Medicine & USMLE

Familial Hypercholesterolemia

  1. Chylomicron Metabolism
  2. VLDL Metabolism
  3. HDL Metabolism
  4. Abetalipoproteinemia
  5. Familial Hyperchylomicronemia
  6. Familial Hypercholesterolemia
  7. Familial Dysbetalipoproteinemia
  8. Familial Hypertriglyceridemia


Familial hypercholesterolemia, otherwise known as type II hyperlipoproteinemia, is an autosomal dominant disease that results in abnormally high levels of LDL in the body. This disease is usually caused by a defect in the LDL receptor, but it may also be caused by mutations in the LDL receptor’s ligand: apo B-100.

When LDL is unable to be cleared from the circulation, atherosclerosis is accelerated. Patients may therefore develop cardiovascular disease at extremely young ages. Other manifestations include corneal arcus and tendon xanthomas.

Key Points

  • Familial Hypercholesterolemia
    • Also known as type II hyperlipoproteinemia
    • Pathophysiology
      • Caused by:
        • LDL receptor mutations (more likely)
        • Apo B-100 mutations (less likely)
      • Leads to high LDL levels
        • Apo B-100 on LDL binds to the LDL receptor, which facilitates the uptake and clearance of the LDL particle; mutations in this step lead to reduced LDL clearance
        • LDL carries cholesterol, which is why the disease is called “hyper- CHOLESTEROL -emia”
    • Genetics
      • Autosomal dominant
        • Familial hypercholesterolemia is actually the most common autosomal dominant genetic disease
    • Types
      • Divided into two types based on whether or not triglycerides (i.e. VLDL) are also elevated
        • IIa: raised LDL / cholesterol
        • IIB: raised LDL / cholesterol AND VLDL / TGs
    • Clinical Features
      • Accelerated atherosclerosis
        • Patients May have myocardial infarction before age 20
          • A high percentage of patients with MI before 35 have mutations in the LDL receptor
        • Occurs because LDL donates lipids to atherosclerotic plaques
          • LDL cholesterol is “bad” cholesterol
      • Corneal arcus
        • This is a lipid ring around the cornea
      • Tendon xanthomas
        • e.g. Achilles tendon