is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL, "bad cholesterol"),

in the blood and early cardiovascular disease.

 mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation,

mutation
apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor

 Heterozygous premature cardiovascular disease at the age of 30 to 40 1:500 people in most countries

Homozygous cause severe cardiovascular disease in childhood 1 in a million births

 Class I: LDLR is not synthesized at all. Class II: LDLR is not properly transported from the

endoplasmic reticulum to the Golgi apparatus for expression on the cell surface. because of a defect in either apolipoprotein B100 (R3500Q) or in LDL-R.

Class III: LDLR does not properly bind LDL on the cell surface Class IV: LDLR bound to LDL does not properly cluster in
clathrin-coated pits for receptor-mediated endocytosis.

Class V: LDLR is not recycled back to the cell surface.

addition to being the essential structural component of VLDL, apoB-100 is the ligand for LDL-receptor-mediated endocytosis of LDL particles. Many nonsense, frameshift, and splicing mutations in the APOB gene leading to formation of prematurely truncated apoB forms These mutations in apoB cause the production isoforms of various lengths because of the missing carboxyl-terminal portion of the molecule. These truncations are named according to a centile system and range from apoB-6.46 to apoB-89 Mutation can reduce the affinity to the LDL receptor by at least 95%

Heterozygous FH usually treated with statins HMG-CoA-reductase inhibitors bile acid sequestrants (cholestyramine or colestipol) nicotinic acid fibrates

Homozygous FH
Only high doses of statins, often in combination with other medications, are modestly effective Dialysis liver transplant; this provides a liver with normally functional LDL receptors Inhibition of the microsomal triglyceride transfer protein (in future) infusion of recombinant human apolipoprotein A1 (in future)