What is familial hypercholesterolaemia (FH)?

What is genetic high cholesterol?

Familial hypercholesterolaemia (FH for short) is an inherited condition which can cause extremely high cholesterol levels. It's passed down through families in the genes. 

Without treatment, FH can lead to heart disease at a very young age. But once it's been diagnosed, it can be treated with medicines and a healthy lifestyle.

FH means your cholesterol can become much higher than other people's even if you have a very healthy lifestyle, because it affects the way cholesterol is broken down in the body. Dr Sarah Jarvis explains more in this video.


Read about the new pilot screening service to find children with FH


What does 'familial hypercholesterolaemia' mean?

The ‘hyper’ part of hypercholesterolaemia means ‘too high’. The ‘cholesterol’ part simply means cholesterol, a type of fat, and ‘aemia’ means ‘in the blood’. So, hypercholesterolaemia means too much cholesterol in the blood. And this can clog up your blood vessels.

The ‘familial’ part of familial hypercholesterolaemia simply means it runs in families. FH is passed from parent to child in the genes, and it’s usually possible to trace FH back through several generations.

With FH, there is a fault in one of the genes involved in removing cholesterol from the blood.

Learn about getting a genetic test to see if you have a genetic condition

How does FH raise cholesterol?

Cholesterol is made by your liver and carried in your blood all around your body. It’s taken out of your blood and into your cells to be used or stored, and any excess cholesterol can be carried back to your liver and broken down.

FH can cause problems with these natural processes. LDL cholesterol (sometimes known as bad cholesterol) can’t be taken out of your blood quickly or easily, so your cholesterol can build up.

Your genes play a role in your cholesterol levels because they affect the way your cells take cholesterol out of your blood. FH happens when you inherit a faulty gene from one of your parents – the proper name for a fault or alteration in a gene is a mutation.

There are three main genes, or sets of genes, which can be involved in FH

Our liver cells and many other cells in our bodies have small structures attached to them called LDL receptors. They have an important job in keeping blood cholesterol down.

When LDL cholesterol in the blood passes by, it attaches to an LDL receptor which takes it into the cell. The cholesterol is used or stored for later, or broken down by liver cells. The LDL receptor then returns to the surface of the cell, ready to bind to more cholesterol in the blood.

With FH, the liver cells can’t take LDL out of your blood. And this is down to faults or mutations in a few specific genes.

LDL receptor genes

Most people with FH have a fault in one of these genes. It means you don’t have enough LDL receptors, so cholesterol builds up in the blood.

APOB gene (apolipoprotein B)

Only two or three out of every 100 people with FH have a fault with this gene. It means LDL cholesterol can’t bind well to LDL receptors. LDL is taken out of the blood too slowly, and cholesterol in the blood stays high.

PCSK9 gene

Only a few people have this type of FH. A fault with this gene means that LDL receptors are broken down in the liver, so they can’t take cholesterol out of your blood.

Find information about coronavirus for people with FH



Other conditions

There are other genetic conditions which can cause high cholesterol. For example, polygenic hypercholesterolaemia, where instead of one gene causing the high cholesterol, small problems with many genes all add up to raise cholesterol. 

There is also a type of FH where you inherit two faulty genes rather than one, and it raises cholesterol levels further. This is known as Homozygous FH, (HoFH).

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