Tangier Disease

Etiology and Clinical Features

Tangier disease is an autosominal codominant disorder in which homozygotes have very low levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I (both <10 mg/dL), decreased low-density lipoprotein (LDL) cholesterol levels (about 40% of normal), and mild hypertriglyceridemia.

The disorder is caused by mutations in the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1).

Tangier disease was initially discovered almost half a century ago in families inhabiting Tangier Island in the Chesapeake Bay, but has since been found in other individuals.

Abnormalities in reverse cholesterol transport leading to storage of cholesterol esters in reticuloendothelial tissues produce the characteristic large orange tonsils as well as infiltration of other organs. The major neurologic manifestation is peripheral neuropathy, but the affected individuals also may have cardiovascular and cerebrovascular disease occurring prematurely or late in life.

    Adapted from: Maxfield & Tabas, Nature 2005; Serfaty-Lacrosniere et al., Atherosclerosis 1994.