Familial Hypercholesterolemia (FH)

What is FH?

Familial hypercholesterolemia (FH) is a rare, inherited form of very high cholesterol. FH is often resistant to standard treatment practices for high cholesterol (such as statins) and usually results in a much higher cholesterol level in the blood stream. Cholesterol is a naturally occurring substance created by the body when digesting animal-based foods. It helps the body create specific hormones, build cell membranes, and digest fat. However, too much cholesterol can cause problems, so there are receptors in the bloodstream to help remove excess cholesterol. But in FH, there are either too few receptors or the receptors don’t work properly to remove cholesterol from the blood. Across the world, FH affects about 1 in 500 people, though specific populations—such as Afrikaners, French Canadians, the Lebanese, and Finns—are much more likely to be affected.

What are the symptoms of FH?

– Xanthomas: collections of cholesterol buildup, usually in the tendons of the hands, fingers, and Achilles heel. – Xanthelasmata: yellowish collections of cholesterol buildup under the skin of the eyelids. – Coronary artery disease: blood vessels (specifically the arteries leading into the heart) become narrow and hard as extra cholesterol in the blood clings to the blood vessel walls and forms plaques. This prevents normal blood flow to the heart, causing angina (chest pain), and potentially, heart attacks. These problems all affect the two main subcategories of FH: Heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH).

What is the difference between HeFH and HoFH?

The main difference between HeFH and HoFH is the genetic mutation. HeFH only needs one mutation of an LDLR, APOB, or PCSK9 gene in order to occur, which means it has autosomal dominant inheritance. HoFH has an autosomal recessive inheritance, which means it needs two mutated genes. Parents typically have signs of hypercholesterolemia and it’s not uncommon for one or both parents to have HeFH. HoFH is rarer (about 1 in 250,000 to 1 in 1 million) and more severe.

What causes FH?

While there are many genes associated with hypercholesterolemia, FH comes from mutations in one or more of the following genes: LDLR, APOB, PCSK9, and LDLRAP1.

Where can I find more information about FH?

• The FH Foundation
• MedlinePlus
• National Organization for Rare Disorders (NORD)