Familial Hypertriglyceridemia

Summary

Familial hypertriglyceridemia, also known as type IV hyperlipoproteinemia, is an autosomal dominant disorder that is defined by an isolated elevation of VLDL. This may have a number of possible causes, such as a heterozygous LPL-inactivating mutation, a hepatic overproduction of VLDL, or a decrease in VLDL clearance. Since VLDL carries 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. Finally, the disease is often accompanied by insulin resistance.

Key Points

• Familial Hypertriglyceridemia
  • Also known as type IV hyperlipoproteinemia
  • Genetics
    • Autosomal dominant
      • This disease is fairly common
  • Pathophysiology
    • Possible causes:
      • Heterozygote for LPL-inactivating mutation
      • Hepatic overproduction of VLDL
      • Decreased removal of VLDL
  • Clinical Features
    • Elevated VLDL → elevated triglycerides
      • This is the definition of familial hypertriglyceridemia
      • Compare / contrast with familial hyperchylomicronemia, which is also characterized by elevated VLDL / triglycerides
    • Pancreatitis
      • Caused by increased triglycerides
    • Often accompanied by insulin resistance
      • You may get premature atherosclerosis because of this, but you shouldn’t think of this familial hypertriglyceridemia as one of the CVD hyperlipoproteinemias. Those are hyperlipoproteinemias types II and III.
    • No CVD / premature atherosclerosis
    • Turbid serum
      • Contrast against familial hyperchylomicronemia, in which the serum has a creamy layer
      • I like to think of familial hypertriglyceridemia as a less severe form of familial hyperchylomicronemia