The pathology of Tangier disease. A light and electron microscopic study.

Tangier disease (deficiency of high density plasma lipoproteins) is characterized clinically by: low levels of plasma cholesterol; enlarged, orange-yellow to yellow-gray tonsils and, frequently, peripheral neuropathy. Histologic and ultrastructural studies were made of various tissues from 5 patients with Tangier disease, and comparisons were made of these findings with those in the 12 other patients thus far known to have this disease. Deposits of cholesteryl esters were found in: reticuloendothelial cells (foam cells) in tonsils, bone marrow, skin and jejunal submucosa; Schwann cells in peripheral nerves and myenteric plexus; and in nonvascular smooth muscle cells. These deposits appeared electron lucent and intensely birefringent, varied from spherical to crystalline in shape, often were extensively confluent throughout large areas of cytoplasm, and were not limited by membranes. Certain foam cells in bone marrow also contained membrane-limited clusters of lipid particles resembling chylomicrons. The foam cells in Tangier disease differ morphologically from those in numerous lysosomal enzyme deficiency states, particularly Wolman's disease and cholesteryl ester stroage disease, and in proliferative diseases of the reticuloendothelial system in which cholesteryl esters also accumulate in abnormal histiocytes. Morphologic and biochemical data suggest several hypotheses to explain the accumulation of cholesteryl esters in tissues of patients with Tangier disease. Among these hypotheses, the most likely are considered to be the presence in plasma of abnormal lipoprotein particles that are subject to phagocytic removal by reticuloendothelial cells, and the failure of a process that normally removes locally synthesized cholesterol from cells to plasma. (Am J Pathol 78:101-158, 1975)