Introduction
Most people know that fatty foods increase cholesterol levels in the body. However, some people inherit cholesterol from their parents. Genetically acquired illnesses are sometimes quite dangerous. One such inherited illness is familial hypercholesterolemia (FH). FH can be defined as an inherited condition in which the level of bad cholesterol is elevated than that of normal cholesterol. Bad cholesterol is usually known as low-density liloprotein (LDL). In most cases, fatty lumps around the eye characterise the disease (1). However, fatty lumps can also appear anywhere on the skin. Having a routine check up can help in discovering the condition. Studies show that one in every 500 people is thought to have FH (8). Treatment for FH usually includes medication and a healthy living aimed at containing the level of cholesterol. This paper will explore the pathogenesis, genetics, clinical symptoms, prognosis and dietary management of familial hypercholesterolemia (1).
Pathogenesis and genetics
FH is known as a disorder associated with grossly malfunctioning or missing LDL receptors. Usually, this receptor is situated in the diminutive arm of chromosome 19. It should be noted that protein around this layer contains 860 amino acids (3). These receptors determine hepatic LDL uptake and therefore process about 70 per cent of LDL that circulates. ApoE and apolipoprotein B-100 are bound to the LDL receptor. This is why the receptor is sometimes known as the BE receptor. ApoE is found in all loliproteins except LDL. It should also be noted that apoE binds more with the LDL receptor than apoB (4).
According to research studies done by Goldstein and Brown in the years 1973 and 1974 respectively, FH defects is mainly in the cell membrane receptor for the low-density liloprotein cholesterol. Usually, the LDL cholesterol is moved to the cell ending by lysosomes (4). At this point, protein is usually degraded upon which cholesterol is repressed for “microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase,” which is sometimes shortened as (HMGCoA). This process acts to limit rate in synthesis of cholesterol. However, in FH, a dysfunctional receptor causes binding effect. Moreover, synthesis of cholesterol ester also occurs. Further studies showed that liver membrane also acts as a site for receptor defect. Harders-Spendel et al. conducted this research, in 1982. Additional research in 2001 showed that high levels of LDL cholesterol were closely linked to low weight of children at birth. Moreover, not only were LDL cholesterols present but apolipoprotein B cholesterols were also present (4).
More research by Ijzerman et al., showed interesting outcomes. The research was aimed at examining the influences of genetic as well as intrauterine factors on atherogenic lipids as life continues. To achieve this, the researchers considered 61 monozygotic and 53 dizygotic adolescent. These were in pairs. The cholesterols were found to persist in dizygotic adolescent. However, these cholesterols were found to reverse in monozygotic pairs. Additionally, the researchers observed that the relationship between low levels of HDL cholesterol and low weight at birth persisted in both cases. This could be seen during the intrapair analysis of the twins. In essence, data observed showed that genetic factors could explain the occurrence of high level of cholesterol with low weight at birth. Furthermore, genetic factors could also explain the association of low levels of HDL cholesterol with low weight at birth. Concisely, these researchers proved that genetic factors also account for development of FH (7).
According to Garcia-Otin et al., further studies found that intestinal cholesterol absorption was very high in ADH without recognised defect. This was followed by ADH with recognised defect. The third was controls and finally FCHL (familial combined hyperlipidemia). This experiment was done on well-phenotyped patients who suffered from dyslipidemias as well as ADH (autosomal dominant hypercholesterolemia). Additionally, it should be noted that the patients had known and unknown genetic defects including FCHL at the time of research (7). These researchers concluded that lipid abnormalities could have been caused by intestinal cholesterol absorption in patients with ADH without known genetic defects. Based on the resulting evidence, these researchers suggested that serum noncholesterol sterols be considered as a valuable tool for diagnosis of FH (9).
Clinical symptoms
Children who suffer from homozygous FH usually have symptoms, which are similar to those with aortic stenosis. These may include arthralgias and tendosis. Such patients also experience unique skin lesions. These patients can exhibit symptoms related to CHD. Corneal arcus can sometimes be observed in such patients. Moreover, aortic stenosis murmur can also be observed. On the other hand, children with heterozygous FH do not exhibit symptoms associated with CHD. It should also be noted that most children with heterozygous FH rarely develop xanthomas neither do they acquire corneal arcus (10).
Adults with homozygous FH rarely live more than 30 years if not treated with complex medications like LDL apheresis, liver transplant or ileal bypass surgery. On the other hand, adults with heterozygous FH usually have a history of severe FH from infancy. Symptoms associated with ischemic heart illness are usually common especially if the patients smoke. However, this happens if the patient has no previous history of acute coronary event. Arthritis and Achilles tendonitis may also recur in such patients. Furthermore, if patients are not attended to, over 60 per cent develop tendon xanthomas within 30 years of their lives. Another symptom in adults with heterozygous FH is xanthelasmas (2).
Diagnosis
Diagnosis of FH is usually based on examining severe increase in LDL as well as the absence of other possible causes of the disease. The same idea is utilised in diagnosis of both heterozygous and homozygous FH. In most cases, heterozygous FH is diagnosed whenever the LDL increase beyond 330mg/dL. The same diagnosis can also be made whenever the LDL increase beyond the 95th per centile. This is usually accompanied by tendon xanthomas (9). Note that the methods named above are for probable diagnosis. When definitive diagnosis is required, then receptor or gene analysis is required. Nonetheless, high levels of serum triglyceride also increase the probability of having lipid disorder. Whenever testing is done on lipids of patients with FH, a number of observations are usually made (5). Homozygous FH is diagnosed if LDL level is beyond 600mg/dL with normal levels of triglyceride. On the other hand, heterozygous FH is diagnosed if LDL level is higher than 250mg/dL. However, it can also be diagnosed if the LDL levels are beyond 200mg/dL for patients below 20years of age. Nonetheless, LDL levels of between 290 and 3000mg/dL may also imply heterozygous FH (8).
Analysis on LDL receptors is essential in identifying LDL receptor defect. Additionally, it can be used to isolate heterozygous FH. Screening for FH is recommended for patients whose family member has been diagnosed with FH. Moreover, it is to be done to adult patients with 310mg/dL or more cholesterol. Furthermore, screening is proposed for children with 230mg/dL or more. Screening can also be done for patients with tendon xanthomas, premature CHD and cardiac death (3).
Prognosis
Cholesterol is deadly if its level is not monitored closely. No wonder, it is sometimes referred to as silent killer. Patients with FH risk suffering from heart attack early in their life if they are not diagnosed and they are not treated in time. In most cases, patients with FH have a history of heart disease and elevated level of cholesterol in the family. This disease has no cure but it can be managed if detected early and treated. When a child inherits FH from both parents, his/her situation is usually more severe than one who acquires from one parent (6).
Dietary management
The best mode of treating FH is to maintain a healthy lifestyle and diet. Additionally, statins can also be used in treatment of FH. When these treatment methods are applied successfully, the risk of developing coronary heart disease is greatly lowered. Moreover, the chances of getting heart attack are lowered. Patients should change their diet in this manner (10). They should eat less lamb, chicken, beef and pork. Additionally, they should replace full fat dairy products with low fat ones. They should also avoid organ meats, palm oils, egg yolks and coconut. Regular exercise, weight loss and counselling are also important for patients. If the changes above do not work then, other medicines for lowering cholesterol include Nicotinic acid, Ezetimibe, bile acid and fibrates, among others (11).
Conclusions and recommendations
FH is a condition, which is passed through genes. The passage of the disease happens in autosomal dominant mode. FH is manly characterised by high levels of LDL cholesterol, also known as the bad cholesterol. Children diagnosed with FH are at risk of heart attack even at a younger age. This is possible especially if the child acquires FH from both parents. If left untreated, FH can lead to heart attack. People with affected relatives should seek screening for diagnosis of FH. Moreover, patients with FH should live healthy lifestyles and should feed on a healthy diet, which cuts on cholesterol. Additionally, such patients should avoid smoking as this increases risk of FH.
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