Familial Hypercholesterolemia (FH) is a genetic disease
that is related to the common disease hypercholesterolemia. Unlike 
hypercholesterolemia,
which is a non-genetic disease, patients suffering from familial hypercholesterolemia
have a much more serious condition than those people who have high levels
of cholesterol. These FH patients have a much higher chance of suffering
from heart attacks and stroke.
Hypercholesterolemia
describes the people with high levels of cholesterol.
In other words, the people who have too much cholesterol circulating in
their bloodstream. It is the result of the 
overproduction
and/or underutilization of Low-Density Lipoprotein
(LDL). It is known to be caused by the consumption of a high-cholesterol
diet and/or the genetic disease familial hypercholesterolemia (FH). Human
body usually produces about two-thirds of its needed cholesterol in the
liver, thus very little supplement of cholesterol is required. It is generally
believed that the typical high fat, high cholesterol, high protein, low
fiber U.S. diet is largely responsible for the unfortunate statistic of
600,000 deaths annually. Obesity and a sedentary life style add to the
risk. Cholesterol causes deposits to form inside blood vessels. The deposits
are formed through an oxidation interaction between the LDL and the free
radicals on the inside wall of the artery. These deposits are called plaque
and they cause atherosclerosis -blockages of blood flow- in the arteries.
If the blood flow is restricted or stopped in the arteries supplying the
heart, the result is a heart attack. If the blockage occurs in the arteries
supplying the brain, and causes brain tissue damage, the result is a stroke.
 Hypercholesterolemia
is a silent disease. No symptoms will occur until the resulting chest pain
of a heart attack or the symptoms of a stoke. |
Familial Hypercholesterolemia is a genetic disease that causes a major problem. It is a very common disease in humans. There is a mutation in the genetic encoding for the LDL receptors (LDLR gene) that are located on the surface of the liver cells. The function of these receptors is to pick up the circulating plasma LDL to be processed in the liver's cholesterol management. As the result of the lack of activity, the LDL particles are not recycled and are circulating in the bloodstream, a condition of hypercholesterolemia. Because FH occurs from many types of mutation on the LDL receptors, the frequency of this particular disease, especially in heterozygous patients, is very high.
Familial Hypercholesterolemia is an autosomal dominate disease which occurs about 1 in every 500 people. The homozygous FH is more rare, occuring with the frequency of about 1 in a million. The statistics for the homozygous FH is not surprising though, since patients suffering from two alleles of this gene usually do not survive pass their teens. The condition of hypercholesterolemia in FH patients are detectable at birth or shortly thereafter. The cholesterol levels in heterozygous patients are between350 to 500 mg/dL, and in homozygous, the levels are between 700 to 1,200 mg/dL (see NCEP table for comparison).
Tendon xanthomas commonly occur in FH patients. The heterozygous will develope these later in life, but the homozygous usually developes them in their childhood. Xanthomas are lesions caused by cholesterol deposits in various parts of the body. The common places are in the extensor tendons of the hands and eyelids (know as xanthelasmas).
Click here to view some pictures of xanthomas.
Curing homozygous patients is very difficult because they express little or no activity from the LDL receptor. They are resistant to most cholesterol-lowering drugs. Liver transplantation can provide the missing LDL receptors but requires special long-term followup cares for the transplanted organs, including continuous immunosuppression. FH homozygous are currently treated with modified forms of plasmapheresis that selectively remove Very Small Density Lipoprotein (VLDL) and Low Density Lipoprotein (LDL) from the plasma. The treatment must be done every one to three weeks depending on the clinical state of the patient. The heterozygous patients are generally treated in the same way as patients with hypercholesterolemia. However, they are usually advised to be treated with cholesterol-lowering drugs such as lovastatin, as well as a maintained diet of low fat and cholesterol intake at a younger age. Some physicians have advised their younger patients to adopt a drug therapy as soon as possible to prevent the progression of atherosclerosis. It is interesting to note that once a patient is treated with cholesterol-lowering drugs, they should remain on the drug therapy. Combinations of these agents can reduce the levels of serum cholesterol by 50 to 60%.
Also, the modern approach to this problem is gene therapy. It involves genetic transfers which consist of selective mechanism to deliver healthy genes and their promoter sequence for expression in the specifically targeted cell. The development of this strategy is on its way, and there had been some light seen at the other end of the tunnel. Gene therapy is expected to cure the homozygous FH patients and help remove the heterozygous patients from an early long-term drug therapy. It, however, does not provide a solution to cure the hypercholesterolemia patient suffering from high cholesterol levels resulting from high fat intake.
