Materiały źródłowe

• #1 Familial hypercholesterolemia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/familial-hypercholesterolemia/symptoms-causes/syc-20353755

  Familial hypercholesterolemia is caused by a gene alteration that’s passed down from one or both parents. People who have this condition are born with it. This change prevents the body from ridding itself of the type of cholesterol that can build up in the arteries and cause heart disease. […] The risk of familial hypercholesterolemia is higher if one or both of your parents have the gene alteration that causes it. Most people who have the condition receive one affected gene. But in rare cases, a child can get the affected gene from both parents. This can cause a more severe form of the condition.

• #2 Familial hypercholesterolemia: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000392.htm

  Familial hypercholesterolemia is a genetic disorder. It is caused by a gene variant on chromosome 19. […] The defect makes the body unable to remove low density lipoprotein (LDL, or bad) cholesterol from the blood. This results in a high level of LDL in the blood. […] The condition is typically passed down through families in an autosomal dominant manner. That means you only need to get the abnormal gene from one parent in order to inherit the disease. […] In rare cases, a child may inherit the gene from both parents. When this occurs, the increase in cholesterol level is much more severe. The risk for heart attacks and heart disease are high, even in childhood.

• #3 Familial Hypercholesterolemia: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22067-familial-hypercholesterolemia

  Familial hypercholesterolemia, which you inherit, causes high LDL levels in your blood and raises your heart disease risk. […] Familial hypercholesterolemia is a genetic condition that causes high LDL, raising your risk of heart disease and stroke. […] FH is a genetic disorder you inherit or get from one or both of your biological parents. In most people with this genetic issue, a specific protein (LDL receptor) that gets LDL out of your blood doesn’t work well or there isn’t enough of it. […] Although most people with familial hypercholesterolemia will have a variant on one of three specific genes (APOB, LDLR or PCSK9), researchers are still discovering more. […] People with familial hypercholesterolemia have a much higher risk of atherosclerosis, which can cause heart attacks and strokes.

• #4 About Familial Hypercholesterolemia

  https://www.genome.gov/Genetic-Disorders/Familial-Hypercholesterolemia

  Familial hypercholesterolemia is an inherited condition that causes high levels of low density lipoprotein (LDL) cholesterol beginning at birth and heart attacks at an early age. […] Familial hypercholesterolemia is inherited in families in an autosomal dominant manner. In autosomal dominant inherited conditions, a parent who carries an altered gene that causes the condition has a 1 in 2 (50 percent) chance to pass on that altered gene to each of his or her children. […] The altered gene (gene mutation) that causes familial hypercholesterolemia is located on chromosome number 19. It contains the information for a protein called LDL receptor that is responsible to clear up LDL from the blood stream. […] One in 500 individuals carries one altered gene causing familial hypercholesterolemia.

• #5 Familial Hypercholesterolemia: Treatments, Symptoms, and More

  https://www.healthline.com/health/familial-hypercholesterolemia

  Familial hypercholesterolemia (FH) is a genetic disorder that causes high levels of LDL and total cholesterol in the blood, which can lead to heart disease at a young age. […] Familial hypercholesterolemia (FH) is an inherited condition that results in high levels of low-density lipoprotein (LDL) cholesterol. This also results in high total cholesterol as well and can lead to serious heart disease. […] FH is the most common inherited form of high cholesterol. […] FH is generally more severe than cases of nongenetic hypercholesterolemia. […] There are currently three known FH genes. Each is located on a different chromosome. In most cases, the condition results from inheriting one of the genes or pairs of genes. […] Researchers believe particular combinations of genetic material lead to the problem in some cases.

• #6 About Familial Hypercholesterolemia

  https://www.genome.gov/Genetic-Disorders/Familial-Hypercholesterolemia

  More rarely, a person inherits the gene mutation from both parents, making them genetically homozygous. Individuals who are homozygous have a much more severe form of hypercholesterolemia, with heart attack and death often occurring before age 30. […] Familial hypercholesterolemia is inherited in an autosomal dominant manner. This means that to have this condition, it is sufficient that the altered (mutated) gene is present on only one of the person’s two number 19 chromosomes. A person who inherits one copy of the gene mutation causing familial hypercholesterolemia from one of his/her parents is said to have heterozygous familial hypercholesterolemia. […] A person who inherits a mutated copy of the gene causing familial hypercholesterolemia from both parents is said to have homozygous familial hypercholesterolemia. This is a much more severe form of familial hypercholesterolemia than heterozygous familial hypercholesterolemia.

• #7 Familial Hypercholesterolemia: Treatments, Symptoms, and More

  https://www.healthline.com/health/familial-hypercholesterolemia

  FH is more common among certain ethnic or racial groups, such as those of Afrikaner, Ashkenazi Jewish, Finnish, French Canadian, or Lebanese descent. […] Identifying those with FH through genetic testing has allowed for early treatment. […] According to the American Heart Association, people with FH who are not treated and who have inherited the mutated gene from both parents, the most rare form, are at greatest risk for heart attack and death before age 30. […] Because FH is genetic, the best chance of preventing it is to seek genetic counseling before conceiving. […] Familial hypercholesterolemia (FH) is a genetic condition that causes high cholesterol levels. These high levels of cholesterol can lead to serious heart disease at a younger age than is typically seen with high cholesterol.

• #8 Familial Hypercholesterolemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556009/

  Familial hypercholesterolemia is a group of inherited genetic defects that lead to the severe elevation of serum cholesterol concentrations. […] The three main known genetic mutations in familial hypercholesterolemia are classified as defects in the LDL receptor (most common), apolipoprotein B (ApoB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Each of these three mutations leads to impairment of LDL receptors and a reduction in uptake of LDL cholesterol and subsequently causes high LDL cholesterol concentration. […] Over 1600 gene mutations in LDLR are detected in 85 to 90% of patients with familial hypercholesterolemia. APOB mutations accounting for about 10% of patients with familial hypercholesterolemia, and from this amount, the Arg3500Gln gene mutation is the most common cause. PCSK9 gene mutation causes less than 5% of patients with familial hypercholesterolemia. […] A defective LDL receptor is present at birth, but the longer patients live with extremely elevated LDLc levels, the higher their risk of CAD.

• #9 Familial hypercholesterolemia – Wikipedia

  https://en.wikipedia.org/wiki/Familial_hypercholesterolemia

  Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol (LDL cholesterol), in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly (abnormal trafficking). […] About 1 in 100 to 200 people have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from circulation, or the APOB gene that encodes apolipoprotein B (ApoB), the part of LDL particles that binds with LDL receptors. Mutations in other genes are rare but important to know, including gain-of-function mutations in the PCSK9 gene coding for the PCSK9 enzyme (which degrades LDL receptors), resulting in less LDL receptors available.

• #10 Familial Hypercholesterolemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556009/

  Familial hypercholesterolemia is a group of inherited genetic defects that lead to the severe elevation of serum cholesterol concentrations. […] The three main known genetic mutations in familial hypercholesterolemia are classified as defects in the LDL receptor (most common), apolipoprotein B (ApoB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Each of these three mutations leads to impairment of LDL receptors and a reduction in uptake of LDL cholesterol and subsequently causes high LDL cholesterol concentration. […] Over 1600 gene mutations in LDLR are detected in 85 to 90% of patients with familial hypercholesterolemia. APOB mutations accounting for about 10% of patients with familial hypercholesterolemia, and from this amount, the Arg3500Gln gene mutation is the most common cause. PCSK9 gene mutation causes less than 5% of patients with familial hypercholesterolemia. […] A defective LDL receptor is present at birth, but the longer patients live with extremely elevated LDLc levels, the higher their risk of CAD.

• #11 Familial hypercholesterolemia > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/familial-hypercholesterolemia

  Familial hypercholesterolemia (FH) is a genetic disorder that interferes with the body’s ability to process LDL cholesterol. […] A genetic mutation within one of four well-studied genes LDLR, LDLRAP1, APOB, or PCSK9 causes the disorder. The most frequent cause of FH is due to mutations found on the LDLR gene. These mutations affect production of certain proteins required for LDL particles to function properly. […] It’s possible that other, yet unknown genetic mutations influence the development of FH. […] FH is one of the more common genetic disorders in the U.S., affecting an estimated 1 in 250 people. […] If left untreated, the genetic condition can significantly increase a person’s risk of developing atherosclerosis (a buildup of plaque inside the arteries, which can lead to cardiovascular disease). […] If left untreated, FH can be a life-threatening disorder.

• #12 Familial Hypercholesterolemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556009/

  Familial hypercholesterolemia is a group of inherited genetic defects that lead to the severe elevation of serum cholesterol concentrations. […] The three main known genetic mutations in familial hypercholesterolemia are classified as defects in the LDL receptor (most common), apolipoprotein B (ApoB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Each of these three mutations leads to impairment of LDL receptors and a reduction in uptake of LDL cholesterol and subsequently causes high LDL cholesterol concentration. […] Over 1600 gene mutations in LDLR are detected in 85 to 90% of patients with familial hypercholesterolemia. APOB mutations accounting for about 10% of patients with familial hypercholesterolemia, and from this amount, the Arg3500Gln gene mutation is the most common cause. PCSK9 gene mutation causes less than 5% of patients with familial hypercholesterolemia. […] A defective LDL receptor is present at birth, but the longer patients live with extremely elevated LDLc levels, the higher their risk of CAD.

• #13 Familial hypercholesterolemia – Wikipedia

  https://en.wikipedia.org/wiki/Familial_hypercholesterolemia

  Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol (LDL cholesterol), in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly (abnormal trafficking). […] About 1 in 100 to 200 people have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from circulation, or the APOB gene that encodes apolipoprotein B (ApoB), the part of LDL particles that binds with LDL receptors. Mutations in other genes are rare but important to know, including gain-of-function mutations in the PCSK9 gene coding for the PCSK9 enzyme (which degrades LDL receptors), resulting in less LDL receptors available.

• #14 Mechanisms of Disease: genetic causes of familial hypercholesterolemia | Nature Reviews Cardiology

  https://www.nature.com/articles/ncpcardio0836

  Familial hypercholesterolemia (FH) is characterized by raised serum LDL cholesterol levels, which result in excess deposition of cholesterol in tissues, leading to accelerated atherosclerosis and increased risk of premature coronary heart disease. […] FH results from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, commonly caused by a loss-of-function mutation in the LDL-receptor gene (LDLR) or by a mutation in the gene encoding apolipoprotein B (APOB). […] FH is primarily an autosomal dominant disorder with a gene-dosage effect. […] An autosomal recessive form of FH caused by loss-of-function mutations in LDLRAP1, which encodes a protein required for clathrin-mediated internalization of the LDL receptor by liver cells, has also been documented. […] The most recent addition to the database of genes in which defects cause FH is one encoding a member of the proprotein convertase family, PCSK9.

• #15 Mechanisms of Disease: genetic causes of familial hypercholesterolemia | Nature Reviews Cardiology

  https://www.nature.com/articles/ncpcardio0836

  Rare dominant gain-of-function mutations in PCSK9 cosegregate with hypercholesterolemia, and one mutation is associated with a particularly severe FH phenotype. […] Not all patients with clinical FH have mutations in LDLR; mutations in APOB, PCSK9 and LDLRAP1 can affect LDL-receptor function in vivo.

• #16 Mechanisms of Disease: genetic causes of familial hypercholesterolemia | Nature Reviews Cardiology

  https://www.nature.com/articles/ncpcardio0836

  Familial hypercholesterolemia (FH) is characterized by raised serum LDL cholesterol levels, which result in excess deposition of cholesterol in tissues, leading to accelerated atherosclerosis and increased risk of premature coronary heart disease. […] FH results from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, commonly caused by a loss-of-function mutation in the LDL-receptor gene (LDLR) or by a mutation in the gene encoding apolipoprotein B (APOB). […] FH is primarily an autosomal dominant disorder with a gene-dosage effect. […] An autosomal recessive form of FH caused by loss-of-function mutations in LDLRAP1, which encodes a protein required for clathrin-mediated internalization of the LDL receptor by liver cells, has also been documented. […] The most recent addition to the database of genes in which defects cause FH is one encoding a member of the proprotein convertase family, PCSK9.

• #17 Familial hypercholesterolemia – Wikipedia

  https://en.wikipedia.org/wiki/Familial_hypercholesterolemia

  The most common genetic defects in FH are LDLR loss of function mutations (prevalence 1 in 250, depending on the population), APOB loss of function mutations (prevalence 1 in 1000), PCSK9 gain of function mutations (less than 1 in 2500) and LDLRAP1. […] Mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene were linked to autosomal dominant (i.e. requiring only one abnormal copy) FH in a 2003 report. […] Abnormalities in the ARH gene, also known as LDLRAP1, were first reported in a family in 1973. In contrast to the other causes, two abnormal copies of the gene are required for FH to develop (autosomal recessive).

• #18 Familial Hypercholesterolemia Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/121298-clinical

  A major change in the number or functional status of LDL receptors directly affects serum cholesterol levels. If the liver does not take up LDL particles, serum LDLc levels increase. Also, when LDL is not internalized by hepatocytes, hepatic synthesis of cholesterol is not suppressed. This leads to further cholesterol production despite high levels of circulating cholesterol. Therefore, circulating cholesterol levels are increased dramatically. The total and LDLc levels of infants and children with homozygous FH are higher than 600 mg/dL. In patients with heterozygous FH, half the LDL receptors are normal and half are rendered ineffective by the mutation. These patients’ total cholesterol and LDLc levels are twice as high as the population average. LDLc levels of 200-400 mg/dL are common. […] High levels of LDLc increase cholesterol uptake in nonhepatic cells that is independent of LDL receptors. These scavenger pathways allow cholesterol uptake by monocytes and macrophages, leading to foam cell formation, plaque deposition in the endothelium of coronary arteries, and premature CAD. Cholesterol also accumulates in other areas, particularly the skin, causing xanthelasmas and a variety of xanthomas. Early corneal arcus is frequent, and, in patients with the homozygous condition, valvular abnormalities, most frequently aortic stenosis, are common secondary to the deposition of cholesterol.

• #19 Homozygous Familial Hypercholesterolemia: Causes, Symptoms, and Treatment

  https://www.webmd.com/cholesterol-management/homozygous-familial-hypercholesterolemia

  Homozygous familial hypercholesterolemia is a disorder where it is hard for your body to remove LDL „bad” cholesterol from your blood. […] When you have homozygous familial hypercholesterolemia, you inherit two copies of a gene that isn’t working right, one from each of your parents. […] Normally, the liver removes extra LDL cholesterol from the blood using particles called LDL receptors. These receptors attach to LDL cholesterol and play a key role in keeping your cholesterol levels under control. When you have this disease, the faulty gene keeps the LDL receptors from working right. Your cholesterol levels get high. […] There’s no cure, so you’ll need to take drugs and follow a heart-healthy diet throughout your life. […] If different combinations of medicine aren’t doing the job, your doctor may also add injections of inclisiran (Leqvio) which has been approved as an add-on therapy to further lower (LDL-C). […] Sometimes, none of the treatments work. In that case, you might need a liver transplant. The new liver will have normal LDL receptors that will remove the bad cholesterol from your blood.

• #20 LDLR c.415G > A causes familial hypercholesterolemia by weakening LDLR binding to LDL | Lipids in Health and Disease | Full Text

  https://lipidworld.biomedcentral.com/articles/10.1186/s12944-024-02068-2

  Familial hypercholesterolemia (FH) is a prevalent hereditary disease that can cause aberrant cholesterol metabolism. […] In this study, we confirmed that c.415GA in low-density lipoprotein receptor (LDLR), an FH-related gene, is a pathogenic variant in FH by in silico analysis and functional experiments. […] It was estimated that the LDLRc.415GA variant in this family was likely pathogenic. […] Functional studies showed that this variant may lead to dyslipidemia by impairing the binding and absorption of LDLR to low-density lipoprotein (LDL). […] LDLR c.415GA is a pathogenic variant in FH; it causes a significant reduction in LDLRs capacity to bind LDL, resulting in impaired LDL uptake. […] The main pathogenic mechanism underlying FH is the incapacity of LDLR to remove LDL-C from the blood.

• #21 LDLR c.415G > A causes familial hypercholesterolemia by weakening LDLR binding to LDL | Lipids in Health and Disease | Full Text

  https://lipidworld.biomedcentral.com/articles/10.1186/s12944-024-02068-2

  Genetic variants in FH patients cause anomalies in the receptor endocytosis pathway, which abnormally raises plasma levels of LDL-C. […] Of the previously mentioned genetic variants, variants in the LDLR gene account for the bulk of FH instances. […] The present functional studies revealed that while this variant had no effect on protein synthesis, it dramatically lowered LDL absorption via impairing the ability of LDLR to bind LDL. […] It is hypothesized that this variant affects the uptake ability of LDLR, inhibiting the regular excretion of LDL-C in plasma and resulting in FH. […] LDLR variants can lead to FH by altering different stages of receptor-mediated endocytosis. […] In this family, both the proband and his son exhibited serious problems related to lipid metabolism, although genetic testing showed that they were heterozygous and cell tests demonstrated that the variant did not affect protein expression. […] LDLR c.415GA is a pathogenic variant in FH. It causes acidic amino acids to be replaced, greatly reducing the capacity of LDLR to bind to LDL. This prevents LDL-C from being taken up by cells and produces a noticeable LDL-C increase in plasma.

• #22 Primary hypercholesterolemia. Familial hypercholesterolemia

  https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=100787

  The main cause of FH is due to mutations in the LDLR gene, which codes for the LDL-c receptor, which is located on the plasma membrane of all cells, mainly that of hepatocytes. To date, more than 2000 variants distributed throughout the entire gene have been described, which could cause an alteration in the function or a decrease in the number of receptors to internalize LDL-c, what in turn causes raises in its serum concentration. […] The APOB gene encodes apolipoprotein B, which serves as a ligand between LDL-c and its receptor, which allows to internalize the lipoprotein inside the cell, to be metabolized. Therefore, mutations in this gene, even without defects in the receptors, also cause hypercholesterolemia. […] The PCSK9 gene encodes a protein that when it binds to the LDL receptor allows lysosomes to degrade it, so mutations that cause a „gain of function” generate an excessive production of the protein, decreasing in this way the number of receptors for LDL-c and consequently provoking hypercholesterolemia.

• #23 Primary hypercholesterolemia. Familial hypercholesterolemia

  https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=100787

  The main cause of FH is due to mutations in the LDLR gene, which codes for the LDL-c receptor, which is located on the plasma membrane of all cells, mainly that of hepatocytes. To date, more than 2000 variants distributed throughout the entire gene have been described, which could cause an alteration in the function or a decrease in the number of receptors to internalize LDL-c, what in turn causes raises in its serum concentration. […] The APOB gene encodes apolipoprotein B, which serves as a ligand between LDL-c and its receptor, which allows to internalize the lipoprotein inside the cell, to be metabolized. Therefore, mutations in this gene, even without defects in the receptors, also cause hypercholesterolemia. […] The PCSK9 gene encodes a protein that when it binds to the LDL receptor allows lysosomes to degrade it, so mutations that cause a „gain of function” generate an excessive production of the protein, decreasing in this way the number of receptors for LDL-c and consequently provoking hypercholesterolemia.

• #24 Familial Hypercholesterolemia Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/121298-clinical

  A major change in the number or functional status of LDL receptors directly affects serum cholesterol levels. If the liver does not take up LDL particles, serum LDLc levels increase. Also, when LDL is not internalized by hepatocytes, hepatic synthesis of cholesterol is not suppressed. This leads to further cholesterol production despite high levels of circulating cholesterol. Therefore, circulating cholesterol levels are increased dramatically. The total and LDLc levels of infants and children with homozygous FH are higher than 600 mg/dL. In patients with heterozygous FH, half the LDL receptors are normal and half are rendered ineffective by the mutation. These patients’ total cholesterol and LDLc levels are twice as high as the population average. LDLc levels of 200-400 mg/dL are common. […] High levels of LDLc increase cholesterol uptake in nonhepatic cells that is independent of LDL receptors. These scavenger pathways allow cholesterol uptake by monocytes and macrophages, leading to foam cell formation, plaque deposition in the endothelium of coronary arteries, and premature CAD. Cholesterol also accumulates in other areas, particularly the skin, causing xanthelasmas and a variety of xanthomas. Early corneal arcus is frequent, and, in patients with the homozygous condition, valvular abnormalities, most frequently aortic stenosis, are common secondary to the deposition of cholesterol.

• #25 Primary hypercholesterolemia. Familial hypercholesterolemia

  https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=100787

  Of the primary, due to pure or predominant genetic causes, the most common is familial hypercholesterolemia (FH) (OMIM 143890), a disease with an autosomal dominant inheritance pattern, characterized by the fact that affected patients have very high blood cholesterol levels from birth, accelerated atherosclerosis, and thus a very high risk of premature death from CVD. […] FH is caused by mutations in the LDLR (19p13.2), APOB (2p24.1) and/or PCSK9 (1p32.3) genes. These genes code for proteins that participate in the metabolism of low-density lipoprotein cholesterol (LDL-c), for which mutations in any of the three alter their homeostasis, causing an increase in serum concentration, a rise in cholesterol deposits in some tissues, and the development of atherosclerotic lesions, in turn responsible for cardiovascular syndromes.

• #26 Familial Hypercholesterolemia | What We Do | World Heart Federation

  https://world-heart-federation.org/what-we-do/cholesterol/familial-hypercholesterolemia/

  Familial hypercholesterolemia (FH) is a genetic condition that causes high cholesterol. […] Familial hypercholesterolemia is an inherited, metabolic disorder found in all races and ethnicities. […] Individuals with FH have high levels of low-density lipoprotein (LDL) cholesterol, sometimes called bad cholesterol, due to a mutation in one of several genes responsible for the regulation and elimination of cholesterol. […] Children of people with FH have an at least 50% chance of inheriting it. […] Individuals who inherited one mutation develop heterozygous familial hypercholesterolemia (HeFH), the most common form of FH. In contrast, individuals who inherited two abnormal mutations develop homozygous familial hypercholesterolemia (HoFH), a particularly rare and life-threatening form of FH, characterized by extreme levels of blood cholesterol.

• #27 Familial Hypercholesterolemia – Family Heart Foundation

  https://familyheart.org/familial-hypercholesterolemia

  Familial hypercholesterolemia (FH) is a common life-threatening genetic condition that causes high cholesterol. […] This happens because a genetic mutation affects the way cholesterol is cleared by the body. […] Like many other genetic conditions, FH is inherited. […] If you have FH, every child you have has a 50% chance of inheriting FH. […] Most people with FH have mutations in one of three genes: LDLR gene, APOB gene, and PCSK9 gene. […] One Inherited Mutation results in heterozygous familial hypercholesterolemia (HeFH). This occurs when one mutation is passed down to a child, typically from one parent. […] Two Inherited Mutations When the mutation for HeFH is passed on from both parents to their children this can result in homozygous familial hypercholesterolemia (HoFH), the more rare and severe form of FH.

• #28 Familial Hypercholesterolemia Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/121298-clinical

  A major change in the number or functional status of LDL receptors directly affects serum cholesterol levels. If the liver does not take up LDL particles, serum LDLc levels increase. Also, when LDL is not internalized by hepatocytes, hepatic synthesis of cholesterol is not suppressed. This leads to further cholesterol production despite high levels of circulating cholesterol. Therefore, circulating cholesterol levels are increased dramatically. The total and LDLc levels of infants and children with homozygous FH are higher than 600 mg/dL. In patients with heterozygous FH, half the LDL receptors are normal and half are rendered ineffective by the mutation. These patients’ total cholesterol and LDLc levels are twice as high as the population average. LDLc levels of 200-400 mg/dL are common. […] High levels of LDLc increase cholesterol uptake in nonhepatic cells that is independent of LDL receptors. These scavenger pathways allow cholesterol uptake by monocytes and macrophages, leading to foam cell formation, plaque deposition in the endothelium of coronary arteries, and premature CAD. Cholesterol also accumulates in other areas, particularly the skin, causing xanthelasmas and a variety of xanthomas. Early corneal arcus is frequent, and, in patients with the homozygous condition, valvular abnormalities, most frequently aortic stenosis, are common secondary to the deposition of cholesterol.

• #29 Familial Hypercholesterolemia | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/f/familial-hypercholesterolemia.html

  Familial hypercholesterolemia is an inherited genetic condition that is present from birth (congenital) and causes high levels of low density lipoprotein (LDL), sometimes known as „bad cholesterol.” […] These high levels of LDL cholesterol occur due to a genetic mutation that prevents the body from removing LDL cholesterol from the blood. […] Familial hypercholesterolemia is most often caused by a defect in 3 different genes (LDL-receptor gene, PCSK 9 gene and Apo B gene). […] Those with a partial genetic defect (Heterozygous FH or HeFH) typically experience heart attacks between the ages of 40 and 50 years of age (men) or between 50 and 60 years of age (women). […] Those with a complete genetic defect (homozygous FH or HoFH) can actually have heart attacks in their teens or twenties.

• #30 Homozygous Familial Hypercholesterolemia: Causes, Symptoms, and Treatment

  https://www.webmd.com/cholesterol-management/homozygous-familial-hypercholesterolemia

  Homozygous familial hypercholesterolemia is a disorder where it is hard for your body to remove LDL „bad” cholesterol from your blood. […] When you have homozygous familial hypercholesterolemia, you inherit two copies of a gene that isn’t working right, one from each of your parents. […] Normally, the liver removes extra LDL cholesterol from the blood using particles called LDL receptors. These receptors attach to LDL cholesterol and play a key role in keeping your cholesterol levels under control. When you have this disease, the faulty gene keeps the LDL receptors from working right. Your cholesterol levels get high. […] There’s no cure, so you’ll need to take drugs and follow a heart-healthy diet throughout your life. […] If different combinations of medicine aren’t doing the job, your doctor may also add injections of inclisiran (Leqvio) which has been approved as an add-on therapy to further lower (LDL-C). […] Sometimes, none of the treatments work. In that case, you might need a liver transplant. The new liver will have normal LDL receptors that will remove the bad cholesterol from your blood.

• #31 Familial Hypercholesterolemia | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/f/familial-hypercholesterolemia.html

  Familial hypercholesterolemia is an inherited genetic condition that is present from birth (congenital) and causes high levels of low density lipoprotein (LDL), sometimes known as „bad cholesterol.” […] These high levels of LDL cholesterol occur due to a genetic mutation that prevents the body from removing LDL cholesterol from the blood. […] Familial hypercholesterolemia is most often caused by a defect in 3 different genes (LDL-receptor gene, PCSK 9 gene and Apo B gene). […] Those with a partial genetic defect (Heterozygous FH or HeFH) typically experience heart attacks between the ages of 40 and 50 years of age (men) or between 50 and 60 years of age (women). […] Those with a complete genetic defect (homozygous FH or HoFH) can actually have heart attacks in their teens or twenties.

• #32 Familial Hypercholesterolemia: Screening, Diagnosis, and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2024/0900/editorial-hypercholesterolemia.html

  Familial hypercholesterolemia, an autosomal dominant genetic disorder, is characterized by markedly increased low-density lipoprotein (LDL) cholesterol that causes premature arteriosclerotic cardiovascular disease (ASCVD). […] Homozygous familial hypercholesterolemia typically presents with pathognomonic physical findings such as xanthomas or a corneal arcus. In contrast, heterozygous familial hypercholesterolemia is not indicated by clinical findings and is typically not diagnosed until after an early-onset ASCVD event (younger than 50 years). […] The worldwide prevalence of heterozygous familial hypercholesterolemia is estimated to be 1 in 250 to 350, and ASCVD events can occur with this condition as young as 17 years in men and by 25 years of age in women. […] The Dutch Criteria for Familial Hypercholesterolemia is a validated tool to assist clinicians in screening decisions and diagnosis.

• #33 Current causes of death in familial hypercholesterolemia | Lipids in Health and Disease | Full Text

  https://lipidworld.biomedcentral.com/articles/10.1186/s12944-022-01671-5

  CVD mortality in heFH individuals is lower and occurs later than that described in the last century but is still higher than that in non-FH individuals. […] This improved prognosis of CVD risk is not associated with changes in non-CVD mortality. […] The genetic characterization of FH in recent years has demonstrated that the heFH phenotype is more heterogeneous than previously believed, including the presence of CVD. […] This study also analysed non-CVD mortality in these genetically defined heFH families with a large history of lipid-lowering drug consumption for two purposes: first, to check whether lipid-lowering therapy could play a role in other comorbidities, and second, to explore whether the FH-causing mutation itself might be associated with morbidities other than CVD once heFH subjects live long enough without CVD, something that, until now, would have been hidden by early mortality. […] In conclusion, these results show that current CVD mortality in heFH patients is lower and occurs later than that described in the last century but is still higher than that in non-FH patients.

• #34 Familial Hypercholesterolemia (FH): Diagnosis, Genetics

  https://heartcare.sydney/familial-hypercholesterolemia/

  Familial hypercholesterolemia (FH) is a genetic disorder that causes high levels of low-density lipoprotein (LDL) cholesterol, also known as bad cholesterol, in the blood. People with FH have a mutation in one of three genes that control cholesterol metabolism, resulting in excessive production or impaired removal of LDL by the liver. […] In most cases of FH, mutations in the LDL receptor gene cause the disorder. However, mutations in the APo-B and PCSK9 genes can also lead to FH, but less commonly. […] The LDL receptor, located on cell surfaces, including liver cells, binds to LDL particles that transport cholesterol and lipids in the bloodstream. This binding allows cells to use LDL particles for energy or other purposes like hormone production. […] In individuals with FH, mutations in the LDL receptor gene can decrease the number or impair the function of the receptors. This reduction in the binding and clearance of LDL particles leads to the accumulation of LDL cholesterol in the bloodstream and an increased risk of atherosclerotic heart disease.

• #35 The latest thinking on inherited high cholesterol – Harvard Health

  https://www.health.harvard.edu/heart-health/the-latest-thinking-on-inherited-high-cholesterol

  Familial hypercholesterolemia a common cause of early heart attacks can cause very high LDL cholesterol levels. […] Within this group, an important minority has familial hypercholesterolemia (FH), a genetic condition that affects about one in 250 adults. […] Most people with FH have a mutation or variant in one of three different genes that provide instructions that help remove excess LDL from the bloodstream. […] People who inherit one variant from a parent have heterozygous FH, which can cause LDL levels as high as 350 milligrams per deciliter (mg/dL). […] People who inherit two variants (one from each parent) have homozygous FH. […] This very rare condition, which affects only about four in a million people, can lead to LDL levels as high as 1,000 mg/dL. […] But the biggest threat is the buildup of LDL in the arteries supplying the heart.

• #36 NHS England — London » Familial Hypercholesterolemia (FH)

  https://www.england.nhs.uk/london/london-clinical-networks/our-networks/cardiac/familial-hypercholesterolaemia/

  Familial Hypercholesterolemia (FH) is a genetic disease which results in the reduced clearance of atherogenic LDL-cholesterol (bad cholesterol) in the blood, and an increased risk of early heart disease. […] FH is usually caused by mutations in the low-density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and one particular mutation in the APOE gene (whose prevalence is currently unknown). […] In a landmark study the UCL group showed that in the vast majority of the no-mutation patients the cause of their hypercholesterolemia is polygenic and not due to a single unknown gene.

• #37 Familial Hypercholesterolemia: Treatments, Symptoms, and More

  https://www.healthline.com/health/familial-hypercholesterolemia

  FH is more common among certain ethnic or racial groups, such as those of Afrikaner, Ashkenazi Jewish, Finnish, French Canadian, or Lebanese descent. […] Identifying those with FH through genetic testing has allowed for early treatment. […] According to the American Heart Association, people with FH who are not treated and who have inherited the mutated gene from both parents, the most rare form, are at greatest risk for heart attack and death before age 30. […] Because FH is genetic, the best chance of preventing it is to seek genetic counseling before conceiving. […] Familial hypercholesterolemia (FH) is a genetic condition that causes high cholesterol levels. These high levels of cholesterol can lead to serious heart disease at a younger age than is typically seen with high cholesterol.

• #38 Familial hypercholesterolaemia: A guide for general practice

  https://www1.racgp.org.au/ajgp/2019/september/familial-hypercholesterolaemia

  FH is a common, hereditary, autosomal dominant disorder of lipid metabolism. […] FH should always be considered in adults with a total cholesterol level of 7.5 mmol/L or a low-density lipoprotein cholesterol (LDL-C) level of 5.0 mmol/L, especially if there is a personal or family history of premature coronary heart disease (CHD). […] The DLCNS is based on several key factors including the patients family history of premature cardiovascular disease (CVD), their personal CVD history, their untreated LDL-C levels and physical stigmata such as tendon xanthomas or arcus cornealis. […] A negative genetic test does not exclude FH because more than 2000 mutations of LDLR exist. […] Patients with a DLCNS 6 should be advised they have a phenotypic diagnosis of FH. […] Because FH is hereditary, dietary and lifestyle measures alone are not sufficient to manage the condition; however, lifestyle modification may be helpful, especially avoidance of smoking.

• #39 Familial hypercholesterolemia – Wikipedia

  https://en.wikipedia.org/wiki/Familial_hypercholesterolemia

  Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol (LDL cholesterol), in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly (abnormal trafficking). […] About 1 in 100 to 200 people have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from circulation, or the APOB gene that encodes apolipoprotein B (ApoB), the part of LDL particles that binds with LDL receptors. Mutations in other genes are rare but important to know, including gain-of-function mutations in the PCSK9 gene coding for the PCSK9 enzyme (which degrades LDL receptors), resulting in less LDL receptors available.

• #40 What is FH | Canadian Heart Patient Alliance

  https://www.heartpatientalliance.ca/general-information/types-of-cardiovascular-disease/what-is-fh/

  FH is short for Familial Hypercholesterolemia. It is an inherited disorder. […] This means it is passed down through families by altered genes, called genetic mutations or gene alterations. […] The cause is a faulty gene (called a genetic mutation) that makes the liver not able to remove (metabolize) excess bad cholesterol called low-density lipoprotein cholesterol or LDL-C, for short. […] FH is not caused by diet or lifestyle. […] Individuals with FH are unable to recycle this natural supply of cholesterol that their bodies are constantly producing. […] FH begins at birth and if is left untreated can cause severe cardiovascular events such as heart attacks, strokes and even narrowing of the heart valves at early age. […] FH is an inherited condition, which means it can be passed from parents to their children.

• #41 Familial hypercholesterolaemia: A guide for general practice

  https://www1.racgp.org.au/ajgp/2019/september/familial-hypercholesterolaemia

  It may be helpful to offer patients an open door policy to consider your advice and return at any time. […] FH results in very high levels of LDL-C from birth. […] If untreated, this cholesterol burden remains throughout life, accelerating premature CVD, especially myocardial infarction and angina, by 34 decades. […] Diagnosis of FH in children ideally occurs before the age of 10 years. […] However, diagnosis may need to occur by three years of age if both parents have FH and the risk of homozygous FH exists. […] Because FH is a hereditary, lifelong condition likely to result in premature CHD or death unless properly managed, affected patients should have care plans developed to maximise best practice approach to treatment. […] The cholesterol burden present from birth accelerates the onset of CVD. […] Diet and lifestyle modifications alone are not sufficient for management. […] Greater awareness of FH by health professionals and the public is needed.

• #42 Familial Hypercholesterolemia: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22067-familial-hypercholesterolemia

  Without treatment, people who have FH have 20 times the risk of coronary artery disease compared to someone without the disease. […] Since FH is a condition you inherit from your parents, it’s a part of your DNA all your life. You’ll need lifelong treatment. […] Healthcare providers don’t have a cure for familial hypercholesterolemia. But once you know you have FH, your provider can treat you for it and help you prevent cardiovascular disease. […] Getting treatment for familial hypercholesterolemia cuts down your risk of heart disease by more than half.

• #43 Familial Hypercholesterolemia | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/f/familial-hypercholesterolemia.html

  Familial hypercholesterolemia is an inherited genetic condition that is present from birth (congenital) and causes high levels of low density lipoprotein (LDL), sometimes known as „bad cholesterol.” […] These high levels of LDL cholesterol occur due to a genetic mutation that prevents the body from removing LDL cholesterol from the blood. […] Familial hypercholesterolemia is most often caused by a defect in 3 different genes (LDL-receptor gene, PCSK 9 gene and Apo B gene). […] Those with a partial genetic defect (Heterozygous FH or HeFH) typically experience heart attacks between the ages of 40 and 50 years of age (men) or between 50 and 60 years of age (women). […] Those with a complete genetic defect (homozygous FH or HoFH) can actually have heart attacks in their teens or twenties.

• #44 Pure hypercholesterolemia: Causes, symptoms, and treatment

  https://www.medicalnewstoday.com/articles/316173

  A parent with FH has a 50% chance of passing the condition on to a child. […] If a person inherits the mutated genes that cause FH from both parents, they are more likely to develop xanthomas at an early age and even in infancy. […] According to the National Human Genome Research Institute, men with FH tend to have heart attacks early in life, when they are in their 40s and 50s. […] If a person inherits mutated genes for FH from both parents, their risk of heart attack and death before 30 years of age substantially increases. […] Most people inherit the mutated gene that causes FH from one parent. If a person inherits it from both, they have a high risk of developing severe complications. […] There is no way to prevent FH. If a parent has the mutated gene, you can still get HeFH.

• #45 9 Things You Need to Know About Inherited High Cholesterol

  https://www.everydayhealth.com/high-cholesterol/treatment/10-things-you-need-to-know-about-inherited-high-cholesterol/

  If left undiagnosed and untreated, people with FH have a 20 times greater risk of developing heart disease, according to the American Heart Association. […] Patients are also susceptible to peripheral vascular disease and stroke much earlier than the general population. […] While a healthy lifestyle cannot fix familial hypercholesterolemia alone, it is still strongly encouraged. […] Statin medications are another layer of treatment for FH. […] A study in the July 2018 Frontiers in Pharmacology identified 14 treatment options for FH ranging from diet to fish oils to genetic therapy. […] Often, medical treatment is a last resort for children with any condition. But for FH, the earlier treatment happens, the better. […] A review published in the Journal of the American Heart Association found that universal lipid screening is recommended in children as early as age 2 for families with a history of high cholesterol and screenings around ages 9 to 11 for everyone else. […] Underberg says early diagnosis and treatment are akin to getting a car to a mechanic right away instead of waiting for it to break down.

• #46 Familial Hypercholesterolemia Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/121298-clinical

  A major change in the number or functional status of LDL receptors directly affects serum cholesterol levels. If the liver does not take up LDL particles, serum LDLc levels increase. Also, when LDL is not internalized by hepatocytes, hepatic synthesis of cholesterol is not suppressed. This leads to further cholesterol production despite high levels of circulating cholesterol. Therefore, circulating cholesterol levels are increased dramatically. The total and LDLc levels of infants and children with homozygous FH are higher than 600 mg/dL. In patients with heterozygous FH, half the LDL receptors are normal and half are rendered ineffective by the mutation. These patients’ total cholesterol and LDLc levels are twice as high as the population average. LDLc levels of 200-400 mg/dL are common. […] High levels of LDLc increase cholesterol uptake in nonhepatic cells that is independent of LDL receptors. These scavenger pathways allow cholesterol uptake by monocytes and macrophages, leading to foam cell formation, plaque deposition in the endothelium of coronary arteries, and premature CAD. Cholesterol also accumulates in other areas, particularly the skin, causing xanthelasmas and a variety of xanthomas. Early corneal arcus is frequent, and, in patients with the homozygous condition, valvular abnormalities, most frequently aortic stenosis, are common secondary to the deposition of cholesterol.

• #47 Familial Hypercholesterolemia Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/121298-clinical

  A major change in the number or functional status of LDL receptors directly affects serum cholesterol levels. If the liver does not take up LDL particles, serum LDLc levels increase. Also, when LDL is not internalized by hepatocytes, hepatic synthesis of cholesterol is not suppressed. This leads to further cholesterol production despite high levels of circulating cholesterol. Therefore, circulating cholesterol levels are increased dramatically. The total and LDLc levels of infants and children with homozygous FH are higher than 600 mg/dL. In patients with heterozygous FH, half the LDL receptors are normal and half are rendered ineffective by the mutation. These patients’ total cholesterol and LDLc levels are twice as high as the population average. LDLc levels of 200-400 mg/dL are common. […] High levels of LDLc increase cholesterol uptake in nonhepatic cells that is independent of LDL receptors. These scavenger pathways allow cholesterol uptake by monocytes and macrophages, leading to foam cell formation, plaque deposition in the endothelium of coronary arteries, and premature CAD. Cholesterol also accumulates in other areas, particularly the skin, causing xanthelasmas and a variety of xanthomas. Early corneal arcus is frequent, and, in patients with the homozygous condition, valvular abnormalities, most frequently aortic stenosis, are common secondary to the deposition of cholesterol.

• #48 Familial hypercholesterolemia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia/

  Familial hypercholesterolemia is an inherited condition characterized by very high levels of cholesterol in the blood. […] Mutations in the APOB, LDLR, LDLRAP1, or PCSK9 gene cause familial hypercholesterolemia. Changes in the LDLR gene are the most common cause of this condition. […] Less commonly, familial hypercholesterolemia is caused by mutations in the APOB, LDLRAP1, or PCSK9 gene. […] Both genetic and environmental risk factors play roles in familial hypercholesterolemia. […] Familial hypercholesterolemia accounts for only a small percentage of all cases of high cholesterol.

• #49 Familial hypercholesterolaemia: A guide for general practice

  https://www1.racgp.org.au/ajgp/2019/september/familial-hypercholesterolaemia

  It may be helpful to offer patients an open door policy to consider your advice and return at any time. […] FH results in very high levels of LDL-C from birth. […] If untreated, this cholesterol burden remains throughout life, accelerating premature CVD, especially myocardial infarction and angina, by 34 decades. […] Diagnosis of FH in children ideally occurs before the age of 10 years. […] However, diagnosis may need to occur by three years of age if both parents have FH and the risk of homozygous FH exists. […] Because FH is a hereditary, lifelong condition likely to result in premature CHD or death unless properly managed, affected patients should have care plans developed to maximise best practice approach to treatment. […] The cholesterol burden present from birth accelerates the onset of CVD. […] Diet and lifestyle modifications alone are not sufficient for management. […] Greater awareness of FH by health professionals and the public is needed.

• #50 Familial Hypercholesterolemia | What We Do | World Heart Federation

  https://world-heart-federation.org/what-we-do/cholesterol/familial-hypercholesterolemia/

  FH is inherited. Typically, parents with one pathogenic mutation have a 50% chance of passing down the condition to each child. […] FH is severely underdiagnosed. Today, only 10% of individuals born with FH have been diagnosed worldwide. […] Early diagnosis and lifelong treatment of FH reduces the risk of premature cardiovascular disease and heart attacks. […] Individuals with FH can live longer and healthier lives if treatment begins early in life. […] In the case of FH, lifestyle and diet interventions are not enough. Patients will always require cholesterol-lowering therapies. […] FH drug treatment focuses on reducing the extremely high levels of LDL-cholesterol. […] In 1998, the World Health Organization (WHO) officially recognized familial hypercholesterolemia as a global public health issue and published a set of 11 recommendations to address its burden. […] In January 2020, representatives from the global FH community published a Global Call to Action and highlighted a new set of recommendations, in 9 areas of priority, to reduce the clinical and public health burden of familial hypercholesterolemia.

• #51 Irish Heart Familial hypercholesterolemia (FH) – Irish Heart

  https://irishheart.ie/heart-and-stroke-conditions-a-z/famial-hypercholesterolaemia-fh/

  In people with FH, one of three genes involved in the removal of LDL-C from the blood may be altered. […] In people with FH, the faulty gene results in half of these receptors being either missing or not functioning normally. […] Without treatment, up to eight in every ten men with FH will have a heart attack. […] Women with FH also develop early heart disease but usually some years later than men. […] FH is passed from parent to child. […] If one parent has FH, half of their children are also likely to have FH. […] If you have FH, healthy eating alone will not lower your blood cholesterol enough, as your liver cannot remove excess cholesterol from your blood the same as someone who doesn’t have FH. […] For most people with FH, the aim of treatment is to lower the LDL-C level by at least half. […] Statins are the most commonly prescribed type of cholesterol lowering medicine. […] Lowering a high cholesterol level reduces the risk of stroke, heart attack, angina and the need for heart surgery.

• #52 What’s the difference between FH and standard high cholesterol? – BHF

  https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/familial-hypercholesterolaemia

  Too much fatty food is a cause of high cholesterol for many of us, but for about 250,000 people in the UK, its all in the genes. […] About one in 250 people has familial hypercholesterolaemia (FH), an inherited condition that means their cholesterol levels are higher than normal from birth. Its caused by an abnormal gene and, despite it putting people at high risk of early heart disease, most of them dont even know they have it. […] FH is caused by changes in one of three genes. Genes are the DNA instructions that our body uses to tell every cell how things should function. […] The genes involved in FH tell the body to produce proteins that are involved in clearing LDL cholesterol the harmful type of cholesterol from the bloodstream. So if one of them is faulty, then your body wont get the correct instructions.

• #53 The Tragic Truth About Familial Hypercholesterolemia

  https://www.acc.org/Latest-in-Cardiology/Articles/2015/09/24/17/25/The-Tragic-Truth-About-Familial-Hypercholesterolemia

  She came to me with severe muscle aches and very high cholesterol, hoping I could treat her, remembers Alan Brown, MD, FACC, a member of the Colleges Prevention of Cardiovascular Disease Section, and a specialist in preventative medicine. So I ran some tests, asked for a patient history and discovered she had Familial Hypercholesterolemia (FH), an inherited disease caused by a mutation in the low-density-lipoprotein (LDL) receptor gene. […] Had the prior doctors who saw this patient with markedly elevated LDL cholesterol (LCL-C) known to look for FH when LDL was 190 mg/dl, they may have been able to save Browns patient from heartache and save the life of her son. […] Although FH is the most common inherited metabolic disorder, occurring in one in 300 Americans, it is a largely undiagnosed condition. Many physicians in the medical community miss the FH diagnosis because they dont know to look for it.

• #54 The Tragic Truth About Familial Hypercholesterolemia

  https://www.acc.org/Latest-in-Cardiology/Articles/2015/09/24/17/25/The-Tragic-Truth-About-Familial-Hypercholesterolemia

  It is now recommended by ACC/American Heart Association guidelines that all children between nine and 11 years of age should have cholesterol testing. […] If one or more parents have high cholesterol or are known to have FH, their children should be tested at age two to five years old with FH treatment beginning by age seven. […] Both Brown and Gidding agree that FH should be treated early and aggressively. They recommend that when physicians see patients with elevated LDL-C, greater than 160 mg/dL in children and 190 mg/DL in adults, test for FH and test the whole family. […] This is a very treatable condition with the drug therapies and statins that are now available to us, notes Brown. The medical community holds the power to make the difference. Once they are aware of this incredibly common disorder, they can end the tragic stories, like my patients, by advocating for genetic testing and earlier treatment.

• #55 9 Things You Need to Know About Inherited High Cholesterol

  https://www.everydayhealth.com/high-cholesterol/treatment/10-things-you-need-to-know-about-inherited-high-cholesterol/

  If left undiagnosed and untreated, people with FH have a 20 times greater risk of developing heart disease, according to the American Heart Association. […] Patients are also susceptible to peripheral vascular disease and stroke much earlier than the general population. […] While a healthy lifestyle cannot fix familial hypercholesterolemia alone, it is still strongly encouraged. […] Statin medications are another layer of treatment for FH. […] A study in the July 2018 Frontiers in Pharmacology identified 14 treatment options for FH ranging from diet to fish oils to genetic therapy. […] Often, medical treatment is a last resort for children with any condition. But for FH, the earlier treatment happens, the better. […] A review published in the Journal of the American Heart Association found that universal lipid screening is recommended in children as early as age 2 for families with a history of high cholesterol and screenings around ages 9 to 11 for everyone else. […] Underberg says early diagnosis and treatment are akin to getting a car to a mechanic right away instead of waiting for it to break down.

• #56 Familial Hypercholesterolemia: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22067-familial-hypercholesterolemia

  Without treatment, people who have FH have 20 times the risk of coronary artery disease compared to someone without the disease. […] Since FH is a condition you inherit from your parents, it’s a part of your DNA all your life. You’ll need lifelong treatment. […] Healthcare providers don’t have a cure for familial hypercholesterolemia. But once you know you have FH, your provider can treat you for it and help you prevent cardiovascular disease. […] Getting treatment for familial hypercholesterolemia cuts down your risk of heart disease by more than half.

• #57 Familial Hypercholesterolemia | What We Do | World Heart Federation

  https://world-heart-federation.org/what-we-do/cholesterol/familial-hypercholesterolemia/

  FH is inherited. Typically, parents with one pathogenic mutation have a 50% chance of passing down the condition to each child. […] FH is severely underdiagnosed. Today, only 10% of individuals born with FH have been diagnosed worldwide. […] Early diagnosis and lifelong treatment of FH reduces the risk of premature cardiovascular disease and heart attacks. […] Individuals with FH can live longer and healthier lives if treatment begins early in life. […] In the case of FH, lifestyle and diet interventions are not enough. Patients will always require cholesterol-lowering therapies. […] FH drug treatment focuses on reducing the extremely high levels of LDL-cholesterol. […] In 1998, the World Health Organization (WHO) officially recognized familial hypercholesterolemia as a global public health issue and published a set of 11 recommendations to address its burden. […] In January 2020, representatives from the global FH community published a Global Call to Action and highlighted a new set of recommendations, in 9 areas of priority, to reduce the clinical and public health burden of familial hypercholesterolemia.

• #58 Mechanisms of disease: genetic causes of familial hypercholesterolemia – PubMed

  https://pubmed.ncbi.nlm.nih.gov/17380167/

  Familial hypercholesterolemia (FH) is characterized by raised serum LDL cholesterol levels, which result in excess deposition of cholesterol in tissues, leading to accelerated atherosclerosis and increased risk of premature coronary heart disease. FH results from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, commonly caused by a loss-of-function mutation in the LDL-receptor gene (LDLR) or by a mutation in the gene encoding apolipoprotein B (APOB). […] An autosomal recessive form of FH caused by loss-of-function mutations in LDLRAP1, which encodes a protein required for clathrin-mediated internalization of the LDL receptor by liver cells, has also been documented. The most recent addition to the database of genes in which defects cause FH is one encoding a member of the proprotein convertase family, PCSK9. Rare dominant gain-of-function mutations in PCSK9 cosegregate with hypercholesterolemia, and one mutation is associated with a particularly severe FH phenotype. […] Thus, PCSK9 is an attractive target for new drugs aimed at lowering serum LDL cholesterol, which should have additive lipid-lowering effects to the statins currently used.

• #59 Mechanisms of Disease: genetic causes of familial hypercholesterolemia · 研飞ivySCI

  https://www.ivysci.com/articles/1749052__Mechanisms_of_Disease_genetic_causes_of_familial_hypercholesterolemia

  Familial hypercholesterolemia (FH) is characterized by raised serum LDL cholesterol levels, which result in excess deposition of cholesterol in tissues, leading to accelerated atherosclerosis and increased risk of premature coronary heart disease. […] FH results from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, commonly caused by a loss-of-function mutation in the LDL-receptor gene (LDLR) or by a mutation in the gene encoding apolipoprotein B (APOB). […] An autosomal recessive form of FH caused by loss-of-function mutations in LDLRAP1, which encodes a protein required for clathrin-mediated internalization of the LDL receptor by liver cells, has also been documented. […] The most recent addition to the database of genes in which defects cause FH is one encoding a member of the proprotein convertase family, PCSK9.

• #60 About Familial Hypercholesterolemia

  https://www.genome.gov/Genetic-Disorders/Familial-Hypercholesterolemia

  More rarely, a person inherits the gene mutation from both parents, making them genetically homozygous. Individuals who are homozygous have a much more severe form of hypercholesterolemia, with heart attack and death often occurring before age 30. […] Familial hypercholesterolemia is inherited in an autosomal dominant manner. This means that to have this condition, it is sufficient that the altered (mutated) gene is present on only one of the person’s two number 19 chromosomes. A person who inherits one copy of the gene mutation causing familial hypercholesterolemia from one of his/her parents is said to have heterozygous familial hypercholesterolemia. […] A person who inherits a mutated copy of the gene causing familial hypercholesterolemia from both parents is said to have homozygous familial hypercholesterolemia. This is a much more severe form of familial hypercholesterolemia than heterozygous familial hypercholesterolemia.

• #61 Familial Hypercholesterolemia | Geisinger

  https://www.geisinger.edu/gchs/research/mycode/mycode-genomic-screening-and-counseling/familial-hypercholesterolemia

  If you have FH, your blood relatives should receive genetic testing. […] Your blood-related family members may have the same genetic change. In fact, your close blood relatives, including children, siblings and parents, have a 50 percent chance of having the same genetic change. […] In a few families, one person may have two FH-related gene changes — one inherited from each parent. This causes a more severe form of familial hypercholesterolemia, called homozygous familial hypercholesterolemia. […] If your blood relatives have FH, they should begin treatment to prevent heart issues. […] Your children should receive testing for their specific variant to learn if they inherited the risk for FH or not.

• #62 Familial Hypercholesterolemia | Geisinger

  https://www.geisinger.edu/gchs/research/mycode/mycode-genomic-screening-and-counseling/familial-hypercholesterolemia

  Familial hypercholesterolemia (FH) is an inherited condition that causes high cholesterol. […] Familial hypercholesterolemia (FH) is an inherited condition that causes high LDL cholesterol, or “bad cholesterol.” It’s often due to a change, or mutation, in one of your genes. […] Other factors can also cause FH. For instance, your doctor might make an FH diagnosis based on your LDL cholesterol level, physical exam findings and family history. […] When these genes are changed or aren’t working like they should, high levels of blood cholesterol can block your arteries and lead to dangerous conditions like heart disease, heart attack and stroke. […] All people with untreated FH have a higher risk of heart attacks and strokes as younger adults. People with FH who also have a change in their genes are at even higher risk.

• #63 Familial Hypercholesterolemia | What We Do | World Heart Federation

  https://world-heart-federation.org/what-we-do/cholesterol/familial-hypercholesterolemia/

  FH is inherited. Typically, parents with one pathogenic mutation have a 50% chance of passing down the condition to each child. […] FH is severely underdiagnosed. Today, only 10% of individuals born with FH have been diagnosed worldwide. […] Early diagnosis and lifelong treatment of FH reduces the risk of premature cardiovascular disease and heart attacks. […] Individuals with FH can live longer and healthier lives if treatment begins early in life. […] In the case of FH, lifestyle and diet interventions are not enough. Patients will always require cholesterol-lowering therapies. […] FH drug treatment focuses on reducing the extremely high levels of LDL-cholesterol. […] In 1998, the World Health Organization (WHO) officially recognized familial hypercholesterolemia as a global public health issue and published a set of 11 recommendations to address its burden. […] In January 2020, representatives from the global FH community published a Global Call to Action and highlighted a new set of recommendations, in 9 areas of priority, to reduce the clinical and public health burden of familial hypercholesterolemia.

• #64 Familial Hypercholesterolemia | What We Do | World Heart Federation

  https://world-heart-federation.org/what-we-do/cholesterol/familial-hypercholesterolemia/

  FH is inherited. Typically, parents with one pathogenic mutation have a 50% chance of passing down the condition to each child. […] FH is severely underdiagnosed. Today, only 10% of individuals born with FH have been diagnosed worldwide. […] Early diagnosis and lifelong treatment of FH reduces the risk of premature cardiovascular disease and heart attacks. […] Individuals with FH can live longer and healthier lives if treatment begins early in life. […] In the case of FH, lifestyle and diet interventions are not enough. Patients will always require cholesterol-lowering therapies. […] FH drug treatment focuses on reducing the extremely high levels of LDL-cholesterol. […] In 1998, the World Health Organization (WHO) officially recognized familial hypercholesterolemia as a global public health issue and published a set of 11 recommendations to address its burden. […] In January 2020, representatives from the global FH community published a Global Call to Action and highlighted a new set of recommendations, in 9 areas of priority, to reduce the clinical and public health burden of familial hypercholesterolemia.

• #65 The Tragic Truth About Familial Hypercholesterolemia

  https://www.acc.org/Latest-in-Cardiology/Articles/2015/09/24/17/25/The-Tragic-Truth-About-Familial-Hypercholesterolemia

  FH is incredibly common and can dramatically shorten life expectancy but it is also incredibly silent due the fact that severely high cholesterol causes no symptoms. […] FH, which causes high levels of LDL-C, presents with no differentiating symptoms from high cholesterol and can only be diagnosed by a screening lipid profile. […] Although the management of FH is the same as other causes of high cholesterol by missing the diagnosis of FH and starting treatment too late in life, family members of the patient remain vulnerable to cardiac events. […] Lack of symptoms, compounded with lack of awareness, leaves the condition largely undiagnosed until a precipitating event such as a heart attack occurs, adds Gidding. […] In almost all cases, earlier testing and treatment of FH patients would have led to better outcomes.

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