not:
- If both genes in the pair are normal, the person will not have Gaucher disease
- If both genes in the pair are faulty the person will have Gaucher disease
- If one gene is normal and the other is faulty, the person will be a ‘carrier’ of Gaucher disease
To develop the signs and symptoms of Gaucher disease, one has to inherit a faulty GBA gene from both of their parents – this is called an ‘autosomal recessive’ disease.
Carriers do not have Gaucher disease themselves, but they do have one faulty GBA gene and may pass this on to their children. Although Gaucher disease carriers have one faulty GBA gene, their other normal GBA gene means that acid-β glucosidase can be made, and the harmful build-up of glucosylceramide does not happen. Even though the amount of acid-β glucosidase that they make is usually lower than normal, carriers have no symptoms of Gaucher disease and may not know that they have one faulty GBA gene.
The odds of passing Gaucher disease from parents to children
Gaucher disease is inherited in an ‘autosomal recessive’ manner. To understand what this means in practice, imagine that a man and woman are both carriers of Gaucher disease – they do not have the disease themselves but each carries one faulty GBA gene. Each time they have a child together:
- There is a 1 in 4 (i.e. 25%) chance that the child will inherit 2 normal GBA genes and will be free of the disease (they will not be a sufferer or carrier of Gaucher disease)
- There is a 2 in 4 (i.e. 50%) chance that the child will inherit 1 faulty GBA gene and will be a carrier of Gaucher disease (but not be affected by the disease itself)
- There is a 1 in 4 (i.e. 25%) chance that the child will inherit 2 faulty GBA genes and will have Gaucher disease
Both parents are carriers of Gaucher disease
If both parents do not have Gaucher disease or are not carriers of the faulty gene, none of their children will be affected by Gaucher disease or be carriers.