Disease name: Familial Hypercholesterolemia

ICD-10 Disease Code: E78.01 - Familial hypercholesterolemia

ICD-10 Disease Group: E78 - Disorders of lipoprotein metabolism and other lipidemias

General description:

Familial hypercholesterolemia (FH) is a genetic disorder characterised by elevated levels of low-density lipoprotein cholesterol (LDL-C) which results in a greater risk of developing heart disease. Untreated individuals have a 20-fold increased likelihood of developing heart disease. The disorder is caused by an inherited genetic mutation that leads to an inability to remove the extra cholesterol that builds up in the blood. The aberrant buildup of cholesterol can lead to early onset coronary artery heart disease by forming plaques in the bloodstream, which accumulate and restrict blood flow to the heart. This leads to angina chest pain and a greater risk of developing heart disease. The hardening of arteries can lead to heart disease, strokes and other vascular conditions. 

People with FH can also experience problems related to the buildup of cholesterol in other tissues. If cholesterol gathers in tendons it can cause growths known as tendon xanthomas. Individuals can also experience yellow deposits under the skin of the eyelids and grey circles on the cornea.

Heterozygous FH is the most common form, caused by a single DNA variant inherited from one parent.


A number of gene mutations have been identified as causative of FH. Mutations in LDLR, LDLRAP1, APOB, and PCSK9 genes cause FH, with LDLR mutations being the most common. 

LDLR is responsible for the production of the low-density lipoprotein receptor which binds to LDLs and removes them from the body, subsequently removing excess cholesterol. LDLR therefore plays a critical role in cholesterol regulation and mutations in the gene lead to higher levels of LDL.

The protein products of the LDLRAP1, APOB and PCSK9 genes are vital for the normal function of LDL receptors. Mutations in these genes lead to poorly functioning LDL receptors that fail to efficiently remove LDLs from the body. 

Mutations in LDLR, APOB and PCSK9 are inherited in an autosomal dominant pattern while mutations in LDLRAP1 are inherited in an autosomal recessive pattern.

Disease frequency:

Familial hypercholesterolemia is one of the most common genetic disorders affecting approximately 1 in 250 individuals.


The primary symptom of FH is increased blood cholesterol levels. Cholesterol levels over 190mg/dL in adults and 160mg/dL in adolescents is characteristic of FH. People with FH will often have a family history of heart disease or FH diagnosis. Individuals with FH will experience elevated levels of blood cholesterol from birth. 

Physical symptoms of FH can occur when cholesterol builds up in the body. These include lumps around knees, knuckles or elbows, swollen or painful Achilles tendons, yellowish skin around the eyes and a greyish circle in the eyes. 


Treatment of FH is focused on reducing LDL levels in the body. This can be achieved through specialised diet and exercise, medication, LDL apheresis and sometimes liver transplantation. 

A trans fat and saturated fat restricted diet can significantly reduce LDL levels in the body and reducing dietary cholesterol intake may also be effective.

Cholesterol-lowering medication such as atorvastatin, rosuvastatin or other statin-based drugs can be used to lower cholesterol levels in the body. 

In severe cases a process called LDL apheresis may be used whereby blood is drawn from the body via a catheter, LDLs are removed and the blood is returned to the body. 

In very rare and extreme cases a liver transplant may be used to treat FH.



HashtagFamilial Hypercholesterolemia, FH

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