Review explores genetic variants and contributing factors in familial hypercholesterolemia

Familial Hypercholesterolemia (FH) is a genetically transmitted metabolic disorder characterized by elevated levels of low-density lipoprotein (LDL) in the blood, leading to a heightened risk of cardiovascular disease at an early age. The disorder results from a mutation in the gene encoding the low-density lipoprotein receptor (LDLR) on chromosome 19, affecting the clearance of LDL from the bloodstream.

A recent review explored the pathophysiology of this disease as well as current and novel treatments.

Key Points:

1. Genetic Basis: FH is an autosomal dominant disorder transmitted through a mutation in chromosome 19, affecting the LDLR gene responsible for regulating LDL levels in the blood.
2. Cardiovascular Risk: Individuals with FH face an increased risk of cardiovascular disease due to elevated LDL levels, leading to the premature deposition of plaque in the arteries (atherosclerosis) and potential cardiac crises at an early age.
3. Forms of FH: FH presents in two forms – homozygous FH (HoFH) and heterozygous FH (HeFH). HoFH, resulting from the mutation of both LDLR gene copies, is rare and more severe, causing advanced cardiac disease in early life. HeFH, with a single affected gene, is more common.
4. Contributing Genes: While the primary cause of FH is a mutation in the LDLR gene, other contributing factors include mutations in genes such as apolipoprotein B (apo B), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDLR adaptor protein 1 (LDLRAP 1).
5. Therapeutic Advances: Timely diagnosis and effective treatment are crucial to prevent cardiovascular crises associated with FH. Ongoing research and advances in medical sciences are yielding various current and novel therapies aimed at reducing LDL levels in the blood, offering hope for improved outcomes and cardiac health for individuals with FH.

Reference
Suryawanshi YN, Warbhe RA. Familial Hypercholesterolemia: A Literature Review of the Pathophysiology and Current and Novel Treatments. Cureus. 2023 Nov 20;15(11):e49121. doi: 10.7759/cureus.49121. PMID: 38125244; PMCID: PMC10732334.