Tangier disease.
Tangier disease is a rare autosomal recessive disorder characterized by absence of plasma high-density lipoproteins (HDL), cholesterol ester accumulation in macrophages, progressive neuropathy and atherosclerosis. Known by synonyms such as an-a-lipoproteinemia, a-High-Density Lipoprotein Deficiency, alphalipoproteinemia, and Familial Alpha-Lipoprotein Deficiency, Tangier disease is caused by a defect in chromosome 9q31 affecting the gene product ATP binding cassette transporter-1 (ABC-1). The ABC-1 protein controls a cellular pathway that secretes cholesterol and phospholipids to lipid-poor apolipoproteins. The inability of the apolipoproteins to acquire cellular lipids leads to their rapid degradation and an over-accumulation of cholesterol in macrophages.
The disorder has been found among inhabitant of Tangier Island in Chesapeake Bay, most of whom are descendants of the first settlers of 1686. Other affected families have been found in Missouri, Kentucky, and Europe.
Clinically, enlarged orange-yellow tonsils, hepatosplenomegaly, enlarged lymph nodes, and premature coronary artery disease with an increased risk of myocardial infarction characterize Tangier's disease. In fact, the combination of enlarged orange-yellow tonsils and low plasma cholesterol is considered pathognomonic of the disease. In addition, sensory neuropathy such as slowly progressive pain and temperature loss, facial diplegia, and muscle wasting of the hands are common. Patient's serum displays hypocholesterolemia, markedly reduced high-density lipoproteins, and high triglycerides. No specific treatment is available.
Histologically, the tonsils and lymph nodes are characterized by prominent accumulations of clear, foamy xanthoma cells (macrophages) containing an accrual of cholesterol esters. The xanthoma cells tend to present in the parafollicular areas, though some may gather in the follicles as well. These cells may also be identified in biopsies of the skin, bone marrow, or rectum. Accumulation of cholesterol esters may also occur in Schwann cells and non-vascular smooth muscle, presenting as vacuolization of the affected cell.