Familial hypercholesterolemia

familial hypercholesterolaemiahypercholesterolemia, familialhereditary high cholesterolheterozygous familial and nonfamilialhomozygous familial hypercholesterolemia
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL, "bad cholesterol"), in the blood and early cardiovascular disease.wikipedia
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Genetic disorder

genetic diseasegenetic disordersgenetic diseases
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL, "bad cholesterol"), in the blood and early cardiovascular disease.

Statin

statinsHMG-CoA reductase inhibitorHMG-CoA reductase inhibitors
Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH (such as dietary modification and statin tablets).
In children statins are effective at reducing cholesterol levels in those with familial hypercholesterolemia.

LDL receptor

LDLRlow density lipoprotein receptorLDL-receptor
About 1 in 100 to 200 people have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare.
Michael S. Brown and Joseph L. Goldstein were awarded the 1985 Nobel Prize in Physiology or Medicine for their identification of LDL-R and its relation to cholesterol metabolism and familial hypercholesterolemia.

Apolipoprotein B

APOBapolipoprotein B-100apolipoprotein B-48
About 1 in 100 to 200 people have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare. In January 2013, The US FDA also approved mipomersen, which inhibits the action of the gene apolipoprotein B, for the treatment of homozygous familial hypercholesterolemia.
Mutations in gene APOB100 can also cause familial hypercholesterolemia, a hereditary (autosomal dominant) form of metabolic disorder Hypercholesterolemia.

LDL apheresis

Homozygous FH often does not respond to medical therapy and may require other treatments, including LDL apheresis (removal of LDL in a method similar to dialysis) and occasionally liver transplantation.
It is used in diseases featuring high LDL, such as the rare homozygous familial hypercholesterolemia, when the heterozygous form does not respond to medical treatment, or when the treatment has led to dangerous side-effects (such as rhabdomyolysis).

Genetic counseling

genetic counselorgenetic counsellinggenetic counsellor
New cases are generally offered genetic counseling.

Hypercholesterolemia

high cholesterolhigh blood cholesterolhypercholesterolaemia
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL, "bad cholesterol"), in the blood and early cardiovascular disease.
Elevated levels of non-HDL cholesterol and LDL in the blood may be a consequence of diet, obesity, inherited (genetic) diseases (such as LDL receptor mutations in familial hypercholesterolemia), or the presence of other diseases such as type 2 diabetes and an underactive thyroid.

Xanthoma

xanthomatosisXanthoma tuberosumEruptive xanthoma
Yellow deposits of cholesterol-rich fat may be seen in various places on the body such as around the eyelids (known as xanthelasma palpebrarum), the outer margin of the iris (known as arcus senilis corneae), and in the tendons of the hands, elbows, knees and feet, particularly the Achilles tendon (known as a tendon xanthoma).
Also associated with familial hypercholesterolemia (FH).

PCSK9

PCSK9 inhibitora series of discoveriesdrug that inhibits PCSK9
The most common genetic defects in FH are LDLR mutations (prevalence 1 in 500, depending on the population), ApoB mutations (prevalence 1 in 1000), PCSK9 mutations (less than 1 in 2500) and LDLRAP1. Alirocumab and evolocumab, both monoclonal antibodies against PCSK9, are specifically indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia, who require additional lowering of LDL cholesterol.
Meanwhile, a lab led by Catherine Boileau at the Necker-Enfants Malades Hospital in Paris had been following families with familial hypercholesterolaemia, a genetic condition that, in 90% of cases causes coronary artery disease (FRAMINGHAM study) and in 60% of cases may lead to an early death; they had identified a mutation on chromosome 1 carried by some of these families, but had been unable to identify the relevant gene.

Lipid-lowering agent

hypolipidemic agenthypolipidemicantihyperlipidemic
Heterozygous FH is normally treated with statins, bile acid sequestrants, or other lipid lowering agents that lower cholesterol levels.

Sitosterolemia

Phytosterolemiaphytosterolaemia
Sitosterolemia and cerebrotendineous xanthomatosis are two rare conditions that can also present with premature atherosclerosis and xanthomas.
Sitosterolemia may share several clinical characteristics with the well-characterized familial hypercholesterolemia (FH), such as the development of tendon xanthomas in the first 10 years of life and the development of premature atherosclerosis.

Achilles tendon

AchillesAchilles' tendoncalcaneal tendon
Yellow deposits of cholesterol-rich fat may be seen in various places on the body such as around the eyelids (known as xanthelasma palpebrarum), the outer margin of the iris (known as arcus senilis corneae), and in the tendons of the hands, elbows, knees and feet, particularly the Achilles tendon (known as a tendon xanthoma).
Tendon xanthomas are cholesterol deposits that commonly develop in the Achilles tendon of people with lipid metabolism disorders such as familial hypercholesterolemia.

Mipomersen

Kynamromipomersen sodium
In January 2013, The US FDA also approved mipomersen, which inhibits the action of the gene apolipoprotein B, for the treatment of homozygous familial hypercholesterolemia.
Mipomersen (INN; trade name Kynamro) is used to treat homozygous familial hypercholesterolemia and is administered by subcutaneous injection.

Alirocumab

Antibodies targeting PCSK9Praluent
Alirocumab and evolocumab, both monoclonal antibodies against PCSK9, are specifically indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia, who require additional lowering of LDL cholesterol.
Alirocumab is used as a second-line treatment to lower LDL cholesterol for adults who have a severe form of hereditary high cholesterol and people with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment have not worked.

Cholesterol

total cholesteroldietary cholesterolserum cholesterol
Cholesterol levels may be determined as part of health screening for health insurance or occupational health, when the external physical signs such as xanthelasma, xanthoma, arcus are noticed, symptoms of cardiovascular disease develop, or a family member has been found to have FH.

Lomitapide

Lomitapide, an inhibitor of the microsomal triglyceride transfer protein, was approved by the US FDA in December 2012 as an orphan drug for the treatment of homozygous familial hypercholesterolemia.
Lomitapide (INN, marketed as Juxtapid in the US and as Lojuxta in the EU) is a drug used as a lipid-lowering agent for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals.

Ezetimibe

Zetia
More controversial is the addition of ezetimibe, which inhibits cholesterol absorption in the gut.

Intima-media thickness

carotid intima-media thicknessthickened intima mediawall thickening
While it reduces LDL cholesterol, it does not appear to improve a marker of atherosclerosis called the intima-media thickness.
Carotid IMT has been used in many epidemiological and clinical studies and these have shown associations with several risk factors, including type 2 diabetes, familial hypercholesterolemia, high-density lipoprotein cholesterol (HDL-C), triglycerides, rheumatoid arthritis, non-alcoholic fatty liver disease, and air pollution.

Partial ileal bypass surgery

intestinal bypass surgery
Other surgical techniques include partial ileal bypass surgery, in which part of the small bowel is bypassed to decrease the absorption of nutrients and hence cholesterol, and portacaval shunt surgery, in which the portal vein is connected to the vena cava to allow blood with nutrients from the intestine to bypass the liver.
First introduced in 1962 by Professor Henry Buchwald of the University of Minnesota, the procedure is used to treat a number of hyperlipidemias including familial hypercholesterolemia.

Hyperlipidemia

hyperlipoproteinemiahyperlipidaemiaPrimary hyperlipoproteinemia
A pattern compatible with hyperlipoproteinemia type IIa on the Fredrickson classification is typically found: raised level of total cholesterol, markedly raised level of low-density lipoprotein (LDL), normal level of high-density lipoprotein (HDL), and normal level of triglycerides.

Michael Stuart Brown

Michael S. BrownMichael BrownMichael S Brown
In the early 1970s and 1980s, the genetic cause for FH was described by Dr Joseph L. Goldstein and Dr Michael S. Brown of Dallas, Texas.
The lack of sufficient LDL receptors is implicated in familial hypercholesterolemia, which predisposes heavily for cholesterol-related diseases.

Microsomal triglyceride transfer protein

MTTPMTPtriglyceride transfer protein
Lomitapide, an inhibitor of the microsomal triglyceride transfer protein, was approved by the US FDA in December 2012 as an orphan drug for the treatment of homozygous familial hypercholesterolemia.

Low-density lipoprotein

LDLLDL cholesterollow density lipoprotein
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL, "bad cholesterol"), in the blood and early cardiovascular disease.

Cardiovascular disease

heart diseasecardiac diseasecardiovascular
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL, "bad cholesterol"), in the blood and early cardiovascular disease.

Protein

proteinsproteinaceousstructural proteins
About 1 in 100 to 200 people have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare.