Primary defect is a deficit of low-density lipoprotein receptors, a monogenic disorder.
familial hypercholesterolemia is present in one in 250 to 350 children and is the most common primary lipid disorder of childhood.
One in 250 people are heterozygous for genetic mutation, and 1 in a million is homozygous for the low-density lipoprotein receptor gene.
An autosomal dominant disorder characterized by elevations in low-density lipoprotein cholesterol (LDL-C).
In a matter-analysis involving 11 million adults, the worldwide prevalence of familial hypercholesterolemia among those in severe hypercholesterolemia was 7.2%.
Associated with genetic variants that result in virtually absent or impaired LDL-receptor activity.
A relatively common Mendelian genetic disorder associated with markedly elevated low density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease.
Patients with heterozygous familial hypercholesterolemia, have plasma cholesterol levels 2-3 times the levels in individuals without disease, but because they have one functional copy of the LDL receptor, they still have some degree of response to standard cholesterol lowering medications.
Associated with severely elevated plasma levels of LDL cholesterol from birth onward and these patients are at very high risk of premature cardiovascular disease.
Coronary heart disease in FH potentiated by risk factors such as smoking, hypertension, obesity, and diabetes.
There is an association of raised lipoprotein(a) plasma concentrations with coronary heart disease in patients with FH.
Lipoprotein(a) is an LDL-like particle with additional apolipoprotein, apolipoprotein(a), attached to apolipoprotein B.
Caused by a loss of function mutations in both alleles of low density lipoprotein receptor gene.
Caused by transmission of defects on the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB), or the proprotein convertase subtilisn/kexin type 9 gene (PCSK9) all of which cause reduced LDL plasma clearance.
Pathogenic variants in one of three genes-LDLR, APOB, or PCSK9 account for most cases.
Familial hypercholesterolemia Is caused by variants in genes encoding proteins involved in the clearance of LDL particles.
Pathologic variants in LDLR lead to impaired LDL receptor function in elevated LDL-C levels.
Impaired hepatic cholesterol uptake characterized by high plasma levels of low-density lipoprotein cholesterol.
Increased risk for premature cardiovascular disease.
Unteated FH associated with a significantly shortened life expectancy, with sudden death and myocardial infarction as the principal causes of death.
Homozygous persons have severe coronary atherosclerosis and usually die in childhood from myocardial infarction.
Increased rate of progression of intimal-media thickness in childhood.
Patients have plasma cholesterol levels of more than 500 mg per deciliter and patients do not generally survive past 30 years of age.
Patients have poor response to conventional drugs which lower LDL cholesterol via up-regulation of hepatic LDL receptor.
Patients may be at lower risk to develop type 2 diabetes.
Statins are the preferred drug therapy in treatment should start at a young age.
The optimum age of initiation of statins is from as young as 8-10 years of age.
The initiation of statin therapy during childhood in patients with familial hypercholesterolemia slow the progression of carotid into a-media thickness and reduced the risk of cardiovascular disease in adults (Luirink LK).
Present care consists of LDL apheresis which can transiently reduce LDL cholesterol levels by more than 50% and may delay the onset of vascular disease.
Lipid-lowering treatment improves life expectancy.
Most patients do not achieve LDL-C levels less than 100 mg/dL.
Apheresis must be repeated every 1-2 weeks.