What Is Tangier Disease?

Child and doctor
Cathy Yeulet, istockphoto

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 begin to 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
  • Enlarged lymph nodes
  • Gastrointestinal symptom, such as diarrhea and abdominal pain
  • 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 circulating in the blood. Although these individuals usually experience very mild to no symptoms, they are also at risk for premature cardiovascular disease due to the increased risk of developing atherosclerosis. Additionally, individuals diagnosed with this disease may pass this medical condition along to their children.

 

How Is Tangier Disease Diagnosed?

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 levels less than 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.

In order Tangier disease to be diagnosed, a physician will examine the results of the lipid panel and consider the signs and symptoms experienced by the individual.

Having a family history of the disease will also be taken into account.

 

How Is Tangier Disease Treated?

Because of the rarity of this disease, there are currently no treatments available for this condition. Medications that boost HDL cholesterol – both approved and experimental – do not appear to increase HDL levels in individuals with Tangier disease. Following a healthy diet that is low in saturated fat is recommended. Surgeries may be necessary based upon the symptoms experienced by the individual.

 

Sources:

Pisciotta L, Bocchi L, Candini C, et al. Severe HDL deficiency due to novel defects in the ABCA1 transporter. J Intern Med 2009 Mar; 265 (3): 359–72

Puntoni M, Francesco S, Bigazzi F, Sampietro T. Tangier disease: epidemiology, pathophysiology, and management. Am J Cardiovasc Drugs 2012: 12: 303-311
Schaefer EJ, Santos RD. Chapter 135. Xanthomatoses and Lipoprotein Disorders. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K. eds. Fitzpatrick's Dermatology in General Medicine, 8eNew York, NY: McGraw-Hill; 2012

Malloy MJ, Kane JP. Chapter 19. Disorders of Lipoprotein Metabolism. In:Gardner DG, Shoback D. eds. Greenspan’s Basic & Clinical Endocrinology, 9e.New York, NY: McGraw-Hill; 2011.

Continue Reading