Introduction

Overview of Tangier disease

Tangier disease is a hereditary disorder where cholesterol esters deposit in the organs, specifically the reticuloendothelial systems, such as the liver, spleen, bone marrow, and lymph nodes. These organs can break down lipoproteins (cholesterol) and iron in the body and are also part of the immune system, where they remove harmful germs. Symptoms for Tangier disease include enlarged tonsils, spleen, and/or liver as well as peripheral neuropathy.

It was first found in siblings from Tangier Island in the United States in 1961, hence the name Tangier disease.¹ It is an autosomal recessive disorder caused by a mutation in the ATP-binding cassette transporter (ABCA-1) gene. ABCA-1 is a protein responsible for transporting phospholipids and free cholesterol, which are components of cholesterol, from inside the cells to the bloodstream.² When these components are in the bloodstream, they combine with lipoproteins to form cholesterol.

In autosomal recessive inheritance, both parents must carry the mutated gene for a child to be affected. Individuals with one copy of the mutated gene are carriers and typically do not exhibit symptoms.

Understanding cholesterol and triglycerides

Cholesterol and lipoproteins

Cholesterol is composed of lipids and proteins, forming structures known as lipoproteins. These include:

• Low-density lipoprotein (LDL): Often referred to as “bad” cholesterol because it can clog blood vessels (see Figure 1) when in excess levels in the blood and cause health issues such as stroke and heart attack³
• Very-low-density lipoprotein (VLDL): Is also considered “bad” cholesterol
• High-density lipoprotein (HDL): Is often known as “good” cholesterol because it can essentially unclog blood vessels by carrying “bad” cholesterol to the liver to be recycled or broken down to be excreted³

Triglycerides

Extra lipids in the body are converted to triglycerides and stored within fat cells.⁴ The triglycerides are broken down by the body when it needs to produce more energy. However, excess triglycerides can clog your blood vessels and cause issues such as stroke and heart attack. What differentiates them from cholesterol is that they do not have protein associated with them. 

Importance of laboratory findings

Laboratory testing is done on people who are suspected of having Tangier disease. Blood tests are the most common and easiest way to diagnose. Blood test includes a lipid profile, which tests for total cholesterol, HDL, LDL, and triglyceride levels.⁵ 

Lipid profile in Tangier disease

Cholesterol levels

The lipid profile in Tangier disease tends to present with low HDL at less than 5 milligrams/deciliter (mg/dl).⁶ This is because the cells within the body cannot release HDL into the bloodstream. Another marker for Tangier disease is a component of HDL called apolipoprotein (apoA-1), which can be lower than 10 mg/dl.⁶ 

Low HDL levels mean the total cholesterol level is reduced to less than 150 mg/dl. LDL cholesterol levels can sometimes be normal or 37% lower due to the liver taking up more LDL.⁶ On the other hand, triglyceride levels can be elevated or normal. 

VLDL-cholesterol can be elevated because the body increases VLDL production to compensate for the accumulation of cholesterol components or cholesterol esters within the cells. Below, you will find a table with reference ranges used by the NHS in a lipid profile. 

Table 1. Lipid profile results seen in Tangier disease with reference ranges.

* Commonly seen results in lipid profiles done for Tangier disease can vary from person to person

** Can include LDL and VLDL 

Your lipid profile can vary depending on your health and lifestyle. Talk to your doctor about cholesterol levels that are appropriate for you.

Additional blood test findings

Other tests can also confirm Tangier disease, such as:

• Lipoprotein electrophoresis: Can confirm low HDL by showing reduced or absent apoA-I bands.
• Liver function tests: May be abnormal due to hepatomegaly (enlarged liver)

What is happening in your body when you have Tangier disease?

People with Tangier disease are at a higher risk of atherosclerosis even though LDL levels are low. This is due to the accumulation of cholesterol esters in the blood vessels in tissues. Additionally, the macrophages, which are cells that belong to the immune system, take in excess cholesterol that collects within the tissues and turns into foam cells. These foam cells further clog blood vessels, leading to atherosclerosis.

Peripheral neuropathy is a condition that affects the nerves in the body. This condition occurs due to cholesterol accumulating around the nerves, disrupting the signals that are sent through the nerves.⁴ The accumulation of cholesterol can also cause swelling of organs such as the lymph nodes, spleen, and liver.   

A lipid panel is the main diagnostic test done when your GP or other medical professional suspects that you have Tangier disease. Furthermore, genetic tests are done to confirm the ABCA1 mutation. 

FAQs

Can Tangier disease be life-threatening?

Tangier disease is not life-threatening; however, early diagnosis is important to prevent the progression of the disease, which can lead to life-threatening issues such as stroke or heart attack. 

What is the treatment for Tangier disease?

There is no proven treatment plan for Tangier disease, although you may be recommended a healthy lifestyle that includes eating saturated fat-rich food and other healthy foods as well as exercising. It is also recommended not to smoke. Further research could include gene therapy, which is a target treatment that will try to fix the ABCA-1 mutation.

Do Tangier disease carriers show any signs or symptoms of the disease?

Tangier disease carriers tend to have no symptoms, but can have lower HDL levels. The HDL levels are usually not lower than someone with Tangier disease.

Summary

Tangier disease is a disease that results from cholesterol esters collecting within the cells due to a mutation in the ABCA-1 gene. The ABCA-1 gene codes for the protein responsible for releasing cholesterol esters from inside the cell to the outside. When in the bloodstream, these cholesterol esters combine with lipoproteins to form HDL. In Tangier disease, HDL levels and apolipoproteins tend to be low. LDL can be normal or lower, while triglycerides can be normal or elevated. VLDL tends to be elevated since there is not enough HDL cholesterol to clear VLDL. It is important to diagnose Tangier disease as early as possible, as the progression of this disease can lead to issues in the body, such as atherosclerosis, peripheral neuropathy, and swollen organs such as lymph nodes, the spleen, and the liver.