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Familial Hypercholesterolemia - Coggle Diagram
Familial Hypercholesterolemia
Genetic Details
Most common autosomal dominant disorder and is the result of any of thousands of types of mutations that can affect LDL receptors
heterozygous occurs 1:500, homozygous occurs 1:1,000,000
heterozygous are not affected as severely as homozygous
Pathophysiology
Thousand of mutations can occur to affect the LDL receptor and its ability to carry LDL back into the cell
Circulating LDL is needed inside the cell for cell function in the plasma membrane. Cholesterol levels are controlled by LDL receptors that bind to LDL in the bloodstream and carry back into the cell. When mutations lead to dysfunctional LDL receptors, circulating cholesterol levels grow too high. This leads to fatty plaques in small vessels causing myocardial infarction or stroke.
treatments are aimed at reducing reabsorption and
synthesis of cholesterol in the body to reduce circulating LDL
Medications are being tested that aim to inhibit the PCSK9 enzyme. PCSK9 is an enzyme that destroys LDL receptors. By stopping PCSK9, homozygous FH patients can maintain more LDL receptors and circulating LDL levels can be drastically reduced. By combining with a statin drug that works to inhibit cholesterol synthesis by the liver, circulating cholesterol levels can be reduced even more
Risk Factors
family history of first degree relative with FH
Men are higher risk than women; studies show men with LDL greater than 190 mg/dL and younger in age should be evaluated for FH and early intervention
Diagnostic Testing
Total cholesterol:
homozygous: 300-400 mg/dL
heterozygous: 600-1200 mg/dL
young adults with LDL > 190mg/dL, especially with family history of CAD and MI
Presenting Signs & Symptoms
(that lead to suspicion of FH)
known family history of FH or coronary artery disease/MI in a first degree relative younger than 55
myocardial infarction, stroke or atherosclerosis in pt under 60 years old
Total cholesterol greater than 400mg/dL
xanthoma (fatty deposits) in skin and tendons, often seen in knuckles
Treatments
heterozygotes can reach normal cholesterol levels when combining a cholestyramine with a statin medication to reduce reabsorption of cholesterol in the gut and decreasing cholesterol synthesis in the liver
heterzygotes can also benefit slightly from decreasing cholesterol in their diet
New studies are aimed at exploring medications that inhibit PCSK9. Studies show success in these medications combined with statin
treatment options for homozygous FH patients currently is limited to plasma exchange to reduce circulating LDL, gene therapy to inject functional LDL receptor genes into the liver, and liver transplant when possible