USMLE

Familial Hyperchylomicronemia

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

Summary

Familial hyperchylomicronemia, also known as type I hyperlipoproteinemia, is an autosomal recessive disorder characterized by high levels of chylomicrons. It is caused by homozygous mutations in lipoprotein lipase or its cofactor Apo C-II, which together normally cleave and release the chylomicrons’ triglyceride contents. Since chylomicrons carry triglycerides, hypertriglyceridemia is therefore a hallmark of the disease. High triglyceride levels are also a common cause of pancreatitis, which therefore may also be seen. Other findings include xanthomas, hepatosplenomegaly, and a creamy supernatant layer in blood samples.

Key Points

  • Familial hyperchylomicronemia
    • Also known as type I hyperlipoproteinemia
    • Genetics
      • Autosomal recessive
        • This disease is really rare, which is at least in part due to this
      • Caused by homozygous defects in either:
        • Lipoprotein lipase
        • Apo C-II
      • I like to think of this disease as an extreme form of familial hypertriglyceridemia, which can be caused by heterozygous mutations in lipoprotein lipase / Apo C-II
    • Labs
      • Elevated chylomicronselevated triglycerides
      • High cholesterol
        • Chylomicrons primarily contain triglycerides, but they also carry dietary cholesterol and fat-soluble vitamins
        • Knowing this won't really get you any questions right, though, and this isn't the main point of the disease
    • Clinical Features
      • Pancreatitis
        • Caused by increased triglycerides
      • Hepatosplenomegaly
        • Familial hyperchylomicronemia is characterized by so much fat / triglycerides that there is even a creamy fat layer in the blood. It should come as no surprise that there’s also fatty infiltration of the organs.
      • Xanthomas (eruptive / pruritic)
      • Creamy layer in supernatant
        • There’s so much fat / triglycerides in the blood
      • No increased risk of atherosclerosis
        • Chylomicrons are primarily associated with triglycerides and not cholesterol. The other hyperlipoproteinemias that increase primarily cholesterol-rich lipoproteins are those that are most atherogenic.