Heterozygous vs Homozygous FH

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.

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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

Signs of Heterozygous FH

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 Family Heart 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.

6 Responses to “Heterozygous vs Homozygous FH”

  1. Kathy Giles

    I would like to know or learn more on Heterozygous , My has husband has lost 2 brothers to heart disease within 4 years. My husband also has heart disease, his sister has been diagnosed with Heterozygous, and is getting a pacemaker .

  2. Patricia Young

    I was I was so happy to find a website that addressed my rare blood disorder. I was told I may be one of the few people in their 60’s or older still leaving with this blood disorder. I am a Type IIa Homozygote FH person. I have 5 other siblings and I was the only homozygote. One brother has high cholesterol and one sister, everyone else is normal. I was diagnosed by Cook County Hospital in Chicago as a little girl but no one told me what was wrong with me. I had visible Xanthomas on both knees, elbows, back of my feet, small one under my fingers and a grey ring in my eyes. I became a ward of the state because I was the only child severely mistreated and constantly reminded of my physical appearance due to the Xanthomas. The child therapist recommended the removal of the Xanthomas and I had a bypass of the colon to reduce the lipid absorption which improved my outlook. I began to act and be treated very normal. I started college in 1973 but when my social worker dropped me without warning in 1976 I left college and joined the US Army after 21 years I had married, had a daughter (who is heterozygote) divorced, and medically from the service. In my 40’s I was diagnosed with Lupus and MS. I have been seen by NIH that loss funding for their research, John Hopkins diagnosed and treated my daughter and I off and on due to military moves and now I have a cardiologist that is clueless. I received LDL Apheresis for more than 25 years. I am now on repatha injections and weaned off the LDL Apheresis machine. I would love to share more about me and meet somebody like me as well. Please contact me I need to reestablish myself with up to date findings and research.

    • Amanda Sheldon

      Thanks for sharing your story Patricia. Someone will reach out to you soon or you can email us at info@familyheart.org. We also have a Homozygous Community (closed private group) on Facebook that you can join here: https://www.facebook.com/groups/842990089094178/about/

    • Jana Williams

      Hi, I was diagnosed at 8 years old with FH. My father was diagnosed in the 60’s, and passed at age 45. I’m one of six kids, we were all tested, I was the only one who has FH. I’ve have two daughters, both tested when they were 8 years old and was diagnosed with FH in the 80s. Our family has been on a low cholesterol diet all my life. I’ve tried all the statins, with no resolve. I believe exercise helps but does not effectively lower the numbers. At age 45 I had a triple bypass. I try to maintain a vegan diet but I also include my salmon and white fish too, so not really a vegan LOL. I just stumbled on to this website / support group. Some days are very discouraging. I’ve kind of felt alone until I read your story.

    • Binti

      Please email me I. Have the same problem like u.


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