The Genetics

So Fabry Disease is usually inherited and runs in families. It’s got to start somewhere though and, like me, you could be the first person in your family to be born with it.

As Fabry is caused by a mutation on the X chromosome it is classed as an X linked genetic disease. If you have the condition your children could inherit it if they get your X chromosome with the mutated gene.

If you have Fabry Disease though it is not definite that your children will inherit the condition. Men will only pass on the mutation if they have daughters. Women have a 50% chance of passing on Fabry Disease to their sons or daughters. The reasons for this are outlined in more detail below.

 

Inheritance

If a parent has Fabry Disease they can pass on the mutated gene to their children. The chances of passing on the mutated gene will depend on whether the parent is male or female, and whether they have sons or daughters.

Male Inheritance Pattern

A male with Fabry Disease will have a mutated X chromosome (shown in red on the image) and a Y chromosome. If he has children, he will give his Y chromosome to any sons, who will be unaffected. Any daughters will get his mutated X chromosome and so will inherit Fabry Disease.

Female Inheritance Pattern

A female with Fabry Disease will have two chromosomes, one of which will have the mutated gene (shown in red on the image). As both male and female children will inherit an X chromosome from their mother, each child will have a 50% chance of inheriting a mutated X chromosome, and so will have a 50% chance of inheriting Fabry Disease.

Fabry Disease Affects Each Individual Differently.

So why does Fabry affect people in different ways? Again, this is down to our genetics and is different in males and females.

Females have two X chromosomes – one from the father and one from the mother. When we are developing in the womb, one of our X chromosomes is randomly deactivated in all cells (except for egg cells for obvious reasons!). This is called X-inactivation, and it is to make sure that we only have one functional copy of an X-chromosome in each cell. So, some cells will have an X chromosome from the mother and some cells will have an X chromosome from the father. If she got a mutated X chromosome from either parent then some of her cells will have this mutated X chromosome. The cells with the mutated X chromosome will have the mal-functioning GLA gene and so will not produce the α-GAL A enzyme. This means that the Gb3 fat will build up in these cells and these are the cells that cause the issues in Fabry Disease. How badly she is affected by Fabry will depend on how many cells and which organs have the mutated gene. 

In males, as they only have one X chromosome, if they inherit a mutated X chromosome from their mother, then all their cells will have this mutation and be adversely affected.

So there is variation in how individuals are affected by Fabry Disease. It depends on which cells have the mutated X chromosome and which do not. 

Male Inheritance

Male%20Inheritence1_edited.jpg

Female Inheritance