Tangier disease

Tangier disease is a rare genetic metabolic disorder characterized by extremely low or almost absent levels of HDL (high-density lipoprotein) cholesterol in the blood.

HDL is responsible for transporting cholesterol and phospholipids from tissues to the liver for removal from the blood, which is why it is often called "good" cholesterol. The absence of HDL causes cholesterol to accumulate in various organs of the body, such as the skin, bone marrow, nerves, muscles, and rectal mucosa, and increases the risk of atherosclerosis (the buildup of cholesterol plaques and fats in the arteries).

People with Tangier disease have less than 5% of the normal levels of HDL in their blood.

Tangier disease is caused by a mutation in the ABCA1 gene, which is located on chromosome 9 (9q22-31).

It is a genetic disorder inherited in an autosomal recessive manner, meaning that a person must inherit the mutated gene from both parents to develop the disease.

Tangier disease is rare, with only about 200 cases reported worldwide. It appears to affect men and women equally.

The absence of HDL lipoproteins leads to the accumulation of cholesterol and phospholipids in various parts of the body, including the peripheral nerves, spleen, lymph nodes, liver, intestines, and cornea.

The most common symptoms include:

• Enlarged, yellowish tonsils.
• Orange-brown spots in the rectum due to cholesterol accumulation in the intestinal mucosa.
• Splenomegaly (enlarged spleen), which can cause hemolytic anemia and thrombocytopenia (low platelet count).
• Hepatomegaly (enlarged liver).
• Peripheral neuropathy, which can cause symptoms like heat, pain, itching, weakness, or excessive sweating.
• Eye problems, such as cholesterol deposits in the cornea, entropion (inward turning of the eyelid), drooping eyelids, muscle spasms in the eyes, and double vision.

Additionally, the risk of cardiovascular complications, such as heart attacks or strokes, increases significantly. More than 30% of individuals with this disorder experience premature heart attacks.

Tangier disease is usually detected through a blood test, which shows extremely low HDL cholesterol levels (below 5 mg/dl). Apolipoprotein A-1 (ApoA1) levels are also very low (<5 mg/dl).

The diagnosis can be confirmed with a genetic test that identifies a mutation in the ABCA1 gene.

There is currently no curative treatment for Tangier disease. However, the following recommendations can help manage symptoms:

• If the enlarged tonsils cause problems, they can be surgically removed.
• A low-fat diet may help reduce liver enlargement and lower the risk of atherosclerosis.
• Cholesteryl ester transfer protein (CETP) inhibitors, such as Dalcetrapib, Anacetrapib, or Evacetrapib, may help reduce cardiovascular and neurological complications, although their use in Tangier disease is still under investigation.