What Is Tangier Disease?

Tangier Disease Is Inherited, Resulting in Very Low HDL Levels

Tangier disease, also known as familial alpha lipoprotein deficiency, is an extremely rare, inherited condition that was first described in a child on Tangier Island, an island located off of the coast of Virginia. It is characterized by very low HDL cholesterol levels due to a mutation in a gene called ABCA1. This gene codes for a protein that helps get rid of excess cholesterol from inside the cell. When this protein is working properly, cholesterol is shuttled outside of the cell and binds to apolipoprotein A. This forms HDL, or “good” cholesterol, which will travel to the liver so that cholesterol can be recycled. Without this protein, cholesterol will remain inside of the cells and accumulate.

Symptoms of Tangier Disease

Tangier disease is usually noted in childhood and can range from very mild to severe. Individuals who are homozygous for this condition have mutations in both copies of the ABCA1 gene that codes for the protein and have virtually no HDL cholesterol circulating in the blood. These individuals will also have other symptoms as a result of cholesterol accumulation within various cells in the body, including:

• Neurological abnormalities (including peripheral neuropathy, decreased strength, loss of pain or heat sensation, muscle pain)
• Clouding of the cornea
• Abdominal pain, diarrhea
• Appearance or yellow patches on the intestinal mucosa, including the rectum
• Enlarged, yellow-orange tonsils
• Enlarged liver
• Enlarged spleen
• Premature cardiovascular disease

Heterozygous individuals, on the other hand, only have one copy of the mutated gene. They also have roughly half of the normal amount of HDL in the blood. Although these individuals usually experience very mild to no symptoms, they are also at risk for premature cardiovascular disease. Additionally, these individuals can pass this condition on to their children.

How Is Tangier Disease Diagnosed?

A lipid panel will be performed to examine the levels of cholesterol circulating in the blood. A cholesterol test would typically reveal the following findings:

• HDL cholesterol < 5 mg/dL in homozygous individuals
• HDL cholesterol between 5 and 30 mg/dL in heterozygous individuals
• Low total cholesterol levels (ranging between 38 and 112 mg/dL)
• Normal or elevated triglycerides (ranging between 116 and 332 mg/dL)

Levels of apolipoprotein A may also be low to nonexistent. Based upon an abnormal lipid panel, as well as the symptoms experienced by the individual, a diagnosis of Tangier disease will be made.

How Is Tangier Disease Treated?

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.

_Sources:

Brooks-Wilson A, Marcil M, Clee SM et al. Mutations in ABCA1 in Tangier disease and familial high-density lipoprotein deficiency. Nature Genetics 1999;22:336-345.

Fauci AC, Kasper DL, Longo DL et al. Harrison’s Principles of Internal Medicine. 17th edition, 2008.

Rudolph CD, Rudolph A, Hofstetter M, et al. Rudolph’s Pediatrics. 21st edition, 2003.