What Does Tangier Disease Do to the Body?

Tangier disease is a hereditary disorder, characterized by a significant reduction of high-density lipoprotein (HDL) in blood. HDL transports phospholipids and other types of fat from the body's tissues to the liver, where they are eliminated from the blood. HDL is usually referred to as "good cholesterol" because it reduces the risk of cardiovascular (heart and blood vessel) disease.

Due to their extraordinarily low HDL levels, people with Tangier illness have a slightly increased risk of cardiovascular disease. Although people with this condition are found all over the world, it was first identified on the island of Tangier, which is on the coast of Virginia.

Both genders are equally impacted by this rare autosomal recessive syndrome, which has been diagnosed in less than 100 families.

Tangier disease is caused by mutations in the ABCA1 gene. This gene gives instructions for producing a protein that allows cells to expel cholesterol and phospholipids. These components are involved in the creation of high-density lipoprotein (HDL), which carries phospholipids and other fats to the liver.

• The ABCA1 gene mutations block the release of phospholipids and cholesterol from cells.
• This results in the accumulation of these compounds within cells, causing certain body tissues to grow larger and the tonsils to attain a yellowish-orange hue.
• An accumulation of cholesterol can be harmful to cells as it results in impairing or even killing them.

Additionally, the inability to transport cholesterol and phospholipids out of cells results in very low HDL levels, which increases the risk of cardiovascular disease. These connected factors contribute to the signs and symptoms of Tangier disease.

The symptoms of Tangier disease vary from person to person, depending on where the fatty deposits crystallize.

Some symptoms of Tangier disease include:

• Atherosclerosis: A disorder marked by patchy atheromas or atherosclerotic plaques that form in the walls of medium and large arteries, which can cause arterial stenosis with decreased or restricted blood flow.
• Peripheral neuropathy: General term for any disorder of the peripheral nervous system. The four fundamental clinical traits that classify peripheral neuropathy are distribution, type (mainly demyelinating vs. largely axonal), duration, and course.
• Scarring: Formation of scar tissue.
• Corneal opacity: Reduction of corneal clarity.
• Hypertriglyceridemia: An abnormal increase in the level of triglycerides in the blood.
• Splenomegaly: An abnormally increased size of the spleen.
• Tonsillitis: Inflammation of the tonsils.
• Hepatomegaly: Abnormally increased size of the liver.
• Stomach pain
• Anemia
• Dry skin
• Muscle weakness in hands and legs
• Ectropion

The diagnosis of Tangier disease requires a high index of suspicion.

• In addition to clinical signs (which may appear earlier in the first decade or later in the second or third decade), the standard diagnostic tools for diagnosing patients remain to be blood values.
• Patients with Tangier disease frequently present with the following:
  • Low total plasma cholesterol (less than 150 mg/dL)
  • Low apolipoprotein A-I (less than 5)
  • Low high-density lipoprotein (HDL) (less than 5 mg/dL)
• Other blood findings include an average or higher triglyceride level, lower low-density lipoprotein (LDL) levels due to an elevation in LDL receptor expression, and thrombocytopenia.
• The most precise way to diagnose Tangier disease is through molecular gene sequencing of ABCA1. When genetic testing is not an option, tissue biopsies may be performed on the bone marrow, jejunum, liver, and rectum. All these organs would show large clusters of macrophages high in cholesterol.
• A few examples of tests that could be taken to evaluate multiple organ systems include:
  • Nerve conduction studies and electromyography to assess for peripheral neuropathy
  • Ophthalmologic evaluation to check for corneal opacities
  • Abdominal ultrasound to check for hepatosplenomegaly
  • Carotid duplex to check for carotid plaques
  • CT angiography to check for coronary atherosclerosis
• Family members of known diagnostic cases are regarded as high-risk individuals who should be tested to see if they are in the mutant gene carrier state. The prenatal diagnosis may also be provided. Checking a person's lipid profile (total cholesterol, HDL cholesterol, triglycerides, and estimated LDL cholesterol) and apo A-I concentration is a suitable way to follow up with at-risk individuals.

Currently, there is no known cure for Tangier's illness. Efforts can be made to improve high-density lipoprotein (HDL) through dietary changes, frequent cardiovascular activity, maintaining a healthy weight, quitting smoking, and replacing saturated fatty acids with monounsaturated fats. These treatments might help the symptoms, particularly with peripheral neuropathies.

Lipid-lowering medications including statins, niacin, and fibrates, which can be administered alone or in combination. However, there is no conclusive evidence to prove that drug therapy is beneficial in targeting low HDL cholesterol and improving low-density lipoprotein levels.

Treatment is given based on the symptoms; for example, a tonsillectomy is recommended for those with enlarged tonsils (which cause extreme discomfort, airway obstruction, or recurring infections).

For people with peripheral neuropathy, exercise, and temporary bracing (such as an ankle-foot orthosis) and in case of corneal opacities, corneal transplantation may be necessary. If the patient has splenomegaly, they should take certain precautions, such as avoiding high-impact sports or activities, to prevent splenic rupture.