FH is caused by a mutation in the gene for the LDL
receptor, which is involved in LDL recycling. Mutations
in other genes that effect the process can cause inherited
high cholesterol that, though it isn’t FH, causes the same
problems. Those genes include the PCSK9 gene and the
gene for Apolipoprotein B.
• The LDL receptor sits on the surface of the liver and
binds to the cholesterol-containing lipoproteins and
pulls them out of the bloodstream.
• Apolipoprotein B is a little molecule that sits on the
outside of the cholesterol particle and binds to the
• PCSK9 is a naturally occurring enzyme that functions
to control how many LDL receptors
are on the surface of the liver.
All these genes are connected with
one another. If you inherit a specific
type of mutation in any of these three
genes, you can develop FH or inherited
Hetero and Homo
There are two types of FH —
heterozygous and homozygous.
Heterozygous FH is much more common
and occurs when a person inherits one
causal mutation from one parent. This
occurs in about 1 in 250 people.
Homozygous FH occurs when
someone inherits one causal mutation
from both parents. “This form is much
rarer,” Knowles said. These individuals
can have LDL cholesterol levels over
500 and many of them have bypass
surgeries or need them before they’re
adults. Left untreated, it is rare for these
patients to survive into their 20s.
Treatment is usually statin based. Because their
cholesterol levels are so high, FH patients often require
more than one medication, and sometimes more than
two. “If the response to statins is not adequate, additional
cholesterol lowering medications like ezetimibe are used,”
Knowles said. “People with extremely elevated LDL, like
those with the homozygous form, may undergo a dialysis-
like procedure, called LDL apheresis, every few weeks to
Another class of lipid-lowering medications (bile acid
sequestrants) like cholestyramine or colesevelam may also
be used. They reduce the amount of cholesterol absorbed
by the intestines, lowering the amount of cholesterol that
makes it into the blood.
“We say we never find an
individual with FH; we only
find families with FH.”
holesterol is a waxy
substance that comes from
two sources: your body and your
food. Your body, and especially your
liver, makes all the cholesterol you
need and circulates it through the
blood. But cholesterol is also found
in foods from animal sources, such
as meat, poultry and full-fat dairy
products. Your liver produces more
cholesterol when you eat a diet high
in saturated and trans fats.
Distinguishing the different types
of cholesterol can be confusing.
Here’s a primer:
• Serum cholesterol refers to the
total amount of cholesterol (both
LDL and HDL) in your blood.
• Dietary cholesterol refers to the
cholesterol that enters your body
through the food you eat.
• LDL (low-density lipoprotein)
cholesterol is called “bad”
cholesterol because it clogs
arteries in the process called
atherosclerosis. Diets high in
saturated fat and trans fat tend
to increase LDL levels. The lower
your LDL level the better.
• HDL (high-density lipoprotein)
cholesterol is known as “good”
cholesterol because it appears to
remove LDL cholesterol from your
tissues. The higher your HDL level