Familial Hypercholesterolemia

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Familial Hypercholesterolemia af Mind Map: Familial Hypercholesterolemia

1. Genetic Details

1.1. One of the most common autosomal dominant disorders

1.1.1. Heterozygous FH Affects 1:500 individuals FH inherited from only 1 parent This person has a 1 in 2 chance to pass on the mutated gene to each of his/her children.

1.1.2. Homozygous FH Affects 1:1,000,000 individuals FH inherited from both parents (a much more severe form of FH) Each of this person's children will inherit one copy of the mutated gene and will have heterozygous FH

1.2. >90% of cases are caused by gene mutation located on chromosome number 19

1.2.1. Contains the information for a protein called LDL receptor that is responsible for clearing LDL from the blood stream

2. Pathophysiology

2.1. Majority of FH cases caused by a loss-of-function mutation in the LDL-receptor gene (LDL-R) on chromosome 19

2.1.1. Mutations in this gene reduce the clearance of LDL particles from the blood due to a decreased LDL-R activity, leading to high LDL-C levels

2.2. May be caused by a mutation in the gene encoding apolipoprotein B (APOB) on chromosome 2

2.3. Another defect is one encoding a member of the proprotein convertase family, PCSK9 on chromosome 1p32

2.3.1. Mutations in this gene can be associated with low or high LDL-C levels through different mechanisms affecting the recycling of LDL-R

3. Causative Factors

3.1. Inherited in an autosomal dominant manner

4. Diagnostic Tests

4.1. Physical Examination

4.2. Blood testing of cholesterol levels

4.3. Studies of heart function

4.4. Genetic testing

5. Common Findings

5.1. Heterozygous FH: High levels of total cholesterol (usually >300mg/dl) and LDL cholesterol (usually >200mg/dl)

5.2. Homozygous FH: Extremely high levels of total cholesterol usually >600mg/dl

5.3. A strong family history of high levels of total and LDL cholesterol and/or early heart attack

5.4. Xanthomas (waxy deposits of cholesterol in the skin or tendons)

5.5. Xanthelasmas (cholesterol deposits in the eyelids)

5.6. Corneal arcus (cholesterol deposit around the cornea of the eye)

6. Treatments

6.1. Diet - reduce saturated fat, trans fat, cholesterol

6.2. Weight Loss

6.3. Exercise

6.4. Medications (usually necessary in combination to treat FH)

6.4.1. Statins

6.4.2. Bile acid sequestrant resins

6.4.3. Ezetemibe

6.4.4. Nicotinic acid

6.4.5. PCSK9 inhibitor

6.5. LDL apheresis (usually necessary only for homozygous FH)

6.6. Liver transplant

7. References

7.1. Alonso, R., Mata, P., Zambón, D., Mata, N., & Fuentes-Jiménez, F. (2013). Early diagnosis and treatment of familial hypercholesterolemia: Improving patient outcomes. Expert Review of Cardiovascular Therapy, 11(3), 327-42. doi:Early diagnosis and treatment of familial hypercholesterolemia: improving patient outcomes

7.2. McCance, K. & Huether, S. (2014). Pathophysiology. The biologic basis for disease in adults and children. St. Louis, MO: Elsevier.

7.3. Sniderman, A. D., Tsimikas, S., & Fazio, S. (2014). The severe hypercholesterolemia phenotype. Journal of the American College of Cardiology, 63(19), 1935-1947. doi:Elsevier: Article Locator

8. Risks

8.1. An important cause of heart disease

8.1.1. 75% of mean with FH develop coronary disease and 50% had a fatal MI by 60 years old

8.1.2. 45% of women with FH develop coronary disease and 15% had a fatal MI by 60 years old