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Tangier disease

Wednesday 21 April 2004

ABCA1 deficiency

WP

Tangier disease is a severe HDL deficiency syndrome characterized by accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis. People with Tangier disease have defective ABCA1 transporters resulting in a greatly reduced ability to transport cholesterol out of their cells.

Clinics

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.

Etiology

- mutations in ABCA1 gene

Physiopathology

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 in many body tissues.

Reduced blood levels of high-density lipoproteins is sometimes described as hypoalphalipoproteinemia.

References

- Oram JF. Molecular basis of cholesterol homeostasis: lessons from Tangier disease and ABCA1. Trends Mol Med. 2002 Apr;8(4):168-73. PMID: 11927274