Description
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. 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.
Additional signs and symptoms of Tangier disease include a slightly elevated amount of fat in the blood (mild hypertriglyceridemia); disturbances in nerve function (neuropathy); and enlarged, orange-colored tonsils. Affected individuals often develop atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. Other features of this condition may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of the outermost layer of the eye (corneal clouding), and type 2 diabetes.
Frequency
Tangier disease is a rare disorder, with approximately 100 cases identified worldwide. More cases are likely undiagnosed. This condition is named after an island off the coast of Virginia where the first affected individuals were identified.
Causes
Variants (also called mutations) in the ABCA1 gene cause Tangier disease. This gene provides instructions for making a protein that releases cholesterol and phospholipids from cells. These substances are used to make HDL. HDL then transports cholesterol and phospholipids to the liver.
Variants in the ABCA1 gene 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 a person's risk of cardiovascular disease. All these factors cause the signs and symptoms of Tangier disease.
Inheritance
Tangier disease is inherited in an autosomal recessive pattern
, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition; however, they may have a related condition called familial HDL deficiency.
Other Names for This Condition
- A-alphalipoprotein neuropathy
- Alpha high density lipoprotein deficiency disease
- Analphalipoproteinemia
- Cholesterol thesaurismosis
- Familial high density lipoprotein deficiency disease
- Familial hypoalphalipoproteinemia
- HDL lipoprotein deficiency disease
- Lipoprotein deficiency disease, HDL, familial
- Tangier disease neuropathy
- Tangier hereditary neuropathy
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Clinical Trials
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
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- Maxfield FR, Tabas I. Role of cholesterol and lipid organization in disease. Nature. 2005 Dec 1;438(7068):612-21. doi: 10.1038/nature04399. Citation on PubMed
- Nofer JR, Remaley AT. Tangier disease: still more questions than answers. Cell Mol Life Sci. 2005 Oct;62(19-20):2150-60. doi: 10.1007/s00018-005-5125-0. Citation on PubMed
- Probst MC, Thumann H, Aslanidis C, Langmann T, Buechler C, Patsch W, Baralle FE, Dallinga-Thie GM, Geisel J, Keller C, Menys VC, Schmitz G. Screening for functional sequence variations and mutations in ABCA1. Atherosclerosis. 2004 Aug;175(2):269-79. doi: 10.1016/j.atherosclerosis.2004.02.019. Citation on PubMed
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- Tang C, Oram JF. The cell cholesterol exporter ABCA1 as a protector from cardiovascular disease and diabetes. Biochim Biophys Acta. 2009 Jul;1791(7):563-72. doi: 10.1016/j.bbalip.2009.03.011. Epub 2009 Apr 1. Citation on PubMed
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