Diagnostically, Tangier Disease has several clinical signs that have been observed in most of the approximately 40 affected individuals, worldwide. On the other hand, heterozygotes for the disease show approximately half the normal levels of HDL-C in blood plasma. Patients with Tangier Disease have a defect in cellular cholesterol and lipid removal, which results in near zero plasma levels of HDL and in massive tissue deposition of cholesterol esters. Impaired cholesterol efflux from macrophages leads to the presence of foam cells throughout the body, which may explain the increased risk of coronary artery disease in some Tangier Disease families. The ABC1 transporter plays a major role in cholesterol efflux by acting as the transporter of free cholesterol in and out of cells.
Surplus cholesterol is esterfied and stored in lipid droplets in the cytosol.
Removing cellular cholesterol requires active transport of free cholesterol out of the cell and onto HDL particles. In patients with Tangier Disease, the mutated form of ABC1 blocks cholesterol efflux from cells, leading to the intracellular accumulation of cholesterol esters. The result is an increase in the amounts of cholesterol ester storage in cells, most prominently in tissue with macrophages, such as those that exist in the tonsils and other lymphoid tissues. Rust et al. ABC1 expression is induced by cholesterol loading and cAMP treatment, and is reduced upon subsequent cholesterol removal by apolipoproteins.