Reviewed March 2010
What is Tangier disease?
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 clear covering of the eye (corneal clouding), and type 2 diabetes.
How common is Tangier disease?
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.
What genes are related to Tangier disease?
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, which transports them to the liver.
Mutations 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 the risk of cardiovascular disease. These combined factors cause the signs and symptoms of Tangier disease.
Changes in this gene are associated with Tangier disease.
How do people inherit Tangier 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.
Where can I find information about diagnosis or management of Tangier disease?
These resources address the diagnosis or management of Tangier disease and may include treatment providers.
- Genetic Testing Registry: Tangier disease (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0039292)
- Lab Tests Online: HDL Cholesterol (http://labtestsonline.org/understanding/analytes/hdl/tab/glance)
You might also find information on the diagnosis or management of Tangier disease in
Educational resources (http://www.ghr.nlm.nih.gov/condition/tangier-disease/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/tangier-disease/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook.
Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
Where can I find additional information about Tangier disease?
You may find the following resources about Tangier disease helpful. These materials are written for the general public.
MedlinePlus - Health information
- Health Topic: Atherosclerosis (http://www.nlm.nih.gov/medlineplus/atherosclerosis.html)
- Health Topic: Cholesterol (http://www.nlm.nih.gov/medlineplus/cholesterol.html)
- Health Topic: Diabetes (http://www.nlm.nih.gov/medlineplus/diabetes.html)
- Health Topic: Heart Diseases (http://www.nlm.nih.gov/medlineplus/heartdiseases.html)
- Health Topic: Peripheral Nerve Disorders (http://www.nlm.nih.gov/medlineplus/peripheralnervedisorders.html)
- Health Topic: Vascular Diseases (http://www.nlm.nih.gov/medlineplus/vasculardiseases.html)
- Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/7731/resources/resources/1)
Educational resources - Information pages
- Children Living with Inherited Metabolic Diseases (CLIMB): Tangier Disease (http://www.climb.org.uk/IMD/Tango/TangierDisease.pdf)
- Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=31150)
Patient support - For patients and families
- American Heart Association (http://www.heart.org/HEARTORG/Conditions/Cholesterol/CholestrolATH_UCM_001089_SubHomePage.jsp)
- Children Living with Inherited Metabolic Diseases (CLIMB) (http://www.climb.org.uk/)
- National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/385/viewAbstract)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Tangier disease (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0039292)
- ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22Tangier%20disease%22%20OR%20%22Hypolipoproteinemia%22%20OR%20%22Tangier%20Disease%22)
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Tangier%20Disease%5BMAJR%5D)%20AND%20(Tangier%20disease%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/205400)
What other names do people use for Tangier disease?
- A-alphalipoprotein Neuropathy
- alpha High Density Lipoprotein Deficiency Disease
- 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
For more information about naming genetic conditions, see the Genetics Home Reference
Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide)
How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What if I still have specific questions about Tangier disease?
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
What glossary definitions help with understanding Tangier disease?
autosomal recessive ;
enlarged spleen ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Iatan I, Alrasadi K, Ruel I, Alwaili K, Genest J. Effect of ABCA1 mutations on risk for myocardial infarction. Curr Atheroscler Rep. 2008 Oct;10(5):413-26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18706283?dopt=Abstract)
- Kolovou GD, Mikhailidis DP, Anagnostopoulou KK, Daskalopoulou SS, Cokkinos DV. Tangier disease four decades of research: a reflection of the importance of HDL. Curr Med Chem. 2006;13(7):771-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16611066?dopt=Abstract)
- Koseki M, Matsuyama A, Nakatani K, Inagaki M, Nakaoka H, Kawase R, Yuasa-Kawase M, Tsubakio-Yamamoto K, Masuda D, Sandoval JC, Ohama T, Nakagawa-Toyama Y, Matsuura F, Nishida M, Ishigami M, Hirano K, Sakane N, Kumon Y, Suehiro T, Nakamura T, Shimomura I, Yamashita S. Impaired insulin secretion in four Tangier disease patients with ABCA1 mutations. J Atheroscler Thromb. 2009 Jun;16(3):292-6. Epub 2009 Jun 25. (http://www.ncbi.nlm.nih.gov/pubmed/19556721?dopt=Abstract)
- Maxfield FR, Tabas I. Role of cholesterol and lipid organization in disease. Nature. 2005 Dec 1;438(7068):612-21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16319881?dopt=Abstract)
- Nofer JR, Remaley AT. Tangier disease: still more questions than answers. Cell Mol Life Sci. 2005 Oct;62(19-20):2150-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16235041?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/15262183?dopt=Abstract)
- Soumian S, Albrecht C, Davies AH, Gibbs RG. ABCA1 and atherosclerosis. Vasc Med. 2005 May;10(2):109-19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16013195?dopt=Abstract)
- Stefková J, Poledne R, Hubácek JA. ATP-binding cassette (ABC) transporters in human metabolism and diseases. Physiol Res. 2004;53(3):235-43. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15209530?dopt=Abstract)
- Tall AR, Yvan-Charvet L, Terasaka N, Pagler T, Wang N. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab. 2008 May;7(5):365-75. doi: 10.1016/j.cmet.2008.03.001. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18460328?dopt=Abstract)
- 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19344785?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.