Tangier disease
Encyclopedia
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.
in the bloodstream, Apolipoprotein A1
(apoA1), combines with cholesterol and phospholipid
s. 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 in many body tissues. Reduced blood levels of high-density lipoproteins is sometimes described as hypoalphalipoproteinemia
.
People affected by this condition also have slightly elevated amounts of fat in the blood (mild hypertriglyceridemia
) and disturbances in nerve function (neuropathy). The tonsil
s 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.
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.
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, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.
High density lipoprotein
High-density lipoprotein is one of the five major groups of lipoproteins, which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, which enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream...
(HDL), often referred to as "good cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
," in the bloodstream.
Diagnosis
High-density lipoproteins are created when a proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
in the bloodstream, Apolipoprotein A1
Apolipoprotein A1
Apolipoprotein A-I is a protein that in humans is encoded by the APOA1 gene. It has a specific role in lipid metabolism.Apolipoprotein A-I is the major protein component of high density lipoprotein in plasma. Chylomicrons secreted from the intestinal enterocyte also contain ApoA1 but it is quickly...
(apoA1), combines with cholesterol and phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
s. 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
ABCA1
ATP-binding cassette transporter ABCA1 , also known as the cholesterol efflux regulatory protein is a protein which in humans is encoded by the ABCA1 gene...
transporter. People with Tangier disease have defective ABCA1
ABCA1
ATP-binding cassette transporter ABCA1 , also known as the cholesterol efflux regulatory protein is a protein which in humans is encoded by the ABCA1 gene...
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
Hypoalphalipoproteinemia
Hypoalphalipoproteinemia is a high-density lipoprotein deficiency, inherited in an autosomal dominant manner.It can be associated with LDL receptor.Associated regions and genes include:Niacin is sometimes prescribed to raise HDL levels....
.
People affected by this condition also have slightly elevated amounts of fat in the blood (mild hypertriglyceridemia
Hypertriglyceridemia
In medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia . It can also lead to pancreatitis in excessive concentrations In medicine,...
) and disturbances in nerve function (neuropathy). The tonsil
Tonsil
Palatine tonsils, occasionally called the faucial tonsils, are the tonsils that can be seen on the left and right sides at the back of the throat....
s are visibly affected by this disorder; they frequently appear orange or yellow and are extremely enlarged. Affected people often develop premature atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, which is characterized by fatty deposits and scar-like tissue lining the arteries. Other signs of this condition may include an enlarged spleen (splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
), an enlarged liver (hepatomegaly
Hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
), clouding of the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
, and early-onset cardiovascular 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
Virginia
The Commonwealth of Virginia , is a U.S. state on the Atlantic Coast of the Southern United States. Virginia is nicknamed the "Old Dominion" and sometimes the "Mother of Presidents" after the eight U.S. presidents born there...
, but has now been identified in people from many different countries.
Genetics
ABCA1
ATP-binding cassette transporter ABCA1 , also known as the cholesterol efflux regulatory protein is a protein which in humans is encoded by the ABCA1 gene...
transporter. These mutations prevent the ABCA1
ABCA1
ATP-binding cassette transporter ABCA1 , also known as the cholesterol efflux regulatory protein is a protein which in humans is encoded by the ABCA1 gene...
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, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.
External links
- http://www-personal.umd.umich.edu/~jcthomas/JCTHOMAS/1997%20Case%20Studies/J.%20Newman1.html