Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood. HDL transports cholesterol and certain fats called phospholipids from the body’s tissues to the liver, where they are removed from the blood.
Tangier disease is caused by mutations in the ABCA1 gene. These mutations prevent the release of cholesterol and phospholipids from cells. As a result, these substances accumulate within cells, causing certain body tissues to enlarge and the tonsils to acquire a yellowish-orange color. A buildup of cholesterol can be toxic to cells, leading to impaired cell function or cell death. In addition, the inability to transport cholesterol and phospholipids out of cells results in very low HDL levels, which increases the risk of cardiovascular disease.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Tangier disease is a rare disorder with approximately 100 cases identified worldwide. It is usually noted in childhood and can range from very mild to severe.
Signs and symptoms of Tangier disease include:
- Very low levels of HDL
- A slightly elevated amount of fat in the blood (mild hypertriglyceridemia)
- Disturbances in nerve function (neuropathy)
- Enlarged, orange-colored tonsils
- Enlarged spleen (splenomegaly)
- Enlarged liver (hepatomegaly)
- Clouding of the clear covering of the eye (corneal clouding)
- Type 2 diabetes
HDL is often referred to as “good cholesterol” because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. Because people with Tangier disease have very low levels of HDL, they have a moderately increased risk of cardiovascular disease.
Affected individuals often develop atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries.
Because of the rarity of this disease, there are currently no treatments available for this condition. Surgeries may be necessary based upon the symptoms experienced by the individual.