Familial Hypercholesterolemia: A Literature Review of the Pathophysiology and Current and Novel Treatments

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.