17 - Familial Hypercholesterolaemia Flashcards
Cholesterol
- Needed to form cell membranes and hormones
- Can be obtained from food or synthesised in the liver
- Some saturated fats are cholesterol free but cause an increase in cholesterol
- Aren’t water soluble (transport via lipoproteins)
Exogenous lipoprotein metabolism pathway
Gut makes lipoproteins to bring dietary fats to the liver
Endogenous lipoprotein metabolism pathway
Liver makes lipoproteins to take cholesterol to peripheral tissues
Reverse cholesterol transport lipoprotein metabolism pathway
HDL brings cholesterol back from peripheral tissues to liver
Primary causes of hypercholesterolaemia
- Familial hypercholesterolaemia
- Polygenic hypercholesterolaemia
Secondary causes of hypercholesterolaemia
- Diet rich in saturated fats
- Hypothyroidism
- Nephrotic syndrome
- Liver disease
Familial hypercholesterolaemia
- Autosomal dominant
- Defect in the LDL receptor pathway leads to raised total and LDL cholesterol
- Clinical manifestations include corneal arcus, xanthelasma, coronary artery disease
Gene mutations that cause FH
LDLR, APOB, or PCSK9
ApoB
Act as ligand, binding LDL particle to receptor
LDL receptor
On hepatocyte, binds to apoB on LDL particle, inducing endocytosis of LDL
PCSK9
Degrades LDL receptors
How is FH detected
- Sequencing (NGS)
- MLPA (deletion/duplication analysis)
Polygenic hypercholesterolaemia
Having a greater than average number of common, cholesterol-raising genetic variants that, together, have a large effect on the plasma concentration of LDL-cholesterol
Treatment of FH
- Aimed at lowering plasma LDL cholesterol
- Correction of risk factors (diet, smoking)
- Statins
- PCSK9 inhibitors
- Severe FH –> LDL apheresis
Homozygous FH
- Very rare
- Coronary atherosclerosis in childhood
- Hard to treat
