Familial hypercholesterolemia, or FH, is an inherited genetic disorder that affects the body’s ability to manage cholesterol. The result is very high levels of LDL, or “bad” cholesterol, from birth. This protracted exposure to high levels of LDL leads to a twenty fold increase in the risk of premature cardiovascular disease. Only about 10% of people with FH have been diagnosed. Diagnosis is important because there are many available treatments and early aggressive treatment can lower your risk for heart disease or stroke.
Inheriting FH: Understanding Autosomal Dominance
The gene mutation that causes FH is autosomal dominant. This means that a parent with the disorder has a 50% chance of passing that gene to each of his or her children. If a child inherits the gene, because it is dominant, he or she will have the disorder. The term autosomal vs x-linked refers to the fact that the gene is not related to the sex chromosomes. It does not matter if it is the mother or the father who has the gene, or if the child is a girl or a boy.
Autosomal dominant disorders, like FH, tend to appear in each generation in a family. Because of this, people with FH have a family history of heart disease or stroke. However, if the child does not inherit the FH gene from his or her affected parent, he or she will not have the disorder and cannot pass it on to the next generation.
Heterozygous vs Homozygous FH
If you inherit the FH gene from one parent you will have heterozygous FH, meaning you have one FH gene and one normal gene. About 1 in 250 people around the world have heterozygous FH. Heterozygous FH is characterized by very high LDL cholesterol (above 190 for adults or above 160 for children) and a family history of high cholesterol, heart disease or stroke.
If both of your parents have FH and you inherit the FH gene from each of them, you will have homozygous FH, meaning you have two FH genes. Having two FH genes makes the disorder much more severe. Homozygous FH is very rare. Approximately 1 in one million people worldwide has homozygous FH. Homozygous FH is characterized by extremely high levels of LDL cholesterol and symptoms can be seen in childhood. Homozygous FH is much more difficult to treat adequately and people with homozygous FH can suffer from cardiac events even before the teen years.
Heterozygous FH: Signs, Symptoms and Treatment
People with FH have elevated cholesterol from birth. Cholesterol screening in children can identify people with probable FH based on an LDL-C level above 160 and a family history of heart disease. Cholesterol screening in adults can identify people with probable FH based on and LDL cholesterol level above 190 and a family history of heart disease. Many people with heterozygous FH do not exhibit any other symptoms. Only 10% of people with FH in the United States have been diagnosed, so some people do not learn that they have it until they suffer a coronary event such as myocardial infarction (MI) or sudden cardiac death. Some people will have signs of elevated cholesterol such as xanthomas (fatty deposits under the skin, often on the Achilles tendon or on the joints of the hand), xanthalasmas (fatty deposits under the skin on the eyelids) or corneal arcus (a grayish ring on the periphery of the cornea).
Lifestyle changes are the first line of treatment; however, for people with FH these changes rarely lower LDL levels adequately. There are several effective treatments for FH, including: statins, bile acid-sequestrants, ezetimibe, fibrates and nicotinic acid (niacin). A new class of drugs called PCSK9 inhibitors is currently in clinical trials. Each person is different, so it is important to work with your FH specialist to find the treatment that works best for you.
Homozygous FH: Signs, Symptoms and Treatment
The signs and symptoms of homozygous FH are the same as for heterozygous FH, however they appear earlier, often in early childhood, and the disease progresses much more aggressively. Cholesterol levels into the 700’s or even 1,000 require an early, aggressive and multi-pronged approach.
All of the treatments used for heterozygous FH are also used to treat homozygous FH. In addition, people with homozygous FH often undergo LDL apheresis, a process by which blood is removed through the patient’s vein and LDL is filtered out before the blood is passed back into a different vein, similar to dialysis. Some homozygous FH patients undergo a liver transplant in order to normalize LDL levels.
Early diagnosis and treatment of FH, including family screening to identify others who have inherited the disorder, are essential to reducing the risk of early cardiovascular disease. The FH Foundation’s mission is to raise awareness of FH through education, advocacy and research. For more information, sign up for our newsletter and consider donating today.