Diabetes and Lipid Clinic of Alaska



Familial Hypercholesterolemia

  • Autosomal Dominant Hypercholesterolemia (ADH) also known as Familial Hypercholesterolemia (FH) is one of the most frequent genetic metabolic diseases known.
  • Around 10 million people in the world are affected by FH. Close to 200,000 FH patients die each year due to cardiovascular complications related to elevated cholesterol levels.

In most ADH patients, there is excessive deposition of cholesterol in the arterial walls, leading to accelerated atherosclerosis and premature cardiovascular disease (CVD). Approximately 45% of male and 20% of female FH patients suffer from coronary artery disease (CAD) by the age of 50. FH leads to increased risk of myocardial infarction before age 40.

The underlying molecular defect causing FH consists of variations in the gene coding for the Low Density Lipoprotein Receptor (LDLR) protein and for FDB, in the gene coding for the Apolipoprotein B. Detection of these mutations/variations provides the only unequivocal confirmation of ADH. 

Effective treatments can lower cholesterol levels...
Patients with ADH have access to effective treatments that can lower cholesterol levels by up to 60%. This leads to the consequent decrease of cardiovascular risk and a significant increase in the life expectancy for those patients especially if treatment is begun early. However, only a minority of patients with ADH are diagnosed.

Early detection and treatment of ADH is critical...
Early detection and treatment of FH and FDB is critical to improving patient outcomes. Since ADH is a genetic based disease this means that on average half of the patients’ blood relatives, children, siblings and parents, are likely to have the disease. So if a patient is confirmed to have ADH then genetic testing of that patient’s family is recommended in order to detect new cases and start monitoring those without symptoms who may develop cardiovascular disease. Early detection and early treatment are the most important steps in helping to prevent the likely effects of hypercholesterolemia.

Both the World Health Organization and the American Heart Association recommend that genetic testing confirm a ADH diagnosis, as well as family screening (also known as cascaded testing) which can help identify other undiagnosed cases.

Frequently Asked Questions

Is a simple cholesterol test not enough for diagnosis?
Genetic testing is valuable because the genetic variations are permanent. results from the genetic testing can guide treatment and your adherence to the treatment. Moreover, it can help indicate if your children should be tested. Also LDLc levels can be masked by high levels of triglycerides or fibrinogen, which do not affect genetic testing.

Will ADH go away?
No. You will always have ADH which decreases your body's ability to remove cholesterol. So permanent treatment regimens and lifestyle modifications will be necessary to counter the progression of the disease.

How to know if my hypercholesterolemia could be caused by ADH?
several symptoms are typical of ADH, the presence or family history of tendon xanthomas (yellowish firm nodules in the skin), the presence or family history of elevated cholesterol in adults, and the presence or family history of early onset coronary heart disease. if you or someone in your family have one or more of these characteristics, talk to your physician about your risk.

If I have ADH will my children have it?
Maybe. ADH comes in two forms, heterozygous FH and the more severe homozygous ADH. If either parent has heterozygous ADH there is a 50% chance that their children will have the same condition. If both parents have heterozygous ADH there is an additional 25% chance that a child will have the more severe form of the disease, homozygous FH. Homozygous FH occurs in about 1 in a million births.

What happens if my children have genetically confirmed ADH?
Knowing at an early age that a child is affected is key to implement important lifestyle changes, including low cholesterol diet and exercise. This can delay the built up of cholesterol effects. Moreover studies have shown early treatment even in children has been very effective at combating the long term effects of hypercholesterolemia.

My father had coronary artery disease but I feel fine. Does this mean that I do not have ADH?
Cholesterol build up is cumulative and silent. If one of your parents has ADH there is a 50% chance you have it as well (higher if both your parents have FH). Genetic testing can help confirm the genetic basis and then guide testing of relevant family members, your children, your siblings and their children.

If I test negative for ADH does this mean I do not have ADH genetically?

No. Genetic testing looks for the most common causes of ADH which are genetic variations in the LDLR and APOB genes. However, as scientists study ADH they may identify new variants in genes not currently tested.

Do I have to get retested every few years?
No, just once. DNA make up stays constant throughout life.

Who is the "index" or "proband"?
This is a medical phrase that refers to the first patient to be tested and found to have the disease within a family.

Can I order this test from Progenika directly?
ADH genetic testing must be prescribed by your physician.If you are interested in genetic testing for FH, please contact the staff at Diabetes and Lipid Clinic of Alaska.

The information on this Web page is provided for educational purposes. You understand and agree that this information is not intended to be, and should not be used as, a substitute for medical treatment by a health care professional. You agree that Diabetes and Lipid Clinic of Alaska is not making a diagnosis of your condition or a recommendation about the course of treatment for your particular circumstances through the use of this Web page. You agree to be solely responsible for your use of information contained on this Web page

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