Which are the causes of Tangier Disease?

Tangier Disease, also known as Tangier's disease or familial high-density lipoprotein (HDL) deficiency, is a rare genetic disorder that affects the body's ability to transport cholesterol and other lipids. It was first discovered in the 1960s on Tangier Island in the Chesapeake Bay, hence the name.

The primary cause of Tangier Disease is a mutation in the ABCA1 gene. This gene provides instructions for producing a protein that plays a crucial role in the formation of HDL, commonly referred to as "good cholesterol." HDL helps remove excess cholesterol from cells and transports it to the liver for disposal. However, in individuals with Tangier Disease, the ABCA1 gene mutation impairs the production or function of this protein, leading to a deficiency of functional HDL particles.

As a result of this genetic mutation, Tangier Disease leads to a significant reduction in HDL levels in the blood. HDL deficiency affects the body's ability to remove cholesterol from tissues, causing cholesterol to accumulate in various organs and tissues, including the tonsils, spleen, liver, lymph nodes, and peripheral nerves.

While the exact reasons behind the ABCA1 gene mutation are not fully understood, Tangier Disease is inherited in an autosomal recessive manner. This means that an affected individual must inherit two copies of the mutated gene, one from each parent, to develop the disease. If an individual inherits only one copy of the mutated gene, they become a carrier of the condition but typically do not experience symptoms.

It is important to note that Tangier Disease is an extremely rare disorder, with only a few hundred cases reported worldwide. The prevalence of the disease is higher in certain populations, such as those living on Tangier Island and in some communities in Sweden and the Netherlands, where the mutation is more common.

While Tangier Disease is primarily caused by the ABCA1 gene mutation, other factors may influence the severity and progression of the disease. These factors include lifestyle choices, such as diet and exercise, as well as other genetic variations that may interact with the ABCA1 mutation. Ongoing research aims to better understand these additional factors and their impact on the disease.