• Tangier disease is a rare autosomal recessive disorder characterized by complete absence of high-density lipoprotein (HDL) due to a mutation in the ABCA1 gene on chromosome 9. This prevents the transfer of cholesterol and phospholipids in cells onto nascent ApoA1 proteins, resulting in increased cholesterol levels in cells. In the homozygous state, patients present with low or undetectable levels of plasma HDL cholesterol, hepatosplenomegaly, peripheral neuropathy, orange tonsils, and premature coronary disease.
• In normal cells, the ABCA1 protein enables cholesterol to exit the cell, upon which it combines with ApoA1 to form HDL particles. The small amount of HDL that is present in patients with this disorder differs qualitatively from normal HDL.
• ApoA1 is found on HDL particles, and ApoB is found on very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles.
• Lipoprotein lipase deficiency is a rare, autosomal recessive disorder that presents in childhood with abdominal pain and pancreatitis. Defective or absent lipoprotein lipase creates an inability to clear chylomicrons, creating the classic “type 1” chylomicronemia syndrome.
• Patients with lipoprotein lipase deficiency do not develop premature coronary artery disease (CAD), implying that chylomicrons themselves are not atherogenic. Treatment with a low-fat diet to reduce chylomicron input is effective, fat-soluble vitamins should be supplemented, and drug therapy can be considered to lower endogenous VLDL production.