Homozygous familial hypercholesterolemia, usually shortened to HoFH, is a rare inherited condition in which a gene change is passed down from both parents, so LDL cholesterol is extremely high from before birth and arteries begin to narrow much earlier in life than usual [1,2].
This page provides general information. It does not replace advice from a doctor or another qualified healthcare professional.
HoFH and FH are not the same thing, and this is what most people come here to check. Familial hypercholesterolemia, or FH, keeps LDL cholesterol high from birth. Most people who have it inherited one changed gene copy, from one parent: that is heterozygous FH. HoFH is what happens when a changed copy comes from both parents [4,8,12]. Cholesterol is far higher, problems start earlier, and the treatment is different.
Low-density lipoprotein, or LDL, carries most cholesterol through the blood, and liver cells carry tiny structures called LDL receptors that pull it out so the body can clear it [4]. In HoFH those receptors are changed on both copies, so almost none work, LDL builds up from before birth, and it collects in artery walls as fatty patches called plaques that narrow the arteries [1,2,8].
Most people with HoFH are receptor defective, meaning up to a quarter of their receptors still work; others are receptor negative, with under 2 percent working, and which applies affects the treatments. Where the two changed genes differ, the term is compound heterozygous FH [8]. The British spelling is homozygous familial hypercholesterolaemia [4].
HoFH is rare, and the estimate has moved. European expert guidance gives roughly 1 in 250,000 to 1 in 360,000, and calculates that about 30,000 people worldwide have it, with fewer than 5 percent identified [1]. Other sources give between 1 in 250,000 and 1 in 315,000 [2,8,12,16].
Why the older figure of about 1 in a million is no longer used. That number was never a count of anybody. It was calculated by assuming the heterozygous form affected 1 in 500 people, then working out how often two carriers would have a child with both copies changed [6]. The newer figures come from counting real cases, including a Dutch study that found 49 among 104,682 people screened [7].
These figures count people expected to have HoFH, not people diagnosed, and diagnosis often comes late: in an international study the median age at diagnosis was 12 years [20]. It is at least ten times more common in founder populations such as French Canadians, Afrikaners in South Africa and Christian Lebanese communities, and reliable figures are missing for much of Africa, Asia and South America [1].
Genes are the instructions inside our cells, and a gene variant is a change in them [4].
The genes. Changes in both copies of LDLR, which carries the instructions for the LDL receptor, cause 80 to 90 percent of HoFH. Both copies of APOB or of PCSK9 can do something similar, and a genuinely recessive form involves LDLRAP1 [2].
Why the parents almost always have FH themselves. For LDLR, APOB and PCSK9, one changed copy already raises cholesterol, so parents carry a single change and usually have raised LDL cholesterol and a family history of early heart disease [1,2]. Many find out only when their child is diagnosed [16]. A diagnosis therefore leads to cholesterol testing across relatives, which European guidance calls reverse cascade testing. Where both parents have FH, each child has a one in two chance of FH, a one in four chance of HoFH, and a one in four chance of neither [1,8].
Diet, weight and smoking affect cholesterol, though they are not why it is high in HoFH, and doctors rule out thyroid and diabetes problems [3,4].
High cholesterol causes no feeling, so what a person notices are the marks it leaves.
Signs that can appear in childhood. HEART UK lists fatty lumps under the skin (cutaneous xanthomas), swollen tendons on the knuckles and backs of the ankles (tendon xanthomas), a white arc at the edge of the colored part of the eye (corneal arcus), all before age 10, and aortic valve disease before age five [9]. Untreated LDL cholesterol is usually above 400 mg/dL [12].
Heart and artery problems can start young. European guidance reports a first major cardiovascular event at a median age of 31 years, and before age 18 in 4 percent of people, in a group usually diagnosed late and treated too little [1,20]. Narrowing of the aortic valve becomes more common as people live longer, so yearly heart ultrasound scans are routine [1,24].
When to seek urgent help. HoFH itself is not an emergency. A heart attack or a stroke is. Call emergency services immediately for chest pain that feels tight or like squeezing, pain spreading to the arms, neck or jaw, or severe difficulty breathing [30]. Call immediately too for sudden face drooping, weakness in one arm, or slurred speech, even if it stops [31].
Diagnosis usually involves a lipid specialist and rests on four things: a cholesterol blood test, a check for the signs above, questions about heart disease in the family, and genetic testing. It is often late, because nothing hurts and awareness is low [9].
European guidance recommends that an untreated LDL cholesterol above 10 mmol/L, roughly 400 mg/dL, should raise the possibility of HoFH, having lowered the older threshold of 13 mmol/L because some people with genetically confirmed HoFH fell below it [1]. HEART UK gives a practical guide of above 11 mmol/L in a child under 18 and above 13 mmol/L in an adult [9].
Why genetic testing is more useful here. The result carries more weight than in the heterozygous form, because knowing which genes are involved, and how much receptor function is left, helps predict which treatments will work [8]. Orphanet notes that DNA sequencing gives the definitive diagnosis, and testing before birth is possible [2].
Where both parents are known to have FH, European guidance recommends newborn cholesterol screening [1].
There is no cure. Treatment is lifelong, should start at diagnosis where possible, and usually means several treatments together [1].
The backbone. A high-intensity statin plus ezetimibe from diagnosis, rather than a statin alone, at the highest statin dose a person can tolerate, usually rosuvastatin or atorvastatin [1,10].
Why the mechanism matters. Statins, ezetimibe and PCSK9 inhibitors work by increasing LDL receptors on liver cells, so where almost none work there is little to increase. European guidance puts the average reduction from PCSK9-directed treatment in HoFH at around 30 percent, and in one study people with two non-working copies of LDLR saw no response at all [1,3].
Three treatments work regardless of receptor function [1].
Liver transplantation is used rarely, as a last resort, usually in severely affected young children [1].
Availability differs enormously. Several of these medicines are among the most expensive in the world, and a 2025 review calls limited access the largest single barrier to good care worldwide [21]. Most countries have no access to the newer agents, and in less affluent countries a first cardiovascular event came a decade earlier, at a median age of 24.5 years against 37 [1,13].
Care is shared with a lipid specialist. Heart ultrasound scans are recommended at the start and then yearly, with a CT scan of the heart arteries after age 3 [1]. Anyone having apheresis should not take a blood pressure medicine of the type called an ACE inhibitor, since together they can make blood pressure drop sharply [13]. Anyone taking lomitapide needs dietitian support for a low-fat diet, avoids grapefruit and bitter oranges, and takes fat-soluble vitamins [15].
Pregnancy needs planning well ahead. European guidance recommends a heart evaluation beforehand, apheresis during pregnancy where available, and restarting other treatment from the second trimester [1]. The 2026 United States guideline advises deferring most cholesterol-lowering medicines during conception, pregnancy and breastfeeding [25]. Children of a parent with HoFH will have the heterozygous form, so family planning includes testing a partner [1].
Clinical trials are research studies that test whether a treatment works and is safe. HoFH is rare, so studies are fewer and smaller than in common conditions, and they sometimes include children. Deciding whether to look into one is a personal choice, taken in steps.
It is worth being clear on:
Every trial has rules about who can take part, called eligibility criteria. For a study in HoFH they might include a confirmed genetic diagnosis, a particular receptor status, an LDL cholesterol above a set level despite treatment, whether a person already has apheresis, and an age range.
trialport’s medifit helps people consider information related to possible medical suitability. It does not diagnose a condition, confirm eligibility or replace formal screening by the study team.
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Study status checked: 3 August 2026. Research moves, and what is being studied changes, so this describes broad areas, not a fixed list.
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In the United Kingdom, HEART UK is the cholesterol charity and has the clearest patient-facing HoFH pages anywhere, covering diagnosis and treatment, plus a cholesterol helpline answered by email [8,9,10].
In the United States, the Family Heart Foundation runs free care navigation and an online HoFH community, with plain guides to apheresis, lomitapide and evinacumab [12,13,14,15]. The American Heart Association has a short introduction [16], and the NIH Genetic and Rare Diseases Information Center has information specialists [28].
Across Europe, the FH Europe Foundation has a dedicated HoFH page [27], and Orphanet lists expert centers and patient organizations country by country [2]. In Australia and New Zealand, the FH Australasia Network publishes family information and a specialist finder, though it is a clinical network, not a support service [29].
Coverage is thin in much of Asia, the Middle East, Africa and South America, and we have not verified a dedicated HoFH organization there. A hospital lipid clinic or national heart society is the best first contact.
What is the difference between FH and HoFH?
FH usually means one changed gene copy, from one parent. HoFH means a changed copy from both. Cholesterol is far higher, problems start much earlier, and the treatment is different [8,12].
If my child has HoFH, does that mean I have FH?
Almost certainly, for the common forms. Both parents carry a single changed copy, so both usually have raised cholesterol, and many find out only when their child is diagnosed [1,16].
Why do statins not work as well in HoFH?
They work mainly by increasing LDL receptors on liver cells, and where very few work there is little to increase. They are still used with ezetimibe, as the base other treatments are added to [3,10].
Can diet fix it?
No. Healthy eating and activity help and are recommended, though they cannot bring cholesterol down nearly far enough [8,10,16].
Has the outlook improved?
Yes, substantially. Cholesterol-lowering treatment is linked to delayed cardiovascular events and longer survival, and how long people live tracks closely with how far cholesterol is brought down [22,23]. Survival is reported to have nearly doubled over three decades [24].
Written by: trialport editorial team
Reviewed by: Keith Berelowitz, Founder and CEO, trialport
Reviewed on: 3 August 2026
Next review due: 3 August 2027
References last checked: 3 August 2026