NCBI Bookshelf. Genes and Disease [Internet]. Tangier disease TD is a genetic disorder of cholesterol transport named for the secluded island of Tangier, located off the coast of Virginia. TD was first identified in a five-year-old inhabitant of the island who had characteristic orange tonsils, very low levels of high density lipoprotein HDL or 'good cholesterol', and an enlarged liver and spleen. ABC1 codes for a protein that helps rid cells of excess cholesterol. This cholesterol is then picked up by HDL particles in the blood and carried to the liver, which processes the cholesterol to be reused in cells throughout the body.
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Tangier disease or hypoalphalipoproteinemia is an extremely 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. The disorder was originally discovered on Tangier Island off the coast of Virginia , but has now been identified in people from many different countries.
Individuals that are homozygotes for Tangier's disease develop various cholesterol ester depositions. The cholesterol esters may also be found in lymph nodes, bone marrow, the liver and spleen.
Due to the cholesterol ester depositions the tonsils may be enlarged. Hepatosplenomegaly enlarged liver and spleen is common. Neuropathy and cardiovascular disease are the most devastating developments caused by Tangier's disease. Mutations to 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. 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. This condition is inherited in an autosomal recessive pattern, meaning that for the phenotype to appear, two copies of the gene must be present in the genotype.
Tangier disease results in familial high-density lipoprotein deficiency. 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 are 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 and phospholipids in many body tissues, which can cause them to increase in size.
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 cornea , and early-onset cardiovascular disease. There are drugs that can increase serum HDL such as niacin or gemfibrozil. While these drugs are useful for patients with hyperlipidemia , Tangier's disease patients do not benefit from these pharmaceutical interventions. Therefore, the only current treatment modality for Tangier's disease is diet modification.
A low-fat diet can reduce some of the symptoms, especially those involving neuropathies. In , a five-year-old patient named Teddy Laird from Tangier Island, Virginia , presented with strikingly large and yellow-orange tonsils which were removed by armed forces physicians. After initial diagnosis with Niemann-Pick he was transferred to Dr. Louis Avioli at the National Cancer Institute. Donald Fredrickson, then head of the Molecular Disease Branch, became aware of the case and had a hunch that the original diagnosis was incorrect.
In , he traveled with Dr. Avioli to Tangier Island for further investigation. After finding the same symptom in Teddy's sister, an investigation revealed an extremely high number of foam cells cholesterol ester-laden macrophages in not only the tonsils, but also in a wide-range of tissues, including the bone marrow and spleen. During a second trip to the island, they found that the family had very low levels of HDL cholesterol, suggesting a genetic basis of the disease.
From Wikipedia, the free encyclopedia. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1.
Nat Genet ; Retrieved National Institute of Health. Homozygous Tangier disease and cardiovascular disease. Atherosclerosis ; August Genetics Home Reference. ICD - 10 : E Orphanet : Inborn error of lipid metabolism : dyslipidemia E78 , Lecithin cholesterol acyltransferase deficiency Tangier disease. Abetalipoproteinemia Apolipoprotein B deficiency Chylomicron retention disease. Barraquer—Simons syndrome. Genetic disorder , membrane: ABC-transporter disorders. Categories : Lipid metabolism disorders Autosomal recessive disorders Membrane transport protein disorders Skin conditions resulting from errors in metabolism Rare diseases.
Tangier disease or hypoalphalipoproteinemia is an extremely 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. The disorder was originally discovered on Tangier Island off the coast of Virginia , but has now been identified in people from many different countries. Individuals that are homozygotes for Tangier's disease develop various cholesterol ester depositions. The cholesterol esters may also be found in lymph nodes, bone marrow, the liver and spleen. Due to the cholesterol ester depositions the tonsils may be enlarged. Hepatosplenomegaly enlarged liver and spleen is common. Neuropathy and cardiovascular disease are the most devastating developments caused by Tangier's disease.
Enfermedad de Tangier
Gastric mucosa appearance in a patient with Tangier disease. Espinel, P. Olcoz and F. Izquierdo 1.