Tangier Disease Health Article

Definition

Tangier disease is a rare autosomal recessive condition characterized by low levels of high density lipoprotein cholesterol (HDL-C)in the blood, accumulation of cholesterol in many organs of the body, and an increased risk of arteriosclerosis.

Description

Donald Fredrickson was the first to discover Tangier disease. He described this condition in 1961 in a five-year-old boy from Tangier Island who had large, yellow-orange colored tonsils that were engorged with cholesterol. Subsequent tests on this boy and his sister found that they both had virtually no high density lipoprotein cholesterol (HDL-C) in their blood stream. Other symptoms of Tangier disease such as an enlarged spleen and liver, eye abnormalities, and neurological abnormalities were later discovered in others affected with this disease.

It was not until 1999 that the gene for Tangier disease, called the ABCA1 gene, was discovered. This gene is responsible for producing a protein that is involved in the pathway by which HDL removes cholesterol from the cells of the body and transports it to the liver where it is digested and removed from the body.

Cholesterol is transported through the body as part of lipoproteins. Low density lipoproteins (LDL) and high density lipoproteins (HDL) are two of the major cholesterol transporting lipoproteins. Cholesterol attached to LDL (LDL-C) is often called bad cholesterol since it can remain in the blood stream for a long time, and high levels of LDL-C can increase the risk of clogging of the arteries (arteriosclerosis) and heart disease. Cholesterol attached to HDL is often called good cholesterol since it does not stay in the blood stream for a long period of time, and high levels are associated with a low risk of arteriosclerosis.

Research as of 2001 suggests that the ABCA1 protein helps to transport cholesterol found in the cell to the surface of the cell where it joins with a protein called ApoA-1 and forms an HDL-C complex. The HDL-C complex transports the cholesterol to the liver where the cholesterol is digested and removed from the body. This process normally prevents an excess accumulation of cholesterol in the cells of the body and can help to protect against arteriosclerosis.

Genetic profile

Changes in the ABCA1 gene, such as those found in Tangier disease, cause the gene to produce abnormal ABCA1 protein. The abnormal ABCA1 protein is less able to transport cholesterol to the surface of the cell, which results in an accumulation of cholesterol in the cell. The accumulation of cholesterol in the cells of the body causes most of the symptoms associated with Tangier disease. The decreased efficiency in removing cholesterol from the body can lead to an increased accumulation of cholesterol in the blood vessels, which can lead to a slightly increased risk of arteriosclerosis and ultimately an increased risk of heart attacks and strokes. The ABCA1 protein defect also results in decreased amounts of cholesterol available on the surface of the cell to bind to ApoA-1 and decreased cholesterol available to form HDL-C. This in turn results in the rapid degradation of ApoA-1 and reduced levels of ApoA-1 and HDL-C in the bloodstream. It also leads to lower levels of LDL-C in the blood.

The ABCA1 gene is found on chromosome 9. Since we inherit one chromosome 9 from our mother and one chromosome 9 from our father, we also inherit two ABCA1 genes. People with Tangier disease have inherited one changed ABCA1 gene from their father and one changed ABCA1 gene from their mother, making Tangier disease an autosomal recessive condition.

Parents who have a child with Tangier disease are called carriers, since they each possess one changed ABCA1 gene and one unchanged ABCA1 gene. Carriers for Tangier disease do not have any of the symptoms associated with the disease, except for increased levels of HDL-C in their blood stream and a slightly increased risk of arteriosclerosis. The degree of risk of arteriosclerosis is unknown, and is dependent on other genetic and environmental factors, such as diet. Each child born to parents who are both carriers of Tangier disease has a 25% chance of having Tangier disease, a 50% chance of being a carrier, and a 25% chance of being neither a carrier nor affected with Tangier disease.

Demographics

Tangier disease is a very rare disorder with less than 100 cases diagnosed worldwide. Tangier disease affects both males and females.