Familial Hyperchylomicronemia

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 chylomicrons → elevated 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.