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Published on: September 15, 2018
Familial Hypercholesterolemia: A Literature Review of the Pathophysiology and Current and Novel Treatments
Yasha N Suryawanshi1, Rupesh A Warbhe2
1Department of Physiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND.
Insights
Familial hypercholesterolemia (FH) is an inherited metabolic disorder causing high LDL cholesterol due to genetic mutations. Early diagnosis and effective treatments are crucial to prevent premature cardiovascular disease.
Area of Science:
- Genetics
- Metabolic Disorders
- Cardiovascular Disease
Background:
- Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder.
- It is characterized by elevated low-density lipoprotein (LDL) cholesterol levels.
- Mutations in genes like LDLR, apoB, PCSK9, and LDLRAP1 are primary causes.
Purpose of the Study:
- To summarize the genetic basis of Familial hypercholesterolemia.
- To highlight the link between FH and early-onset cardiovascular disease.
- To emphasize the importance of early diagnosis and treatment.
Main Methods:
- Review of genetic mutations associated with FH.
- Analysis of the role of LDL receptor (LDLR) in cholesterol metabolism.
- Description of FH inheritance patterns (heterozygous vs. homozygous).
Main Results:
- FH leads to impaired LDL clearance, causing atherosclerosis at a young age.
- Homozygous FH (HoFH) presents more severe cardiac issues than heterozygous FH (HeFH).
- Genetic defects in LDLR are the most common cause of FH.
Conclusions:
- Early diagnosis and effective management of FH are essential to prevent cardiovascular events.
- Novel therapies are emerging to manage elevated LDL cholesterol levels.
- Understanding FH genetics is key to developing targeted treatments.
Abstract:
Familial hypercholesterolemia (FH) is a genetically transmitted disorder. It shows an autosomal dominant mode of inheritance. It is a metabolic disorder. Mutation in chromosome 19 leads to this disorder. Chromosome 19 codes data for low-density lipoprotein (LDL) receptor (LDLR). LDLR either reduces increased LDL levels from the circulation or maintains a normal level of LDL. It precipitates the risk of cardiovascular disease at an early age. Characteristic features of FH are elevated levels of LDL in the blood because of sudden changes in LDLR, which causes a decrease in the clearance of LDL from the blood. Plaque gets deposited in the lumen of the arteries, called atherosclerosis, which occurs at an early young age. If both genes are affected then it is homozygous FH (HoFH); such a case is very rare. When a single gene is affected then that condition is known as heterozygous FH (HeFH). HoFH comes up with more severe cardiac disease than HeFH at an early age. The major cause of FH is a mutation in the LDLR gene while other causes include mutation in various genes like apolipoprotein B (apo B), proprotein convertase subtilisin/kexin type 9 (PCSK9), LDLR adaptor protein 1 (LDLRAP 1). In order to prevent cardiovascular crises due to FH, it must be diagnosed early and treated effectively. With increasing research and advances in medical sciences, many kinds of current and novel therapies are emerging that aim to reduce the level of LDL in blood.
