Snapshot A 12-year-old boy presents to the emergency department with chest pain after gym class. His parents note that he has been having increased episodes of difficulty catching his breath after exertion and has had previous episodes of chest pain on exertion. Upon physical exam yellow deposits are found on his heels and on his eyebrows. Based on clinical suspicion a LDL level is obtained and is found to be 480 mg/dL. He is referred to a geneticist for evaluation of deficiencies in LDL receptors and is prescribed a statin. Hyperlipoproteinemia Overview Type I hyperlipoproteinemia (hyperchylomicronemia) pathophysiology deficiency in lipoprotein lipase or apoC-II results in ↑↑↑↑ TGs, chylomicrons presentation eruptive xanthomas steatosis abdominal pain post-fat ingestion retinitis pigmentosa Type II hyperlipoproteinemia pathophysiology deficiency in LDL receptors type IIa (familial hypercholesterolemia) results in ↑↑↑↑ LDL >260 mg/dL see Cholesterol topic type IIb (familial combined hyperlipidemia) results in ↑↑↑↑ LDL, TGs, cholesterol presentation deposition of cholesterol in normal tissue xanthomas xanthelasma ↑↑ risk for coronary heart disease Type III hyperlipoproteinemia (familial dysbetalipoproteinemia) pathophysiology deficiency in apolipoprotein E remember: III lacks E results in ↑↑↑ in remnants (chylomicron/ IDL) apolipoprotein normally clears remnants (empties) presentation similar to type II hyperlipoproteinemia ↑↑ risk for coronary heart disease Type IV hyperlipoproteinemia (familial hypertriglyceridemia) pathophysiology ↓ removal or ↑ production of VLDL results in ↑↑↑ in VLDL presentation pancreatitis Type V hyperlipoproteinemia type I + type IV ↓ lipoprotein lipase + ↑ VLDL remember: 1+4=5 Acquired hypercholesterolemia obstructive jaundice oral contraceptives Acquired hypertriglyceridemia alcoholism renal failure diabetes mellitus Treatment for hyperlipoproteinemias dietary modifications (type I) statins (type II - IV) niacin (type II, IV, V) fibrates (type IIa, IV, V) bile acid sequestrants (type IIa) Hypolipoproteinemia Overview Abetalipoproteinemia AR pathophysiology due to mutations in the microsomal triglyceride transfer protein (MTTP) deficiency in apolipoprotein B-48 and B-100 remember: A (without) beta (B) ↓ chylomicrons (B-48), VLDL/LDL (B-100) presentation malabsorption of fat can enter enterocytes but cannot exit because it cannot be packaged for release in lipoproteins leads to histological appearance of fat droplets inside enterocytes ↓ vitamin E absorption ataxia hemolytic anemia with acanthocytes High Yield Remember that type I, IIa, and IV are the most common types of hyperlipoproteinemia I and IV present with pancreatitis, IIa presents with early symptoms of ACS Treat all types other than I with statins, niacin, and fibrates