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Tangier Disease is an inherited blood disorder involving decreased concentrations of fat compounds in the blood called high-density lipoproteins (sometimes called "good cholesterol"). Large amounts of these compounds may accumulate in certain organs of the body causing tissue discoloration. In later stages, these accumulations may cause organ enlargement and/or blood circulation problems.
Tangier Disease is a slowly progressive disorder initially characterized by enlarged orange or yellowish-gray tonsils. This same discoloration may be found in other parts of the throat and digestive system-particularly the rectum that is only 4 inches long and the end part of the large intestines. In time, the liver, spleen and lymph nodes may become enlarged. Brain dysfunction, loss of tendon reflexes and coronary artery disease may also occur. In some cases, small solid elevated skin lesions (papules) may also appear.
Tangier Disease is an autosomal recessive genetic disorder as explained below.
All human traits including classic genetic diseases are the product of the interaction of two genes for that condition, one gene that is received from the father and one gene of the similar type received from the mother.
In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will be symptom-free.
Couples in which both parents are carriers for a recessive disorder, the risk of transmitting the disease to the children of a couple is only 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Recently, scientists in several laboratories, including that of Dr. Michael Hayden at the University of British Columbia have successfully identified the gene that causes Tangier Disease. The gene, known as ABC1, controls the process of producing a protein that transports the "bad" cholesterol and other lipids out of cells while also raising the proportion of "good" cholesterol and other lipids which remain in the cell.
Cholesterol is a soft, waxy substance found among the lipids (fats) in the bloodstream and in all the cells in our body and essential in the formation of cell membranes, hormones and other functions Cholesterol and other fats can't dissolve in the blood and have to be transported to and from the cells by special carriers called lipoproteins. There are several kinds, but the ones to focus on are low-density lipoprotein (LDL) and high-density lipoprotein (HDL). About one-third to one-fourth of blood cholesterol is carried by HDL. HDL is also commonly called the "good" cholesterol because it removes cholesterol from the artery walls and disposes them through the liver, while LDL deposits cholesterol on the artery walls, causing the formation of a hard, thick substance called cholesterol plaque.
In Tangier Disease the protein that transports the "bad" cholesterol out of the cell is not functioning optimally or missing. This could lead to a decrease or even diminish the proportion of "good" cholesterol HDL inside the cells and lead to excessive lipid levels "fat" being carried in the blood stream and may get deposited in various organ of the body such liver, heart, spleen, lymph nodes and the brain.
Tangier disease is thought to be present at birth but without noticeable symptoms. It usually is diagnosed during later childhood or adulthood. Tangier disease was first identified in a five-year old boy native to a secluded island located at Chesapeake Bay, Maryland off the coast of Virginia. This disorder was first identified in the inbred population of Tangier Island and later in Missouri and Kentucky. However, it may possibly be spreading to other countries. Only fifty known cases in the world have been documented between 1967 and 2007, although the primary reason for this small number may be misdiagnosis and a low level of recognition of symptoms.
Acanthocytosis, also known as Bassen-Kornzweig Syndrome, is inherited as a recessive trait and can often be found in inbred populations. This disorder is marked by the absence of low density lipoproteins (LDL) and excretion of fat in stools (steatorrhea). Other features of Acanthocytosis may include abnormal red blood cells (acanthocytes), retinitis pigmentosa, ataxia and mental retardation. Absorption of fat is markedly impaired. Massive doses of Vitamins E and A may delay or retard the neurologic complications. (For more information choose Acanthocytosis","RP" and "ataxia" as your search terms in the Rare Disease Database.)
Treatment of Tangier Disease is symptomatic and supportive. Genetic counseling may be of benefit to families of patients with this disorder. Surgical removal of the spleen may become necessary in some cases if the spleen is enlarged.
This disease entry is based upon medical information available through October 1999. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.
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Mutations in Abc1in Tangier Disease and Familial High-Density Lipoprotein Deficiency: A. Brooks-Wilson, et al.; Nature Genet. 22: 336-345, 1999.
The Gene Encoding Atp-Binding Cassette Transporter 1 is Mutated in Tangier Disease: M. Bodzioch, et al.; Nature Genet. 22: 347-351, 1999.
Tangier Disease is Caused By Mutations in the Gene Encoding Atp-Binding Cassette Transporter 1: S. Rust, et al.; Nature Genet. 22:352-355, 1999.
Tangier Disease: A Disorder of Intracellular Membrane Traffic: G. Schmitz, et al.; Proc. Nat. Acad. Sci. 82: 6305-6309, 1985.
Tangier Disease. A Histological And Ultrastructural Study: P. Dechelotte, et al.; Pathol Res Pract (Oct. 1985, issue 180(4)). Pp. 424-430.
Neuropathy in Tangier Disease: A Clinicopathologic Study and a Review of the Literature: V. Pietrini et al.; Acta Neurol Scand. 72:495-505,1985
Japanese Adult Siblings With Tangier Disease And Statistical Analysis Of Reported Cases: K. Fujii, et al.; Tokai J Exp Clin Med (Dec. 1984, issue 9(5-6)). Pp.379-387.
Kolovou GD, Mikhailidis DP, Anagnostopoulou KK, Daskalapoulou SS, Cokkinos DV. Tangier diseases four decades of research: a reflection of the importance of HDL. Curr Med Chem. 2006;13(7):771-82.
Kaminski WE, Piehler A, Wenzel JJ. ABC A-subfamily transporters: structure, function and disease. Biochim Biophys Acta. 2006 May;1762 (5):510-24.
Nofer JR, Remaley AT. Tangier disease: still more questions than answers. Cell Mol Life Sci. 2005 Oct;62(19-20):2150-60.
Hovingh GK, de Groot E, van der Steeg W, Boekholdt SM, Hutten BA, Kuivenhoven JA, Kastelein JJ. Inherited disorders of HDL metabolism and atherosclerosis. Curr Opin Lipidol. 2005 Apr;16(2):139-45.
Miller M, Zhan M. Genetic determinants of low high-density lipoprotein cholesterol. Curr Opin Cardiol. 2004 Jul;19(4):380-4.
FROM THE INTERNET
Tangier disease. Genetic Home Reference. Last comprehensive review: June 2006.4pp
Tangier disease. Genes and Disease. nd. 2pp.
Report last updated: 2007/05/04 00:00:00 GMT+0