What is familial hypercholesterolemia?
Familial hypercholesterolemia is a hereditary condition, characterized by high total cholesterol levels and, specifically, elevated levels of low-density lipoprotein – otherwise known as LDLc or “bad” cholesterol. Cholesterol is a waxy fat that occurs naturally in the bodyand is found in all the body's cells. HDL and LDL are fat proteins known as lipoproteins, which play a role in the transport of cholesterol. When too much LDL cholesterol builds up, an individual is at risk of atherosclerosis and coronary heart conditions.
As the condition is genetic, it cannot be fully cured. However, it can be managed through a combination of lifestyle changes and medication.
Causes of familial hypercholesterolemia
Familial hypercholesterolemia is a genetic disorder caused by a mutated gene. This mutation disrupts the body’s ability to remove low-density lipoprotein from the blood as it normally would, resulting in the development of high levels of cholesterol.
The condition is autosomal dominant, meaning the gene mutation can be inherited if only one parent is a carrier. In these instances, the condition is known as heterozygous FH. In the rare case where both parents are carriers, a particularly severe variety of familial hypercholesterolemia known as homozygous FH will be passed on.
The condition is differentiated from standard hypercholesterolemia by its hereditary nature. Anyone can develop hypercholesterolemia – which is generally caused by unhealthy lifestyle choices – whereas only those with a family history of the condition can develop familial hypercholesterolemia. Standard high cholesterol generally develops in older individuals, whereas the genetic variety is present from birth and has a tendency to be more aggressive.
Signs and Symptoms of familial hypercholesterolemia
In many cases, especially in younger people, there will be no obvious symptoms of familial hypercholesterolemia. However, if signs or symptoms do present themselves, they may include:
- Xanthomas: Fatty deposits on the skin that typically appear on the hands, knees, buttocks, elbows and ankles.
- Xanthelasmas: Deposits of cholesterol around the eyelids.
- Arcus senilis: A white-colored ring around the cornea
- Arthralgia (joint pain)
- Tendonitis (inflamed tendons)
- History of unusual skin lesions
- At least one parent with severe hypercholesterolemia
The most significant consequence of familial hypercholesterolemia, however, is heart disease. In cases of heterozygous familial hypercholesterolemia, signs of atherosclerotic cardiovascular disease, such as angina and heart attack, will appear in middle age if the condition is not treated. In cases of homozygous hypercholesterolemia, symptoms occur in childhood, and many people with this condition die before the age of 20. Heart disease can lead to potentially life-threatening complications such as heart attack.
Diagnosing familial hypercholesterolemia
Diagnosing familial hypercholesterolemia will generally involve three stages: an examination of an individual’s medical history, a physical examination and blood tests.
As hypercholesterolemia is hereditary, doctors will first inquire about a person’s family medical history. This will particularly focus on the parents, who are the carriers of the disorder. In some cases, the genetic form of the condition may have been misdiagnosed as standard hypercholesterolemia or may not have been diagnosed at all, meaning that it is possible to be unknowingly at risk of contracting the genetic form of the condition.
Doctors will also carry out a full physical examination to help diagnose familial hypercholesterolemia. This will particularly focus on checking for fatty deposits on the skin and around the eyes – one of the more common exterior symptoms of high cholesterol levels. The doctor will also conduct a thorough cardiovascular examination.
Blood tests will be ordered to confirm a diagnosis of familial hypercholesterolemia. Blood tests will check for an individual’s total cholesterol level (HDL and LDL cholesterol) as well as the specific amount of LDL cholesterol.
Adults with the condition will normally have total cholesterol levels of around 300 milligrams per deciliter and over, whereas children will have levels of around 250 milligrams per deciliter and over. LDL cholesterol levels will typically be around 220 milligrams per deciliter and over in adults and around 170-200 milligrams per deciliter and over in children.
However, the exact levels involved will differ according to whether the condition is heterozygous or homozygous familial hypercholesterolemia. In heterozygous FH, LDLc levels are usually higher than 250mg/dL, around 290mg/dL to 300mg/dL, and increase with age. In people younger than 20 years of age, an LDLc level higher than 200mg/dL suggests heterozygous FH.
In homozygous FH, however, total cholesterol and LDLc levels higher than 600mg/dL are typical in both adults and children.
Genetic tests can also be used to determine the presence of the defective gene, and a test for fibroblasts (connective tissue cells) can allow doctors to see how the body is absorbing cholesterol.
Familial hypercholesterolemia treatment
Treatment for familial hypercholesterolemia aims to reduce the risk of heart disease or heart attack. It usually combines the use of:
- Medication:Statins (medicines which help lower the level of LDL in the blood) are typically prescribed to treat familial hypercholesterolemia. They are generally effective, but may be necessary throughout an individual’s life. Another medication, ezetimibe, may also be prescribed alongside statins if statins alone are ineffective. For patients with FH, particularly homozygous FH, treatment should ideally be managed by a lipid specialist. I
- Diet and lifestyle changes: Combating high cholesterol levels may also involve making healthy lifestyle choices, such as avoiding tobacco products, excessive amounts of alcohol and remaining physically active. Diet changes may also be necessary. This will focus on avoiding saturated fats present in foods, such as dairy products, meat and pastry. A vegetarian or even vegan lifestyle may be the best option for people with FH.
Familial hypercholesterolemia prognosis
The prognosis for familial hypercholesterolemia is dependent on how closely an individual follows the lifestyle and diet recommendations, as well as how well the body responds to the medication. These changes and medications can help significantly delay heart disease or heart attack.
Those with homozygous FH will generally receive a less positive prognosis, as will those who experience early complications, such as heart problems in childhood.
Heart UK. “Treatment for People with Familial Hypercholesterolemia (FH).” Accessed August 2, 2017. ↩