Familial hypercholesterolemia

A hereditary lipid metabolism disorder is sometimes behind a significantly increased cholesterol level. It can lead to heart attacks and strokes from an early age. More about causes, symptoms and therapy

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Familial hypercholesterolemia - briefly explained

Familial hypercholesterolemia is an inherited form of lipid metabolism disorder. Affected people have high levels of LDL cholesterol in their blood. Due to the increased blood lipids, they sometimes suffer from the consequences of arteriosclerosis or cardiovascular diseases at a young age. The treatment consists of a change in diet and medication that lower the level of LDL in the blood. If this is not enough, a type of blood wash is possible, in which LDL is removed from the blood (LDL apharesis).

What is familial hypercholesterolemia?

Familial hypercholesterolemia is a hereditary disorder of lipid metabolism. The level of a certain blood fat - LDL cholesterol - increases by two to ten times the normal value.

If the disease remains untreated, "vascular calcification" (arteriosclerosis) occurs at a young age and as a result serious circulatory disorders, for example in the heart (heart attack) and in the brain (stroke).

Not everyone who the doctor finds high cholesterol levels has familial hypercholesterolemia. There are many possible reasons for abnormal blood lipid levels. You can read more about this, for example, in the guide to increased blood lipid levels. The following article deals exclusively with the familial - i.e. the hereditary - form of hypercholesterolemia.

Cause: Change in the LDL receptor gene

The cause of familial hypercholesterolemia is in most cases a change (mutation) in the LDL receptor gene - that is, the genetic information that contains the "blueprint" for the LDL receptor. This LDL receptor is an important prerequisite for LDL cholesterol being able to get from the blood into the cells. In familial hypercholesterolemia, however, this mechanism does not work properly, so that LDL cholesterol is not or only partially absorbed into the cells. The LDL cholesterol levels in the blood rise. In addition, two other genes are known whose changes lead to familial hypercholesterolemia (ApoB, PCSK9 gene).

LDL carries cholesterol from the liver to the cells

© W & B / Szczesny

So that the water-insoluble cholesterol can be transported in the blood, the fat is bound to certain proteins (lipoproteins). There are two different types of transport proteins: LDL (low density lipoproteins) and HDL (high density lipoproteins). The LDL transports the cholesterol from the liver to the various organs via the blood vessels. The HDL is used to transport cholesterol back from the organs and blood vessel walls. It can thus presumably counteract the development of "hardening of the arteries" (arteriosclerosis) in the vessel wall. On the other hand, increasing HDL with medication does not seem to have a positive effect.

The genetically determined dysfunction of the LDL receptors can vary in severity: Patients are particularly severely affected if no cellular receptors are developed at all. In other variants of the disease, receptors are formed, but they are unable to bind LDL cholesterol. Or the disorder is that the LDL / LDL receptor complex cannot be taken up into the cell. As a result, the LDL cholesterol is increasingly deposited in various tissues, especially the walls of the coronary arteries.

Familial hypercholesterolemia is inherited as an autosomal dominant trait. This means that a modified gene (either inherited from the father or mother) is enough to cause disease.

If the patient has an altered and a healthy gene, then the heterozygous (uneven) form of familial hypercholesterolemia is present. The heterozygous form occurs in one in 300 to 500 people. It is one of the most common congenital metabolic diseases in humans. Without treatment, symptoms often occur as early as the age of 30.

In rare cases, both the mother and the father pass on an altered gene to their child. So it has two altered genes for the LDL receptor. This form of inheritance is called homozygous (pure inheritance). This variant of familial hypercholesterolemia is associated with total cholesterol values ​​of over 500 to 1200 mg / dl (milligrams per deciliter). This corresponds to about 12 to 31 mmol / l (millimoles per liter). It is a very serious illness. Without therapy, the affected patients rarely survive the second decade of life. The homocytogenic form is rarer with a frequency of 1: 1,000,000.


Familial hypercholesterolemia does not initially cause symptoms or physical discomfort. However, the increased circulating LDL cholesterol in the blood is deposited on the vessel walls over time and is therefore a major cause of arteriosclerosis ("hardening of the arteries"). If the vessels are constricted by arteriosclerosis, circulatory disorders arise in the affected organs. Serious complications such as a heart attack can result.

Externally, the lipid metabolism disorder may be noticeable through reddish to yellowish cholesterol deposits on certain areas of the skin, in tendons and the eyes.


The doctor makes the suspected diagnosis of "familial hypercholesterolemia" if he finds high cholesterol levels (total cholesterol and LDL cholesterol) in the blood of his patient and also learns from the person's family history that close relatives have similar high cholesterol levels and suffered from coronary heart disease at an early age or died of sudden cardiac death. "Early" means an age under 55 for men and under 60 for women. Fat deposits in the tendons, so-called tendon xanthomas in the affected person or his / her relatives, arouse the suspicion of familial hypercholesterolemia.

In the milder, heterozygous form of the disease (see section on cause), the LDL cholesterol levels in the blood are in the range of 200 to 400 mg / dl (milligrams per deciliter), with the triglyceride levels usually not being increased. Sometimes the values ​​are also given in millimoles per liter (mmol / l): 200 to 400 mg / dl correspond to around 5 to 10 mmol / l.

The rarer, more severe, homozygous form of the disease has total cholesterol values ​​of 500 mg / dl to 1200 mg / dl (this corresponds to about 12 to 31 mmol / l).