Familial Hypercholesterolemia (FH)
by Arianny Perrino Lanz
1. Phatophysiologic Ethiology
1.1. Is an important cause of heart disease, causing 5% of myocardial infarctions (McCance & Huether, 2015).
1.2. Autosomal dominant disorder characterized by a high plasma level of low-density lipoprotein cholesterol (LDL) (Kullo, n.d.).
2. Genetic Details
2.1. This example shows the molecular basis of familial hypercholesterolemia with dominant pattern of inheritance: impaired low-density lipoprotein cholesterol clearance due to variations in LDLR, APOB, PCSK9 (Kullo, n.d.).
2.1.1. FH is caused by a mutation in one of three genes the low-density lipoprotein cholesterol receptor (LDLR), apolipoprotein B gene (APOB), or a gain-of-function mutation in the gene for proprotein convertase subtilisin/kexin type-9 (PCSK9) (Kullo, n.d.).
2.2. autosomal dominant inheritance (McCance & Huether, 2015).
2.3. 1 in 500 people is a heterozygote (McCance & Huether, 2015).
3. Treatments
3.1. For FH heterozygotes: dietary restrictions liked reduced intake of saturated fats. Accompanied by bile acid-absorbing resins, such as cholestyramine, along with statin class of drugs, such as simvastatin (McCance & Huether, 2015).
3.2. For FH homozygotes: plasma exchange every 1 to 2 weeks, combined with with drug therapy. Liver transplant is a another but limited option (McCance & Huether, 2015).
4. Causative Factors
4.1. Mostly caused by a reduction in the number of LDL receptors on cell surfaces. Due to the lack of these receptors cellular cholesterol uptake is reduced and circulating cholesterol levels increase (McCance & Huether, 2015).
4.2. Homozygotes have few or no LDL receptors (McCance & Huether, 2015).
5. Risk Factors
5.1. More often seen earlier in males than females
5.2. Data suggested that 75% of men with FH developed CAD and 50% died of a myocardial infarction by age 60 (McCance & Huether, 2015).
5.3. In women the percentages were lower 45% and 15% respectively (McCance & Huether, 2015).
6. Diagnostic Tests
6.1. Can be diagnosed both clinically and genetically
6.1.1. A clinical diagnosis can be made through a lipid test to measure LDL levels, a physical exam and a family history (Familial Hypercholesterolemia, n.d.)
6.1.2. A genetic diagnosis can be made by testing for the three genetic mutations responsible for this disease (Familial Hypercholesterolemia, n.d.).