FH is a genetic disorder that causes high levels of low-density lipoprotein cholesterol in your blood. If you have one or two copies of the same genes, doctors will classify FH as either Homozygous or Heterozygous.
While FH is relatively common, affecting at least 1 out of 250 people, the HoFH subtype is very rare. Fewer than
This article will discuss the less common but more severe HoFH subtype and how it compares with HeFH.
Like other genetic mutations, you inherit FH from one or both of your parents. HeFH results when you inherit the mutated gene from one parent. You have HoFH if you inherited the mutated genes from both parents.
Having FH means your body can’t recycle LDL-C as it should. This leaves atypically high LDL-C levels in your bloodstream. LDL-C levels are higher in HoFH than they are in HeFH.
A family history of this genemutation is one of the risk factors for FH. If both of your parents have a related gene, you may be at a higher risk of developing HoFH.
FH is also generally more prevalent in the following populations:
- Afrikaners in South Africa.
- Ashkenazi Jews from Lithuania
- French Canadians are also called French Canadians.
- Christians from Lebanon.
HoFH and HeFH are compared.
||Most cases of FH are HeFH|
|Causes||Multiple mutations in LDL receptor genes that you inherit from both parents||Single or multiple of the same mutations that you inherit from one parent only|
|LDL-C levels||Above 400 mg/dL||More than
|Symptoms||Visible nodules called xanthomas
Cardiovascular-related symptoms, such as chest pain
|Doesn’t usually cause symptoms until the development of heart disease
Possible chest pain and other symptoms in the case of related heart disease
Certain lipid-lowering medications approved specifically for HoFH
|Cholesterol-lowering medications and injections
Possible LDL apheresis
- chest pain or discomfort
- A heart attack.
- peripheral vascular disease, which may cause leg discomfort
- A type of cardiovascular disease called anaphylactic aneurysm.
People with HoFH may also experience the above symptoms with CAD caused by FH. The key difference is that these symptoms may appear earlier in life, with vascular diseases developing by your teenage years.
Children with HoFH are also more likely to develop cholesterol-containing skin nodules called xanthomas. While people with HeFH may develop xanthomas later in life, these raised, yellowish nodules may appear in early childhood in people with HoFH.
A child with HoFH may have xanthomas in the following areas:
- The hands are touching.
- The elbows.
- The knees.
- The buttocks.
Children with HoFH may also develop corneal arcus at a young age. This is another condition where cholesterol deposits build up — in this case, around the inner edge of the cornea in your eye.
It is possible that HoFH will be identified early in life due to heart related symptoms. You have to undergo testing to be sure that you have this genetic condition.
A doctor may use the following diagnostic tools:
- A physical exam is done.
- Personal and family medical history is evaluated.
- A focus on the levels of cholesterol in the blood.
- other blood tests to help rule out other possible causes of high LDL-C, including kidney and thyroid diseases
Additionally, a doctor may use a scoring system, such as the Dutch Lipid Clinic Network Score, to help determine the likelihood that you have FH.
“The only way to confirm that you have the FH’s homozygous type is to have genetic testing.”
If you have a family history of FH, it’s important to undergo genetic testing to see if you’re carrying the genetic mutations that might increase your risk of this condition. All first degree relatives, such as parents, children, and siblings, also
If you have a family history of early heart disease or are currently showing symptoms of HoFH, a doctor may recommend genetic testing.
HoFH requires aggressive treatment as soon as possible. This will help lower your risk of developing serious vascular disease at a young age.
First-line treatments for HeFH include cholesterol-lowering medications, such as statins. However, such treatments are rarely effective in HoFH due to the high level of LDL cholesterol in the bloodstream.
Instead, a doctor will likely recommend medications approved by the Food and Drug Administration (FDA) specifically for treating HoFH. These include:
- PCSK9 inhibitors: These may induce your liver to remove LDL cholesterol. Doctors use these inhibitors specifically for people with PCSK9 genetic mutations confirmed by testing. They’re available in
- Lomitapide (Juxtapid): When used along with a low fat diet, this lipid-lowering medication may help treat HoFH, especially in cases where heart disease may be present. Your doctor
may gradually increaseyour dose based on your tolerance level.
- Mipomersen (Kynamro): Approved by the FDA for HoFH
in 2013, this injectable treatment is for those who don’t experience results from other treatments.
Another treatment doctors use to treat HoFH is LDL apheresis, which removes LDL cholesterol from the blood through a system similar to kidney dialysis. For the best results, you may need to repeat this treatment
If their LDL-C levels are high, people with HeFH may have their LDL apheresis done.
If it is found and treated early, HeFH is manageable.
However, HoFH is far more aggressive. Experts estimate that without appropriate treatment, children with HoFH may develop severe CAD by their mid-20s. Without aggressive treatment, HoFH has a high mortality rate before the age of 30.
A 25-year study of 133 people with HoFH showed that aggressive treatment to lower LDL-C levels significantly improved their outlook.
HoFH is a rare type of FH. HoFH causes significant levels of cholesterol in the blood, which is usually above 400. HoFH may be deadly in early adulthood if not treated early.
There are treatment options for this type of FH. If you or a family member has a history of FH or early heart disease, you should talk with a doctor about genetic testing.