Familiar Hypercholesterolemia Pathophysiology

It is doubtless that there are countless diseases and disorders, which affect the normal functioning of the human body. Although some of these ailments are manageable, it is essential to note that some can be fatal and costly to control or treat. This analysis discusses familial hypercholesterolemia, a disorder that has been found to be rare, in most countries around the world, with a prevalence of one out of every one million births. In particular, the paper will cover the disease’s pathophysiology mechanism, exploring its molecular pathophysiology, genetic and cancer biology, immunology and clinical manifestations.

What is familial hypercholesterolemia?

Familial hypercholesterolemia, abbreviated as FH, is described as a genetic disorder, which results in high levels of low-density lipoprotein, LDL. This is commonly observed during the early stages after a child’s birth, and victims are usually exposed to high levels of a heart attack. Notably, cholesterol occurs naturally in body cells and can also be obtained from certain foodstuffs.

It is an essential element required by the body, for the production of hormones, certain vitamins and other components, which are paramount during digestion. Whilst cholesterol is vital for the normal functioning of the body, it is worth noting that its excessive build-up is risky; may block some arteries, thus exposing the victim to heart diseases (McCance & Huether, 2009).

Additionally, the transportation of cholesterol in the body is aided by the presence of lipoproteins, which are made of fats and proteins. Lipoproteins naturally occur in two types, namely, low and high-density lipoproteins, abbreviated as LDL and HDL, respectively (Zetterstro¨m, 2011).

Due to its effects, cholesterol, which is transported by LDL, is commonly known as “bad cholesterol.” As indicated above, patients with familial hypercholesterolemia register high levels of LDL cholesterol, since their bodies do not have efficient mechanisms to reduce its concentration. The liver is responsible for the regulation and removal of LDL (McCance & Huether, 2009). However, its malfunctioning may lead to this condition and cause victims to become more vulnerable to dangerous conditions like a heart attack.

On the other hand, cholesterol that is transported by HDL is considered to be good cholesterol. This is because HDL ferries cholesterol to the liver, which eliminates it from the body through biological mechanisms. In essence, people with a low concentration of cholesterol have lower chances of developing heart attacks and other related infections.

Familial hypercholesterolemia affects men and women, even though there is a slight variation in the time when heart attack affects victims. Most men with FH suffer from heart attacks in their 40’s and 50’s (McCance & Huether, 2009). In contrast, women who have familial hypercholesterolemia experience heart attacks ten years later than in their male counterparts.

Another important factor to note about familial hypercholesterolemia is that it is a genetic infection, as it is inherited through autosomal dominance. This implies that parents with FH-causing gene, which is usually altered, have a fifty percent chance of passing the same gene to their children. The altered gene, which is usually responsible for such infections, occurs in chromosome number nineteen. Additionally, the gene is coded with information for LDL receptors, which has the potential of eliminating LDL from the blood stream (McCance & Huether, 2009).

People who have altered genes, which cause familial hypercholesterolemia, are generally referred to as heterozygotes. In very rare cases, a person may inherit altered genes from both parents. In such scenarios, victims are usually considered to be genetically homozygous. Homozygous patients experience severe side effects of familial hypercholesterolemia, coupled with chronic heart attacks. As a result, death may occur before one is thirty years old (Jones, Lakasing & Archontakis, 2009).


In the understanding of familial hypercholesterolemia, it is essential to note that it has a wide range of clinical manifestations. As a result, it is not easy to tell that one is suffering from FH before a thorough medical check-up is carried out (Jones, Lakasing & Archontakis, 2009). However, the following signs and symptoms have been observed among patients suffering from the disease. Firstly, this disorder is characterized by high levels of LDL cholesterol and total cholesterol, accompanied by early cases of heart attack.

Additionally, it is possible to tell that a child has FH if his or her parents exhibit high levels of LDL therapy-resistance. In other cases, patients may have deposits of cholesterol in their skins, appearing to be waxy (McCance & Huether, 2009). Besides the skin, cholesterol deposits may be observed in eyelids and cornea of suspected individuals. Lastly, familial hypercholesterolemia is known to cause chest pain.

Pathophysiology of FH

As mentioned above, the occurrence of heterozygous phenotypes is mainly attributed to alteration of genes, which is scientifically referred to as gene mutation. In most cases, these mutations affect NARC, apoB100 and LDL receptors, which are generally characterized by an increase in “bad cholesterol.” Importantly, FH affects the normal functioning of the body and may lead to an array of physiological disturbances, which may not necessarily be described as a disease (Gunder & Martin, 2011).

LDL Receptor Defects

Higher concentration of cholesterol affects the cells within the surrounding. Oftentimes, FH has been found to occur as a result of inappropriate metabolism of lipoprotein, which principally minimizes the activities or the potential for LDL receptors to be expressed (Puntoni et al., 2011). As a result, the removal of hepatic LDL from the body is hampered. Most researchers have agreed that this level of reduction usually predisposes one to the development of atherosclerosis.

This is commonly observed when one develops familial hypercholesterolemia or as a result of ingesting high levels of cholesterol (Gunder & Martin, 2011). Furthermore, individuals who experience elevated secretion of VLDL can get exposed to a mixture of dyslipidaemia or hypercholesterolemia. These conditions are highly exhibited, with other complications like diabetes 2 and extreme obesity equally occurring.

In addition, hepatocyte has a high supply of cholesterol. Even though the manufacture and secretion of cholesterol can be monitored and regulated, elevated levels of LDL cholesterol in plasma can trigger an increase in uptake and storage of these fat-like substances. It has been postulated that this uptake and storage of cholesterol lead to the production of lipoprotein, which is broadly associated with familial hypercholesterolemia (Rose, 2010).

Patients, who experience malfunctioning LDL and receptors genes, are likely to suffer severely since the elimination of LDL could be too low to be felt or absent. It is therefore important to note that the synthesis of cholesterol may differ among people depending on a number of factors, including but not limited to dietary, absorption of cholesterol and the release or uptake of bile acids. These variations equally affect a person’s ability to cope with familial hypercholesterolemia (Puntoni et al., 2011).

Moreover, LDL receptor defects are classified in several groups. This classification is manly based on a wide range of factors, including but not limited to the maturity of cells, the impact of gene alteration, existing differences between immunoglobulin and LDL, and the degradation of LDL receptors. In the first class, mutations are mainly caused by promoter mutations. Additionally, it is not possible to detect mRNA and LDL receptors (Rose, 2010).

On the other hand, defects in the second category are as a result of mutations, which mainly affect proper development and maturation of LDL receptors. Similarly, defects in the third class are observed due to the inability of receptors to bind ligands properly. The fourth group consists of defects, which occur due to mutations that take place in the cytoplasmic tail of LDL receptors. Furthermore, group 5 defects are highly associated with degradation of receptor cells while the last class of defects is as a result of poor direction given to LDL receptors (Zetterstro¨m, 2011).

Besides LDL receptor complications, familial hypercholesterolemia is also associated with familial binding defective apoB100, commonly abbreviated as FDB (Friedrich, 2010). However, research has indicated that FDB is less severe in children as compared to LDL defects. This observation has been attributed to high levels of LDL receptor activities, as one advances in age.

In other cases of comparison, it was found out that LDL receptors led to an increase in the concentration of plasma lipoprotein and was linked to numerous coronary artery problems. Importantly, oxidized LDL contributes to the development of atherosclerosis in several ways. These include destruction of the endothelium, growth inhibition and use of macrophages. Furthermore, the presence of oxidized LDL leads to a low production of vasodilator nitric oxide in cases where the endothelial wall has been tempered with (Friedrich, 2010).


Friedrich, D. (2010). Heterozygous familial hypercholesterolemia case study. Journal of the American Academy of Nurse Practitioners, 22, 523–526.

Gunder, L., & Martin, S. (2011). Essentials of Medical Genetics for Health Professionals. Massachusetts: Jones & Bartlett Learning.

Jones, J., Lakasing, E., & Archontakis, S. (2009). Familial hypercholesterolemia: different perspectives. Nursing Standard, 23 (50), 35-38.

McCance, K., & Huether, S. (2009). Pathophysiology: The Biologic Basis for Disease in Adults and Children. Amsterdam: Elsevier Health Sciences.

Puntoni et al. (2011). Myeloperoxidase modulation by LDL apheresis in Familial Hypercholesterolemia. Lipids in Health and Disease, 10 (185), 1-8.

Rose, K. (2010). Guide to Paediatric Drug Development and Clinical Research. Connecticut: Karger Publishers.

Zetterstro¨m, R. (2011). Investigations on a child with familial hypercholesterolemia. Acta Pædiatrica, 100, 311–313.

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