How Familial Hypercholesterolemia Is Diagnosed

Familial hypercholesterolemia (FH), or “pure hypercholesterolemia,” is an inherited condition that prevents the body from effectively getting rid of extra LDL (“bad”) cholesterol, increasing the risk of heart disease.

This article will review how a diagnosis of FH is usually made, which often includes a combination of taking a family history, blood tests, and doing a physical exam.

Self-Checks/At-Home Testing

One of the most important steps to take at home, whether FH is suspected or not, is to learn about your family’s health history. This is helpful for your overall health, but is also an important step in determining if you are at risk of FH.

FH is an inherited condition, meaning that to develop the condition, you must inherit a defective gene from at least one parent.

FH is also an autosomal dominant condition, which means that having just one gene for the disease will cause FH, even if the other gene is healthy. This is called heterozygous familial hypercholesterolemia (HeFH).

If two defective genes are inherited—one from each parent—the condition is called homozygous familial hypercholesterolemia (HoFH). This type is much more rare and presents with more severe symptoms.

If a person has FH, one of their biological parents always has it, too. In some cases, the parent with FH knows they have it, but FH symptoms are not always obvious and a family history of FH may not be confirmed. Only about 10% to 20% of people with FH are aware they have it.

If there is a family history of early heart disease or heart attacks (before age 55 in men and before age 65 in women), FH may be involved. A person with this family history should be screened by a healthcare provider, particularly if they also have high or borderline high LDL cholesterol levels.

Physical Examination

If FH is suspected, a healthcare provider may do a physical exam to look for symptoms and check the patient’s general health. Screening for FH may also be done by a primary healthcare provider as part of routine exams such as an annual physical.

A physical examination may involve:

• Asking about a personal and family history of heart disease and FH
• Asking about heart problems, high cholesterol, and other related symptoms and conditions in your personal or family history
• Performing a visual and tactile exam of the body, to look for signs such as fatty skin deposits
• Asking about and discussing other symptoms, such as chest pain or shortness of breath
• Answering questions the person has for the healthcare provider
• Making referrals to other healthcare providers or experts, or ordering tests if necessary
  

Labs and Tests

Blood Tests

Blood tests are run to check cholesterol levels, particularly LDL levels.

FH may be present if:

• Total cholesterol is found to be above 300 mg/dL (250 mg/dL in children)
• LDL is found to be above 200 mg/dL (150 mg/dL in children)

Less commonly than blood tests, other tests may be run, including the following.

Fibroblast Studies

Fibroblasts are found in connective tissue. They secrete collagen proteins that aid in maintaining a structural framework for many tissues, and they help with wound healing.

Fibroblasts are able to be isolated and can be grown in a laboratory, so they are helpful for genetic research.

Studies can be done on fibroblasts (which are usually taken from a small tissue sample of skin) to see how the body absorbs LDL cholesterol.

Genetic Testing

Genetic testing for FH involves looking for inherited genetic changes in three different genes (LDLR, APOB, and PCSK9) that have been identified as causing FH.

While genetic testing is successful in finding the mutation causing FH in about 60% to 80% of people thought to have FH, some mutations that cause FH are still not known. It is possible to have FH but not have it show in genetic testing. Confirming a mutation is not a requirement for diagnosing FH.

Genetic testing is usually done through a genetic counselor. This professional will discuss family history and the likelihood the person has FH. They will explain how the genetics of FH work. They will also have a conversation about if genetic testing is recommended, and the procedures to do so, if necessary.

Cascade Screening

Because FH is inherited, it is likely that if one person has it, other family members also have the condition. If FH is found in one family member, cascade screening may be performed.

Cascade screening means that when one person is diagnosed with FH, their immediate family members are also tested. This can help make an early diagnosis and start treatment before symptoms or complications arise.

Imaging

In children, non-invasive imaging procedures may be recommended. This may include a carotid intima-media thickness test (CIMT) to look for thickening of the carotid artery.

A 2014 study showed that carotid intima-media thickness is greater in children with FH than in their unaffected siblings by 8 years of age.

Differential Diagnoses

Most people with high cholesterol, even those with a family history of high cholesterol, do not have FH.

Most high cholesterol is caused by lifestyle habits like eating too many foods that contain saturated fat and not consuming enough fruits, vegetables, and whole grains.

FH is not caused by lifestyle choices and almost never resolves through healthy lifestyle habits alone. If high cholesterol is not lowered after lifestyle changes are made, a healthcare provider may screen for FH, make a referral to a genetic counselor, or make a referral to a lipid specialist.

One of the key factors to look for when determining if high cholesterol is caused by FH is the age of onset, both of the high cholesterol levels and the complications such as heart disease it can cause.

People with FH tend to experience these factors earlier in life than most, even as early as childhood. This is why when looking at a family history of heart problems and high cholesterol, acknowledging the ages it occurred is important.

All family history of cholesterol levels and heart health is important as indicators for predisposition to certain heart-related conditions. But if the heart problems occurred early, it could be an indication of FH, and it is a reason to have cholesterol checked from a young age.

A Word From Verywell

High cholesterol levels and a family history of early onset heart disease or heart attack may mean a person has FH—or it may not.

Most people with high cholesterol do not have FH. FH affects about one in 250 people, while lifestyle factors are responsible for most cases of high cholesterol.

Still, if you have risk factors for FH, it’s important to see your healthcare provider for screenings. If you have a family history of early onset heart problems or high cholesterol, it is worth getting your cholesterol levels checked and monitored regularly, even if you are young.

If you have high cholesterol, check in with your family members to see if there is a history of cholesterol or heart disease in your family.

If you receive notice that your cholesterol is high, make sure to go for follow-up tests and appointments. If lifestyle changes such as improved diet and exercise are not making a satisfactory improvement in your cholesterol levels, it’s possible FH is at play, and further treatment such as medication may be needed.