Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Tangier Disease (TGD) [E78.6]

OMIM numbers: 205400, 600046 (ABCA1)

Dr. med. Hanns-Georg Klein

Scientific Background

Tangier disease is a rare autosomal recessive disorder of the metabolism of high-density lipoproteins (HDL) and is characterized by absence of mature HDL particles in the plasma and lipid deposition in various parenchymal organs. Characteristics include orange-colored, hyperplastic tonsils, splenomegaly and recurring neuropathies. Tangier patients have moderately increased risk of cardiovascular diseases.

The disease is caused by mutations in the ABCA1 gene (ATP-binding cassette transporter 1), a membrane protein, which is involved in the efflux of cholesterol and phospholipids from cells. The malfunctioning of ABCA1 causes nascent HDL particles to absorb cholesterol and phospholipids insufficiently from peripheral cells and are metabolized rapidly. Other monogenic diseases that lead to defective maturation of HDL particles and are therefore accompanied by HDL deficiency (hypoalphalipoproteinemia) (HDL-C < 10 mg/dl) are lecithin-cholesterol acyltransferase (LCAT) deficiency, partial LCAT deficiency (Fish Eye Disease) and apolipoprotein A-I (Apo A-I)-deficiency. Moreover, apo A-I deficiency has been associated with increased risk for CHD.