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Familial hypercholesterolemia | What you need to know

Familial hypercholesterolemia is an autosomal dominant disorder characterized by impaired low-density lipoprotein metabolism.

The disease develops in the gene encoding the low-density lipoprotein receptor LDLR gene As a result of mutation. Mutation of the LDLR gene is the most common cause of familial hypercholesterolemia.

Patients with a mutation in the LDLR gene have significantly elevated levels of low-density lipoproteins in their plasma, which increases the risk of developing atherosclerotic heart disease and its early complications.

75% of familial hypercholesterolemia cases involve a mutation in the LDLR gene and the presence of a defective LDL receptor. A smaller percentage of familial hypercholesterolemia cases are associated with mutations in other genes.

 

Pathophysiology

Low-density lipoprotein binds to the LDL receptor via apolipoprotein B. A defective protein (receptor) synthesized as a result of a mutation in the LDLR gene loses its ability to bind to low-density lipoproteins, which leads to an increase in the level of lipoproteins in the plasma. The defective receptor protein is transported to liver cells, where it is broken down, which further reduces the number of LDL receptors.

 

Epidemiology

The frequency of the heterozygous form of familial hypercholesterolemia (a person has one healthy and one mutated dominant copy of the LDLR gene) is 1:220.

Heterozygous forms of familial hypercholesterolemia (the presence of both mutated copies of the LDLR gene) are very rare and have an incidence of 1:300.

The prevalence of familial hypercholesterolemia varies among ethnic groups and populations. The incidence is much higher in blacks than in whites. The incidence is equal in men and women.

Regardless of ethnicity, cardiovascular complications develop at a much earlier age in men than in women.

 

Risk

Because people with familial hypercholesterolemia have elevated low-density lipoprotein cholesterol levels from an early age, they develop atherosclerotic symptoms early. Coronary artery disease usually appears in boys around age 17 and in girls around age 25. Calcification (hardening) of the coronary arteries occurs in 25% of adults with familial hypercholesterolemia.

 

Diagnosis

Suspicion of the heterozygous form of familial hypercholesterolemia is based on clinical criteria, which are based on the following data:

  • Plasma lipid levels – A level above 190 mg/dL is usually observed.
  • Family history – Presence of coronary artery disease in close relatives.
  • Physical data, such as: Xanthelasmas (cholesterol plaques on the eyelids), xanthomas (cholesterol deposits in and around the tendons of the smooth muscles) and the so-called Arcus cornealis, a cholesterol arc around the cornea.

 

The gold standard of diagnostics

Genetic testing is the gold standard for diagnosing familial hypercholesterolemia. LDLR-Genetic mutations are the most common cause of the disease, although mutations in genes encoding other proteins involved in lipoprotein metabolism are also found (APOBPCSK9 and others). Some mutations may not be detected at all, which may not rule out the disease, especially in the presence of a pronounced clinical and family history.

Detection of the mutation has prognostic value. Regardless of the level of lipoproteins in plasma, mutation carriers have a higher risk of developing atherosclerosis than people without the mutation. Without LDLR gene mutations.

Although familial hypercholesterolemia can be diagnosed based on clinical history, genetic testing is especially important in young people with a family history of the disease. Some types of mutations are associated with increased risk of lipoproteins, which further increases the risk of developing cardiovascular diseases.

Determining the type of specific mutation is sometimes important for selecting a course of treatment.

When a familial form of hypercholesterolemia is suspected, genetic diagnostics is required for both the patient and the closest relatives, who are often unaware of the condition.

 

Treatment

Early initiation of antilipid therapy is important. In untreated heterozygous patients, the first coronary complications occur 20 years earlier than in treated cases.

Familial hypercholesterolemia is treated with statin and non-statin drugs and, rarely, plasma apheresis (extracorporeal filtration to remove excess lipoproteins from plasma). Lifestyle, dietary, and physical activity changes are also essential for effective treatment.

 

Laboratory "Synevo" offers screening for genetic diseases:

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Source:

https://www.ccjm.org/content/87/2/109

Article created with editorial policy in accordance with defined standards

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