---
title: Familial hypercholesterolaemia
description: What familial hypercholesterolaemia is, why a changed gene leaves a lot of LDL cholesterol in the blood, how it is found in a person and their relatives, how it is treated and when to call an ambulance.
type: disease
aliases:
  - FH
  - familial hypercholesterolemia
  - inherited high cholesterol
  - heterozygous familial hypercholesterolaemia
  - homozygous familial hypercholesterolaemia
  - HeFH
  - HoFH
sources:
  - tier: guideline
    org: minzdrav-rf
    title: Нарушения липидного обмена
    year: 2023
    doi: 10.15829/1560-4071-2023-5471
    url: https://cr.minzdrav.gov.ru/view-cr/752_1
  - tier: guideline
    org: esc
    title: '2019 Рекомендации ESC/EAS по лечению дислипидемий: модификация липидов для снижения сердечно-сосудистого риска'
    year: 2020
    doi: 10.15829/1560-4071-2020-3826
    url: https://doi.org/10.15829/1560-4071-2020-3826
  - tier: guideline
    org: nice
    title: 'Familial hypercholesterolaemia: identification and management (CG71)'
    year: 2019
    url: https://www.nice.org.uk/guidance/cg71
  - tier: reference
    org: msd-manuals
    title: Dyslipidemia (Hyperlipidemia)
    year: 2025
    url: https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/lipid-disorders/dyslipidemia
  - tier: reference
    org: msd-manuals
    title: Dyslipidemia
    year: 2025
    url: https://www.msdmanuals.com/home/hormonal-and-metabolic-disorders/cholesterol-disorders/dyslipidemia
sources_checked: 2026-10-13
review: null
---

Familial hypercholesterolaemia (FH) is an inherited disorder of lipid metabolism: because of a change in a single gene, the level of low-density lipoprotein (LDL) cholesterol in the blood is markedly raised and atherosclerosis develops early, usually at a young age.<Cite n={1} /> It is the most common inherited disorder of this kind: its milder, heterozygous form affects on average 1 in 200–250 people.<Cite n={1} /> Yet only a small proportion of people with FH are identified and treated.<Cite n={2} /> General information about cholesterol, the lipid blood test and treatment targets is in the article on [high cholesterol (dyslipidaemia)](../dyslipidemia/).

<Diagram name="familial-hypercholesterolemia">
  <p slot="normal">
    The diagram shows a liver cell and the blood next to it. LDL receptors sit on the surface of
    liver cells: they bind LDL particles and remove them from the bloodstream.<Cite n={1} /> A
    particle attaches to the receptor through its protein, apoB100.<Cite n={1} />
  </p>
  <p slot="disease">
    In familial hypercholesterolaemia a changed gene means that cells take up LDL particles less
    well, and LDL cholesterol in the blood rises.<Cite n={1} /> Most often the gene of the receptor
    itself is changed; different changes impair its work partly or completely.<Cite n={[1, 2]} />
  </p>
</Diagram>

## Why it happens

<Patient>

Cholesterol is carried in the blood by LDL particles. Liver cells play an important part in clearing them from the blood: on their surface there are receptors that take up these particles.<Cite n={1} /> In familial hypercholesterolaemia a gene needed for this work is changed, so LDL particles leave the blood less well and LDL cholesterol stays high.<Cite n={1} />

The condition is inherited.<Cite n={1} /> If the changed gene came from one parent, this is the heterozygous form; if from both parents, the homozygous form.<Cite n={[3, 5]} /> The homozygous form is much more severe<Cite n={5} /> and very rare: in European data, about 1 person in 160,000–300,000.<Cite n={1} />

High LDL cholesterol speeds up atherosclerosis, so heart disease appears early.<Cite n={1} /> Smoking, high blood pressure, diabetes and obesity speed it up even more.<Cite n={5} />

</Patient>

<Student>

FH is a genetically determined monogenic disorder of lipid metabolism with a predominantly autosomal dominant pattern of inheritance; heterozygous (HeFH) and homozygous (HoFH) forms are distinguished.<Cite n={1} /> According to an epidemiological study in several regions of Russia, the prevalence of HeFH ranges from 1:108 to 1:173.<Cite n={1} />

It is caused by defects in genes of proteins involved in lipoprotein metabolism that impair the uptake of LDL particles by cells.<Cite n={1} /> The most common cause is a mutation in the LDL receptor gene (LDLR); the receptor is located mainly on the surface of hepatocytes, and more than 1,600 such mutations are known.<Cite n={1} /> Less often the APOB gene is affected, which encodes apolipoprotein B100, responsible for binding LDL to the receptor; less often still the PCSK9 gene, which encodes a serine protease involved in the degradation of the LDL receptor.<Cite n={1} /> LDLR and APOB mutations cause loss of function,<Cite n={2} /> whereas PCSK9 mutations cause gain of function, so LDL receptors are degraded faster.<Cite n={4} /> With complete loss of receptor function, hypercholesterolaemia and cardiovascular disease (CVD) are most severe.<Cite n={2} />

</Student>

## Symptoms

<Patient>

For a long time familial hypercholesterolaemia gives no sign of itself.<Cite n={1} /> Sometimes fatty deposits can be seen: firm yellow thickenings of the Achilles tendons and of the tendons on the back of the hands (tendon xanthomas), and lumps on the elbows and knees.<Cite n={[1, 3]} /> But not everyone has xanthomas, and in childhood they rarely appear, so their absence does not rule the condition out.<Cite n={[3, 5]} /> Yellow plaques on the eyelids (xanthelasmas) occur in this condition but are also found in people with normal cholesterol.<Cite n={5} />

The main danger is early coronary heart disease: angina and heart attack.<Cite n={[1, 5]} /> Without treatment, people with the heterozygous form usually develop heart and blood vessel disease before 55 in men and before 60 in women.<Cite n={2} /> Early diagnosis and treatment markedly reduce this risk.<Cite n={[2, 5]} />

</Patient>

<Student>

Tendon xanthomas are firm, slowly enlarging yellow growths over the Achilles tendons and the finger extensor tendons; tuberous xanthomas occur in FH over the extensor surfaces of the knees and elbows and on the buttocks.<Cite n={1} /> Corneal arcus has diagnostic value in people younger than 40–45 years.<Cite n={1} />

Rapid progression of atherosclerosis leads to early onset of atherosclerotic CVD, most often coronary heart disease (CHD).<Cite n={1} /> In heterozygous FH the risk of CVD is increased at least tenfold.<Cite n={2} /> Homozygous FH is a rare life-threatening disease with widespread xanthomatosis and early, progressive CVD; without treatment most patients develop CHD and [aortic stenosis](../aortic-stenosis/) before the age of 20.<Cite n={2} />

</Student>

## How it is diagnosed

<Patient>

Familial hypercholesterolaemia is looked for with a blood cholesterol test and the family history.<Cite n={1} /> It is suspected when LDL cholesterol is very high, when there are xanthomas, when a heart attack or another atherosclerotic disease of the blood vessels came early (before 55 in men, before 60 in women) in the person or in their relatives, and when someone in the family died suddenly from cardiac arrest.<Cite n={[1, 2]} /> First the doctor rules out other causes of high cholesterol and measures LDL cholesterol more than once.<Cite n={[1, 3]} />

The diagnosis is made using special criteria, and a DNA test can confirm it.<Cite n={[1, 2]} /> When the condition is found in one person, their relatives are tested, because they may have it too.<Cite n={[1, 2]} /> Doctors encourage people to tell their relatives about the possible risk.<Cite n={3} /> Children of an affected parent are offered a DNA test as early as possible.<Cite n={3} />

</Patient>

<Student>

To diagnose HeFH in adults, the Russian Ministry of Health guideline recommends the Dutch Lipid Clinic Network (DLCN) criteria; in children and when LDL cholesterol (LDL-C) cannot be measured, the Simon Broome criteria; and for HoFH, the criteria of the European Atherosclerosis Society experts.<Cite n={1} /> By the DLCN score, HeFH may be definite, probable or possible; the diagnosis is made only for the definite or probable form.<Cite n={1} /> The score is based on personal and family medical history, clinical signs, LDL-C concentration and DNA testing.<Cite n={3} />

FH can be diagnosed on clinical criteria without molecular genetic testing, but an identified mutation makes the diagnosis and cascade screening easier.<Cite n={1} /> A mutation is found in 60–80% of patients with clinically definite or possible HeFH.<Cite n={2} /> Cascade screening is recommended for first-, second- and, when possible, third-degree relatives; if a pathogenic or likely pathogenic variant is found in a relative, FH is diagnosed even if their LDL-C is below the diagnostic values.<Cite n={1} /> When DNA testing has excluded FH in a family member, their risk is managed as in the general population.<Cite n={3} />

Patients with FH and atherosclerotic CVD are classed as very high risk, and those without CVD as high risk.<Cite n={[1, 2]} /> NICE advises against using CHD risk estimation tools in them, because they are already at high risk of premature CHD.<Cite n={3} />

</Student>

## How it is treated

<Patient>

Cholesterol-lowering medicines are started as soon as the diagnosis is made and are usually taken for life.<Cite n={[1, 3]} /> Starting early matters: the harm depends on how long cholesterol has been high.<Cite n={2} /> Often one medicine is not enough, and the doctor adds a second.<Cite n={2} /> Which medicines are needed and how far to lower LDL cholesterol is for the doctor to decide.

Lifestyle (diet, physical activity, a healthy weight) is part of treatment but not a substitute for medicines.<Cite n={[3, 5]} /> It is especially important not to smoke and not to start smoking, children included.<Cite n={3} /> If medicines are not enough, LDL is filtered out of the blood with a special machine (apheresis); in the severe homozygous form a liver transplant is sometimes considered.<Cite n={[3, 5]} />

In general, pregnancy and breastfeeding are not ruled out, but pregnancy is planned in advance with a doctor: cholesterol-lowering medicines are not prescribed when planning a pregnancy, during pregnancy or while breastfeeding.<Cite n={[1, 3]} /> People with FH are offered regular reviews with a specialist.<Cite n={3} />

</Patient>

<Student>

Lipid-lowering therapy is started immediately after the diagnosis is made; a statin is recommended as initial therapy for all patients with FH, and other drug classes are added if the target is not reached.<Cite n={1} /> According to ESC, most cases need a combination of a statin with a cholesterol absorption inhibitor, and PCSK9 inhibitors are recommended for very-high-risk patients who do not reach the target.<Cite n={2} /> LDL-C targets depend on the risk category (see the article on [dyslipidaemia](../dyslipidemia/)).<Cite n={1} />

Treatment of children with FH includes lifestyle changes and statins; NICE says lipid-modifying drug therapy should usually be considered by the age of 10 years.<Cite n={[2, 3]} /> In children with homozygous FH, treatment is begun when the diagnosis is made.<Cite n={4} /> Homozygous FH is an absolute indication for extracorporeal LDL removal (plasmapheresis, plasma sorption), and severe heterozygous FH an indication when drugs are insufficient or not tolerated.<Cite n={1} /> NICE suggests considering liver transplantation in HoFH after lipid-modifying drug therapy and LDL apheresis.<Cite n={3} />

</Student>

## When to call an ambulance

Familial hypercholesterolaemia itself causes no symptoms for a long time, but its main complication is coronary heart disease, which in this condition starts early, often at a young age.<Cite n={1} /> A person with FH who has signs of acute coronary syndrome, that is a heart attack or a threatened heart attack, should be taken to hospital as an emergency, as anyone else would be.<Cite n={3} /> For chest pain or pressure, severe shortness of breath or fainting, call your local emergency number (112 in the EU, 911 in the US and Canada, 999 in the UK) at once: this is the site's general safety rule. The signs of a heart attack are described in the article on [coronary heart disease](../coronary-heart-disease/).

<Quiz />