Tangier disease: Difference between revisions

Jump to navigation Jump to search
Line 12: Line 12:


==Pathophysiology==
==Pathophysiology==
Tangier disease is a disorder of lipid metabolism where cholesterol efflux from reticulo-endothelial cells is impaired resulting in absent to severely decreased HDL. Cholesterol esters accumulates in macrophages which leads deposition of foam cells in several tissues.
Tangier disease is a disorder of [[lipid metabolism]] where cholesterol efflux from [[reticulo-endothelial]] cells is impaired resulting in absent to severely decreased HDL. [[High-density lipoproteins]] are created when a protein in the bloodstream, [[apolipoprotein A1]] ([[apoA1]]), combines with [[cholesterol]] and phospholipids.  Cholesterol and phospholipids used to form HDL originate from inside the cells, [[ABCA1]] transporter is responsible for transporting them out into blood.  Defective [[ABCA1]] transporter in Tangier disease results in cholesterol esters accumulation in macrophages which leads deposition of [[foam cells]] in several tissues like spleen, bone marrow and liver.<ref name="Bodzioch-1999">{{Cite journal  | last1 = Bodzioch | first1 = M. | last2 = Orsó | first2 = E. | last3 = Klucken | first3 = J. | last4 = Langmann | first4 = T. | last5 = Böttcher | first5 = A. | last6 = Diederich | first6 = W. | last7 = Drobnik | first7 = W. | last8 = Barlage | first8 = S. | last9 = Büchler | first9 = C. | title = The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. | journal = Nat Genet | volume = 22 | issue = 4 | pages = 347-51 | month = Aug | year = 1999 | doi = 10.1038/11914 | PMID = 10431237 }}</ref>
 
 


[[High-density lipoproteins]] are created when a protein in the bloodstream, [[apolipoprotein A1]] ([[apoA1]]), combines with [[cholesterol]] and phospholipids.  The cholesterol and phospholipids used to form HDL originate from inside cells but is transported out of the cell into the blood via the [[ABCA1]] transporter.  People with Tangier disease have defective [[ABCA1]] transporters resulting in a greatly reduced ability to transport cholesterol out of their cells, which leads to an accumulation of cholesterol in many body tissues.  Reduced blood levels of high-density lipoproteins is sometimes described as [[hypoalphalipoproteinemia]].


===Genetics===
===Genetics===

Revision as of 15:34, 11 September 2013

WikiDoc Resources for Tangier disease

Articles

Most recent articles on Tangier disease

Most cited articles on Tangier disease

Review articles on Tangier disease

Articles on Tangier disease in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Tangier disease

Images of Tangier disease

Photos of Tangier disease

Podcasts & MP3s on Tangier disease

Videos on Tangier disease

Evidence Based Medicine

Cochrane Collaboration on Tangier disease

Bandolier on Tangier disease

TRIP on Tangier disease

Clinical Trials

Ongoing Trials on Tangier disease at Clinical Trials.gov

Trial results on Tangier disease

Clinical Trials on Tangier disease at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Tangier disease

NICE Guidance on Tangier disease

NHS PRODIGY Guidance

FDA on Tangier disease

CDC on Tangier disease

Books

Books on Tangier disease

News

Tangier disease in the news

Be alerted to news on Tangier disease

News trends on Tangier disease

Commentary

Blogs on Tangier disease

Definitions

Definitions of Tangier disease

Patient Resources / Community

Patient resources on Tangier disease

Discussion groups on Tangier disease

Patient Handouts on Tangier disease

Directions to Hospitals Treating Tangier disease

Risk calculators and risk factors for Tangier disease

Healthcare Provider Resources

Symptoms of Tangier disease

Causes & Risk Factors for Tangier disease

Diagnostic studies for Tangier disease

Treatment of Tangier disease

Continuing Medical Education (CME)

CME Programs on Tangier disease

International

Tangier disease en Espanol

Tangier disease en Francais

Business

Tangier disease in the Marketplace

Patents on Tangier disease

Experimental / Informatics

List of terms related to Tangier disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Twinkle Singh, M.B.B.S. [3]

Synonyms and keywords: Familial alphalipoprotein deficiency, HDL deficiency - familial, high density lipoprotein deficiency, analphalipoproteinaemia, high density lipoprotein deficiency - type 1, high density lipoprotein deficiency - Tangier type

Overview

Tangier disease is a rare autosomal recessive disorder characterised by severely decreased high-density lipoprotein (HDL), often referred to as "good cholesterol" in the bloodstream, caused by defective cholesterol efflux from macrophages. It manifests with enlarged and orange coloured tonsils, hepatomegaly, splenomegaly, peripheral neuropathy and vision changes.

Historical Perspective

Tangier disease (TD) is named after Tangier Island, Virginia. In 1959 a five year old patient named Teddy Laird from that island, presented with strikingly large and yellow-orange tonsils, which were removed. Initially it was diagnosed as Niemann-Pick disease but a further investigation revealed an extremely high number of cholesterol filled macrophages (foam cells) in several other tissues, which included bone marrow and spleen. Presence of similar symptoms in his sister and discovery of very low HDL cholesterol in both the sister and parents of Teddy led to establishment of genetic basis of the disease. Later on several other residents of the same island were found to have markedly reduced HDL. Since then only 100 cases of Tangier disease have been diagnosed.

Pathophysiology

Tangier disease is a disorder of lipid metabolism where cholesterol efflux from reticulo-endothelial cells is impaired resulting in absent to severely decreased HDL. High-density lipoproteins are created when a protein in the bloodstream, apolipoprotein A1 (apoA1), combines with cholesterol and phospholipids. Cholesterol and phospholipids used to form HDL originate from inside the cells, ABCA1 transporter is responsible for transporting them out into blood. Defective ABCA1 transporter in Tangier disease results in cholesterol esters accumulation in macrophages which leads deposition of foam cells in several tissues like spleen, bone marrow and liver.[1]



Genetics

File:Autorecessive.svg

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.

Mutations in the chromosome 9q31 lead to a defective ABCA1 transporter. 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 (CAD).

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.




Epidemiology and Demographics

  • 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.

Natural History, Complications and Prognosis

Diagnosis

History

  • History of similar complaints in any of the family members should be inquired.

Symptoms

Physical Examination

Eye

Diffuse hazy opacity of the right cornea in the patient with Tangier disease.

Throat

  • Enlarged tonsils that appear orange or yellow.

Abdomen

Laboratory Findings

References

  1. Bodzioch, M.; Orsó, E.; Klucken, J.; Langmann, T.; Böttcher, A.; Diederich, W.; Drobnik, W.; Barlage, S.; Büchler, C. (1999). "The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease". Nat Genet. 22 (4): 347–51. doi:10.1038/11914. PMID 10431237. Unknown parameter |month= ignored (help)

External links

Template:Lipidemias

Template:WH Template:WS