Homozygous and heterozygous
Homozygous familial hypercholesterolemia
The treatment of patients with homozygous familial hypercholesterolemia is very challenging, as their liver surfaces lack specific low-density lipoprotein (LDL) receptors. Dietary treatment and most cholesterol-lowering drugs are ineffective for these patients, and even gastric bypass surgery has no effect. However, due to the cholesterol-lowering effect of propofol(developed by a British pharmaceutical company called Imperial Chemical Industries) not relying on the LDL receptor pathway, it can moderately reduce blood cholesterol levels and shrink some patients’ xanthomas. Additionally, plasma exchange therapy can selectively clear very low-density lipoprotein-cholesterol (VLDL-C) and low-density lipoprotein-cholesterol (LDL-C) from the blood, making it suitable for the treatment of this type of patient. This treatment helps to slow down the formation and development of atherosclerosis.
Heterozygous familial hypercholesterolemia
The treatment of heterozygous familial hypercholesterolemia patients includes two aspects: dietary treatment and medication. These patients can simply use cholestyramine, nicotinic acid, or statin drugs to lower serum total cholesterol levels. For severe patients, combined medication such as cholestyramine and nicotinic acid or cholestyramine and statin drugs is recommended. Some studies have shown that on the basis of dietary treatment, long-term combined use of two or three lipid-lowering drugs can inhibit the development of atherosclerosis or partially regress atherosclerotic plaques. If patients cannot tolerate drug treatment, gastric bypass surgery can help lower serum cholesterol levels.
Homozygous familial hypercholesterolemia (HoFH) and heterozygous familial hypercholesterolemia (HeFH) are two distinct forms of a genetic disorder characterized by extremely high levels of low-density lipoprotein (LDL) cholesterol, often referred to as “bad” cholesterol. This condition significantly increases the risk of premature cardiovascular disease, including heart attacks and strokes. The primary difference between HoFH and HeFH lies in the number of faulty genes an individual inherits and the severity of the condition.
Homozygous Familial Hypercholesterolemia (HoFH):
- Genetic Inheritance: Individuals with HoFH inherit two defective copies of the gene responsible for encoding the LDL receptor, one from each parent. This means they are homozygous for the mutation, hence the term “homozygous.”
- Severity: HoFH is a much rarer and more severe form of familial hypercholesterolemia. The lack of functional LDL receptors prevents the body from clearing LDL cholesterol effectively, leading to extremely high levels of cholesterol from a very early age.
- Clinical Manifestations: People with HoFH often develop severe atherosclerosis (hardening of the arteries) in childhood, and they may exhibit noticeable skin and tendon xanthomas (deposits of cholesterol) and premature corneal arcus (a white or gray ring around the cornea).
- Treatment Challenges: Management of HoFH is challenging and typically requires aggressive treatment strategies, including lipid-lowering medications, regular cholesterol apheresis (a procedure to remove LDL cholesterol from the blood), and sometimes even surgical interventions like liver transplantation.
Heterozygous Familial Hypercholesterolemia (HeFH):
- Genetic Inheritance: Individuals with HeFH inherit one defective copy of the LDL receptor gene and one normal copy. This heterozygous state means they have a mix of functional and non-functional genes.
- Severity: HeFH is more common and generally less severe than HoFH. While these individuals also have elevated LDL cholesterol levels, the severity and onset of cardiovascular issues are typically later in life compared to HoFH.
- Clinical Manifestations: People with HeFH may develop xanthomas and corneal arcus, but these are generally less prominent than in HoFH. Cardiovascular disease often becomes a concern in adulthood.
- Treatment: Treatment for HeFH usually involves lifestyle modifications (diet, exercise) and medication to lower cholesterol levels. Statins are commonly prescribed, and in some cases, additional medications or cholesterol apheresis may be necessary.
In summary, the key differences between HoFH and HeFH are the number of defective LDL receptor genes inherited (two for HoFH, one for HeFH), the severity of the condition (more severe in HoFH), the age of onset for cardiovascular problems (earlier in HoFH), and the complexity of treatment required (more aggressive in HoFH). Both conditions underscore the importance of genetic testing and early intervention in managing inherited cholesterol disorders.
