What is the Difference Between Heterozygous and Homozygous Familial Hypercholesterolemia?

Heterozygous and homozygous familial hypercholesterolemia (FH) are two forms of an inherited genetic disorder that causes high low-density lipoprotein (LDL) cholesterol levels, which can lead to heart disease, heart attack, or stroke if left untreated. The main differences between heterozygous and homozygous FH are:

1. Inheritance: Heterozygous FH occurs when an individual inherits the FH gene from only one parent, resulting in one FH gene and one normal gene. On the other hand, homozygous FH occurs when an individual inherits the FH gene from both parents, resulting in two FH genes.
2. Prevalence: Heterozygous FH is more common, affecting about 1 in 250 people worldwide. Homozygous FH is much rarer, affecting approximately 1 in one million people worldwide.
3. Cholesterol levels: Heterozygous FH is characterized by very high LDL cholesterol levels (above 190 for adults or above 160 for children). In contrast, homozygous FH is characterized by extremely high levels of LDL cholesterol, often reaching into the 700s or even 1,000.
4. Symptoms and progression: The signs and symptoms of homozygous FH are the same as for heterozygous FH, but they appear earlier, often in early childhood, and the disease progresses much more aggressively.
5. Treatment: Both heterozygous and homozygous FH are treated with cholesterol-lowering medications, such as statins. However, homozygous FH is much more difficult to treat adequately, and individuals with this form of the disorder often undergo LDL apheresis, an additional treatment to remove LDL cholesterol from the blood. In severe cases of homozygous FH, liver transplantation may be the only effective therapy.

Comparative Table: Heterozygous vs Homozygous Familial Hypercholesterolemia

Here is a table summarizing the differences between heterozygous and homozygous familial hypercholesterolemia (FH):

Heterozygous FH is characterized by very high LDL cholesterol levels and usually develops warning signs of heart disease later in life. On the other hand, homozygous FH is a more severe form of the disorder, with patients often showing signs of high cholesterol, including tendon xanthomas, in early childhood and potentially developing coronary heart disease during childhood. Both forms of FH are inherited in an autosomal dominant manner, meaning that if a child inherits the FH gene from one parent, they will have heterozygous FH, and if both parents have FH, there is a 25% chance that each child will inherit the disorder.