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Tangier disease

Reviewed June 2006

What is Tangier disease?

Tangier disease is a rare inherited disorder characterized by a severe reduction in the amount of high-density lipoprotein (HDL), often referred to as "good cholesterol," in the bloodstream. High-density lipoproteins are created when a type of protein in the bloodstream, apolipoprotein A1 (apoA1), picks up cholesterol from the cells. People with Tangier disease have a greatly reduced ability to transport cholesterol out of their cells, leading to a deficiency of high-density lipoproteins in the bloodstream and the accumulation of cholesterol in many body tissues. Reduced blood levels of high-density lipoproteins is sometimes described as hypolipoproteinemia.

People affected by this condition also have slightly elevated amounts of fat in the blood (mild hypertriglyceridemia) and disturbances in nerve function (neuropathy). The tonsils are visibly affected by this disorder; they frequently appear orange or yellow and are extremely enlarged. Affected people often develop premature atherosclerosis, which is characterized by fatty deposits and scar-like tissue lining the arteries. Other signs of this condition may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of the clear covering of the eye (cornea), and early-onset cardiovascular disease.

How common is Tangier disease?

Tangier disease is a rare disorder with approximately 50 cases identified worldwide. This disorder was originally discovered on Tangier Island off the coast of Virginia, but has now been identified in people from many different countries.

What genes are related to Tangier disease?

Mutations in the ABCA1 gene cause Tangier disease.

The ABCA1 gene provides instructions for making a protein that transports cholesterol and particular fats called phospholipids out of the cells. These mutations prevent the ABCA1 protein from effectively transporting cholesterol and phospholipids out of cells for pickup by ApoA1 in the bloodstream. This inability to transport cholesterol out of cells leads to a deficiency of high-density lipoproteins in the circulation, which is a risk factor for coronary artery disease. Additionally, the buildup of cholesterol in cells can be toxic, causing cell death or impaired function. These combined factors lead to the signs and symptoms of 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 treatment for Tangier disease?

You may find information on treatment or management of Tangier disease or some of its symptoms in the links below, particularly the links for MedlinePlus Encyclopedia, Educational resources, and Patient support.

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
    • Encyclopedia: HDL (http://www.nlm.nih.gov/medlineplus/ency/article/003496.htm)
    • Health Topic: Cholesterol (http://www.nlm.nih.gov/medlineplus/cholesterol.html)
    • Health Topic: Coronary Artery Disease (http://www.nlm.nih.gov/medlineplus/coronaryarterydisease.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)
  • Additional NIH Resources - National Institutes of Health
    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.237)
    • National Heart, Lung, and Blood Institute: Apolipoprotein Deficiency Research Study (http://patientrecruitment.nhlbi.nih.gov/LipidDisorders.aspx)
  • Educational resources - Information pages
    • Health on the Net Foundation (http://www.hon.ch/HONselect/RareDiseases/EN/C10.668.829.800.875.html)
    • Hypolipoproteinemias (Clinical Methods, third edition, 1990) (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cm.chapter.951#973)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=31150)
    • The Complex Regulation of Cholesterol Biosynthesis Takes Place at Several Levels (Biochemistry, 5th Edition, 2002) (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.3628)
    • The Human ATP-Binding Cassette (ABC) Transporter Superfamily (NCBI) (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mono_001&partid=31#A137)
    • The Merck Manual of Medical Information, Second Home Edition (http://www.merck.com/mmhe/sec12/ch157/ch157c.html)
  • Patient support - For patients and families
    • American Heart Association (http://www.americanheart.org/presenter.jhtml?identifier=1516)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Tangier%20Disease)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22Tangier+disease%22+OR+%22Hypolipoproteinemia%22+OR+%22Tangier+Disease%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Tangier+Disease[MAJR])+AND+(Tangier+disease[TIAB])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1800+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Familial Analphalipoproteinemia: Tangier Disease (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=122)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=205400)

What other names do people use for Tangier disease?

  • 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

See 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?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding Tangier disease?

apolipoprotein ; artery ; atherosclerosis ; autosomal ; autosomal recessive ; cardiovascular ; cell ; cholesterol ; cornea ; coronary ; coronary artery ; coronary artery disease ; deficiency ; enlarged spleen ; familial ; gene ; HDL ; high density lipoproteins ; hypertriglyceridemia ; hypolipoproteinemia ; lipoprotein ; mutation ; neuropathy ; protein ; recessive ; risk factors ; sign ; splenomegaly ; symptom ; tissue ; tonsil ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001 Jul;11(7):1156-66. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11435397)
  • Hobbs HH, Rader DJ. ABC1: connecting yellow tonsils, neuropathy, and very low HDL. J Clin Invest. 1999 Oct;104(8):1015-7. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10525038)
  • Knight BL. ATP-binding cassette transporter A1: regulation of cholesterol efflux. Biochem Soc Trans. 2004 Feb;32(Pt 1):124-7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14748729)
  • 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. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16611066)
  • Lawn RM, Wade DP, Garvin MR, Wang X, Schwartz K, Porter JG, Seilhamer JJ, Vaughan AM, Oram JF. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J Clin Invest. 1999 Oct;104(8):R25-31. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10525055)
  • 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16319881)
  • 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16235041)
  • Pajukanta P. Do DNA sequence variants in ABCA1 contribute to HDL cholesterol levels in the general population? J Clin Invest. 2004 Nov;114(9):1244-7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15520856)
  • 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15262183)
  • Scriver, Charles R; The metabolic & molecular bases of inherited disease; 8th ed.; New York : McGraw-Hill, c2001. p2053-2072.
  • 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16013195)
  • Stefkova J, Poledne R, Hubacek 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15209530)
  • Takahashi K, Kimura Y, Nagata K, Yamamoto A, Matsuo M, Ueda K. ABC proteins: key molecules for lipid homeostasis. Med Mol Morphol. 2005 Mar;38(1):2-12. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16158173)

 

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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2006
Published: January 12, 2009