Genetics Northern California

Familial Hypercholesterolemia

There are two types of familial hypercholesterolemia (FH): Heterozygous FH and Homozygous FH.
Heterozygous FH is a common condition occurring in about 1 in 200 to 1 in 500 people, and is typically referred to as simply FH. The term “heterozygous” has to do with the number and types of genetic material (genes) inherited from parents—someone who is heterozygous for a particular condition means they’ve inherited one copy of gene with a change in it leading to a disorder (in this case, increased cholesterol) from one parent, and the other gene copy of the pair from the other parent is working normally. People with FH have less ability to digest cholesterol properly, leading to an accumulation in the blood. Total cholesterol may exceed 230 mg/dl and LDL (low density lipoprotein) cholesterol may exceed 160 mg/dl. FH is expected to be inherited in a dominant manner, meaning that there is a 50% chance for a parent to pass on the condition with each child.
Homozygous FH is a much more serious condition but is very rare, affecting only about one in a million people. “Homozygous” means that both copies of a gene linked to cholesterol are not working properly, inherited from each parent. The total cholesterol in homozygous FH is generally extremely elevated (600-1000 mg/dl). This situation can cause severe coronary artery disease occurring as early as the late teens, compared to 40’s to 60’s in other family members with one copy of a changed FH gene.

What age should children be tested?
Children should be tested by two years of age if a close family member (parent/grandparent/aunt/uncle) has a diagnosis of FH, extremely high LDL (over 200 mg/dL), and/or early cardiovascular disease (younger than 55 years old in men or younger than 65 years old in women)

Diagnosis - How to find out if you have FH
The diagnosis is made using a combination of family medical history and specific laboratory tests. These are the most commonly requested lipid tests:
• Cholesterol
• Triglycerides
• High Density Lipoprotein (HDL)
• Low Density Lipoprotein (LDL)
A 12 hour fast (nothing to eat or drink except plain water) is required before taking these blood tests.

Reference Range-Cholesterol.gif

Reference Range-Triglycerides

Reference Range-HDL Cholesterol.gif

Reference Range-LDL Cholesterol.gif

In children, adolescents and young adults (under 20 years), FH is suspected when the fasting level of LDL cholesterol is over 160 mg/dL or non-HDL cholesterol is over 190 mg/dL. These levels were established by studies of families known to have FH. 

Sometimes you can see physical signs of FH.
These could include one or more of the following (from the FH Foundation website):
    •  Bumps or lumps around the knuckles, elbows, and knees, which are called “xanthomas”. These are formed when excess cholesterol gets deposited on tendons or under the skin.
    • Yellowish areas around the eyes (“xanthelasmas”) or a white arc near the colored part of the eye (“corneal arcus”).
    • Swollen or painful Achilles tendons (“tendon xanthomas”). Excess cholesterol may deposit in the tendons, which makes them enlarged and may cause discomfort when wearing shoes.

GRD06d015The goal of treatment is to prevent early cardiovascular disease. Lipid-lowering medication is required to reach normal LDL levels. Treatment usually starts in late childhood and continues with lifetime medication. Healthy lifestyle choices improve the efficacy of the medication and decrease the dose needed. Healthy choices include:  

    • Choose low cholesterol and minimal saturated fat foods
        o High Cholesterol? Here’s What You Can Do
    • Avoid trans fats as much as possible
        o Click here to learn more about trans fats (American Heart Association webpage) 
    • Choose complex higher fiber foods over refined carbohydrate foods
        o Fiber Facts handout
        o Whole Grains and Fiber - American Heart Association webpage     
    • Focus on plant foods: The Plant Based Diet Booklet
    • Daily physical activity

Created by: Suzanne Kordesh, MPH, RD
Reviewed by: Dr. Leslie Manace Brenman, MD MPhil, Sub-Chief, Kaiser Permanente Northern California Genetics

Last Reviewed: January 2022