Tangier disease is associated with ABCA1 mutation and very low HDL. Which condition is this?

• A. Abetalipoproteinemia
• B. Hypobetalipoproteinemia
• C. Tangier disease
• D. Hypoalphalipoproteinemia

Answer: (C)

Extremely low HDL due to an ABCA1 mutation points directly to Tangier disease. ABCA1 is the transporter that pumps cholesterol and phospholipids out of cells to apolipoprotein A-I, forming nascent HDL particles. When ABCA1 is defective, cholesterol efflux is impaired, so HDL particles are not formed properly and circulating HDL levels become very low. This genetic HDL deficiency is the hallmark of Tangier disease, with clinical clues such as orange-toned tonsils from lipid-laden macrophages, along with hepatosplenomegaly and neuropathy in some cases. The other conditions involve different defects: abetalipoproteinemia results from inability to assemble apoB-containing lipoproteins with fat malabsorption; hypobetalipoproteinemia has reduced apoB-containing lipoproteins but not due to ABCA1 dysfunction; hypoalphalipoproteinemia is a broad term for low HDL from various causes.