TD ( Tangier disease )

Tangier disease (TD) was first discovered in 1961 in two siblings living on Tangier Island.

Features:

• autosomal co-dominant condition is characterized in the homozygous state by the absence of HDL-cholesterol (HDL-C) from plasma, hepatosplenomegaly, peripheral neuropathy, a syringomyelia-like syndrome in the presence of lymphadenopathy, and frequently premature coronary artery disease (CAD)
• heterozygotes, HDL-C levels are about one-half those of normal individuals. It is the impaired cholesterol efflux from macrophages leads to the presence of foam cells throughout the body, which may explain the increased risk of coronary heart disease in some TD families
• due to functional mutations in ABCA1 (ATP-Binding Cassette Transporter 1) reduce the ability of ABCA1 to lipidate newly secreted Apo-AI in the liver and intestines, leading to rapid catabolism and clearance of Apo-A1 and low HDL levels (1)

Reference:

1. Jomard A and Osto E.High Density Lipoproteins: Metabolism, Function, and Therapeutic Potential. Front. Cardiovasc. Med. 2020;7:39. doi: 10.3389/fcvm.2020.00039