Diagnosing HoFH
A number of tests and checks can be used to diagnose HoFH.
What is HoFH?
Homozygous familial hypercholesteraemia (HoFH) is a form of FH (familial hypercholesterolaemia). This is a condition which is passed down through families in the genes and raises your blood cholesterol to very high levels. HoFH is the more severe form and it raises your cholesterol even higher.
It's very rare. An estimated one in 250,000 people have it.
Without treatment, HoFH can lead to heart disease at a very young age, even in childhood.
HoFH raises your cholesterol from the time you’re born and symptoms often appear in childhood. So, getting diagnosed early is essential for managing cholesterol levels.
How does HoFH lead to early heart disease?
If your LDL cholesterol (sometimes called bad cholesterol) is too high, it gets laid down in your blood vessel walls, clogging them up. This is known as atherosclerosis. Your blood can’t flow around your body as well as it should, putting a strain on your heart and causing disease. Blood clots can also form which can cause a heart attack or stroke.
This process of fat being laid down in the blood vessels is quite common as people grow older and is often caused by an unhealthy lifestyle. But with HoFH it happens much younger, from childhood, and is caused by your genes.
Read more about how high cholesterol can cause heart disease.
How does HoFH raise cholesterol?
HoFH causes problems with the way cholesterol is taken out of the blood, so the cholesterol builds up in your body.
Lets explain…
Normally, your LDL cholesterol (the bad cholesterol) would be taken out of your blood by your liver cells, and certain other cells throughout your body.
These cells have little extensions on them called LDL receptors. Their job is to catch the LDL cholesterol as it passes by in the blood and take it into the cell to be used, stored or broken down. The LDL receptors then return to the edge of the cell to catch more LDL cholesterol.
If you have FH or HoFH, there is a problem with the LDL receptors. Either you don’t have enough of them or they don’t work properly, so they can’t keep your cholesterol levels down.
Your LDL receptors
Receptor defective
Most people with HoFH are known as ‘receptor defective’. This means that up to a quarter (25%) of their LDL receptors are working.
Receptor negative
Others are known as ‘receptor negative’. They have even fewer working receptors – less than 2%.
The type you have will affect which treatments are suitable for you.
How is HoFH passed down in families?
FH and HoFH are passed down in the genes. We have two copies of every gene – one from mum and one from dad:
FH is when you have one faulty copy of a gene
It means you have inherited a faulty copy of a gene from one parent. This will raise your cholesterol.
HoFH is when you have two faulty copies of a gene
It means you have inherited a faulty copy of a gene from both parents. This will raise your cholesterol much higher.
What's it like to live with HoFH?
Hear the frank and honest experiences of the Kara family on living with Homozygous FH, and what it means to father Mohammed, mother Farhana, her sister Abida, and their 7 year old daughter Zunairah.
What are the chances of passing on HoFH?
If two people with FH have four children, on average:
- two children will inherit FH – they will have one faulty gene and one healthy gene
- one child will inherit HoFH – they will have one faulty gene from each parent
- one child will not inherit FH – they will have a healthy gene from each parent.
This means the child has a:
- one in two chance of inheriting FH
- one in four chance of inheriting HoFH
- one in four chance of not inheriting any faulty FH genes.
There are different genes involved
There are a number of different genes involved in FH and HoFH. These genes code for the LDL receptors which take cholesterol out of your blood. If they are faulty, this causes problems with the LDL receptors, causing high cholesterol.
LDL receptor genes
A fault in these genes means you don’t have enough LDL receptors. This is the most common gene involved.
APOB gene (apolipoprotein B)
A fault with this gene means the LDL receptors can’t bind well to cholesterol. This is unusual.
PCSK9 gene
A fault with this gene means that LDL receptors are broken down in the liver, so you don’t have enough LDL receptors.
Types of HoFH
With HoFH, you might have two identical altered genes, or two different ones.
- If the two altered genes are the same – this is called Homozygous FH (HoFH). The word ‘homo’ means ‘the same’.
- If the two altered genes are different – this is called Compound Heterozygous FH but may also be referred to as Homozygous FH (HoFH). The word ‘hetero’ means ‘different’.
Both raise your blood cholesterol to very high levels, so even though the genes are different, the effect on your body is similar.
HoFH and COVID-19 (coronavirus)
Listen to our webinar about what coronavirus means for you if you have HoFH.
Our HEART UK experts clarify what the evidence and guidelines mean for you. We address your questions including who is high risk and who should be shielding.
Learn more about coronavirus and cholesterol.