Homozygous Familial Hypercholesterolemia 

There are two forms of Familial Hypercholesterolemia (FH): Heterozygous Familial Hypercholesterolemia (HeFH) and Homozygous Familial Hypercholesterolemia (HoFH). The most serious type of FH is HoFH. Untreated, HoFH often causes heart disease in the early teen years and sometimes even in early childhood. It is much less common than HeFH, but lives can be saved if it is identified and treated early in childhood.  When a person with HoFH is not treated with medications, the low-density lipoprotein cholesterol (LDL-C, “bad cholesterol”) level is between 500-1000 mg/dL-over 4 times the normal level.

On this page you will learn about HoFH, when and where to seek a doctor if you think that you have HoFH, and lifestyle changes, medications and other treatment to help manage HoFH. This page will also help connect you or your child with others who suffer from the same problem.
See our HoFH Infographic


What Makes HoFH different from HeFH?

Parents can give a disorder to their children through their DNA, which is made up of genes. Genes have all the characteristics that a person gets from their parents (such as eye color, hair color, height, etc.), and some may be mutated and not work properly.  When a person gets a mutated gene, they can have mild or severe problems depending on the type of mutation. 

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There are three different genes that may be mutated in HoFH. The most common gene codes for a protein called the LDL receptor. LDL receptors in the liver remove LDL-C from the blood. If a person has a mutated gene for the LDL receptor, the level of LDL-C in his or her blood will increase. Genes that make other proteins, such as PCSK9 and apolipoprotein B (ApoB), may also be mutated and decrease the removal of LDL-C from the blood.

If a person has a mutated gene for any of these proteins, the level of cholesterol in her or her blood will increase.

People can have one or two of these mutated genes. When a person has one of these mutated genes (either for the LDL receptor, PCSK9, or ApoB), he or she has HeFH. So, the difference between HeFH and HoFH is that a person with HoFH has two mutated genes. Two mutated genes greatly increase a person’s blood cholesterol level and the risk of a heart attack.


How Common is HoFH?

Until recently, it was believed that 1/500 people (630,000 people in the U.S.) had HeFH while about 1/1,000,000 people (300 people in the U.S.) had HoFH. New studies suggest that HeFH and HoFH are more common. It is now believed that 1/250 people (or 1.3 million people in the U.S. alone) have HeFH and 1/160,000 (or 2,000 people in the U.S.) have HoFH. Even though HoFH is still rare, it is a lot more common than we once thought. If you think that you or someone you know may have FH, talk to your doctor. To find an FH specialist, click here


How do I Know if I Have HoFH?

HoFH can be diagnosed through genetic testing or a clinical diagnosis. Unfortunately, genetic testing is not commonly used in some countries including the U.S. Also, not everyone with HoFH has the same signs and symptoms. If you have any of the below signs or symptoms, please talk to your doctor:


Level of LDL-C:
This is extremely important. The higher the LDL-C, the more likely it is that a person has HoFH (LDL-C > 500 mg/dL).


Physical Characteristics:

1. Xanthomas

XanthXanthomasHandomas are collections of cholesterol under the skin or tendons. They are yellow bumps that can be small and hard to see. These are often found in the folds of skin and buttocks in children. Also, there can be xanthomas on the tendons at the ankles and hands. Children often have xanthomas without any signs of heart problems in early childhood. 




2. Corneal Arcus

Corneal ArcusA corneal arcus is a greyish-white ring of cholesterol around the iris. A corneal arcus at a young age can mean that the child has HoFH.





 



3. Heart and blood vessel disease

HomozygousA heart murmur may be the result of narrowing of the opening of the aortic valve by cholesterol buildup. A child with aortic valve disease and high LDL-C may have HoFH. Cholesterol plaque builds up in the coronary arteries supplying blood to the heart, the carotids taking blood to the brain, the arteries to the kidneys, and other arteries. Blockage of the flow of blood to the heart may cause chest pain, shortness of breath, dizziness, or irregular heartbeats. Special tests of the heart such as a EKG, echocardiogram, CT angiogram or cardiac catheterization are recommended to check the aortic valve and coronary arteries at diagnosis and at least every 5 years
 


Family History:
This is key. If both parents have very high LDL-C (>190 mg/dL) and/or history of heart disease before age 55-65, this may suggest that they both have FH and can each pass a mutated gene to their children. When each parent has HeFH, by chance, 1 of 4 children will have a normal cholesterol level, 2 of 4 children will have HeFH and 1 of 4 children will have HoFH.  Prenatal DNA testing may be available if the mutations are identified in the parents. Download our family tree to track your family history.


Response to cholesterol-lowering medications
:
If a person is living a healthy lifestyle and taking cholesterol-lowering medications like statins, and/or cholesterol absorption inhibitors, and/or bile acid sequestrates and still has high cholesterol level (> 300 mg/dL), they may have HoFH.

 


Treating and Managing HoFH:

It is important to remember that HoFH is a serious medical condition and is life-threatening if not treated at a young age, preferably beginning in early childhood. A child or adult with HoFH needs life-long medications and other specialized treatments to lower the LDL-C and prevent heart attacks. This requires the expertise of a lipid specialist.

For more information on treatment, click here.