ABC1: connecting yellow tonsils, neuropathy, and very low HDL

In 1960, the most common surgical procedure performed on children was tonsillectomy. During one such routine operation, an astute physician recognized that the tonsils of his 5-year-old patient from Tangier Island were anything but ordinary (1). The tonsils were strikingly large, lobulated, and lemoncolored. The tonsils of the patient’s sister were similarly abnormal in appearance and had a 50- to 100-fold elevated content of cholesteryl ester. The siblings also shared another remarkable trait: both had extremely low plasma levels of HDL cholesterol (HDL-C). These children were the index cases of Tangier disease, a genetic disorder characterized by an abnormal plasma lipoprotein profile — virtual absence of HDL-C, reduced levels of LDL cholesterol (LDL-C) with mildly or moderately elevated triglycerides, and