Tangier Disease

Tangier disease is an extremely rare inherited condition that causes you to have very low levels of HDL cholesterol in your blood. This type of cholesterol complex is known as “good cholesterol” because it helps get rid of the “bad” cholesterol complexes (LDL) that clog your arteries. Having a very low HDL level may raise your risk of heart disease. Plus, extra cholesterol can build up in different places in your body — like your tonsils, spleen or liver — making them too big.

This condition got its name from where it was discovered. In 1960, researchers identified the first case on Tangier Island, located in Chesapeake Bay. Other names for Tangier disease include:

• Hypoalphalipoproteinemia
• Familial alpha-lipoprotein deficiency
• High-density lipoprotein deficiency, type 1 (HDLDT1)
• High-density lipoprotein deficiency, Tangier type

Healthcare providers consider Tangier disease a type of lipoprotein metabolism disorder.

Symptoms of Tangier disease

Symptoms vary based on where in your body cholesterol builds up. In general, signs and symptoms of Tangier disease include:

• Enlarged tonsils, which may look bright orange or yellow-grey (this is a common early warning sign that typically appears by adolescence)
• Enlarged spleen and/or liver
• Problems with nerve function (peripheral neuropathy), which may involve muscle weakness or loss of sensation in your arms and hands
• Swollen lymph nodes in your neck, armpits and chest
• Clouding of your cornea (corneal opacity)
• High triglyceride levels
• Low platelet count

Tangier disease causes

A change to your ABCA1 gene causes Tangier disease. This gene tells your body how to make the ABCA1 protein, which helps cholesterol leave different cells in your body. This cholesterol should normally join up with special proteins called apolipoproteins to form HDL particles.

When you have Tangier disease, the ABCA1 gene doesn’t work as it should. This means cholesterol has trouble leaving cells. As a result:

• Cholesterol starts building up in your organs and tissues.
• Your body can’t make enough HDL particles, leading to low HDL cholesterol in your blood.

How is Tangier disease inherited?

Tangier disease follows an autosomal recessive pattern of inheritance. This means you need to inherit an abnormal copy of the ABCA1 gene from both of your biological parents to develop the disease.

If you inherit just one copy from one parent, you’re a carrier. You won’t develop the clinical symptoms, but you may have lower-than-normal HDL cholesterol levels. Because of this, experts sometimes consider Tangier disease to have an autosomal codominant inheritance pattern.

Complications of this condition

Tangier disease raises your risk of developing coronary artery disease earlier than expected — typically in your 50s or 60s. This may be due to the low level of HDL cholesterol in your blood. (Experts continue to study this link, though. That’s because existing medicines promoted to raise HDL so far haven’t been able to lower the risk of heart disease.)

HDL is often called the “good cholesterol” because it carries excess “bad cholesterol” (LDL) out of your blood. Without enough HDL to do this job, it may be easier for plaque to build up in your arteries (atherosclerosis).

How doctors diagnose this condition

Your healthcare provider can diagnose Tangier disease by doing a physical exam and blood tests. They look for typical signs like enlarged tonsils or spleen. Test results that suggest Tangier disease include:

• HDL cholesterol below 25 mg/dL (milligram per deciliter) — this is commonly below 5 mg/dL
• Apolipoprotein A-I (apoA-I) below 20 mg/dL
• Genetic testing that shows ABCA1 gene variants

You may need more tests after receiving a diagnosis. These help your provider learn more about how Tangier disease is affecting your body. Possible tests include:

• Ultrasound of your belly area to check your spleen and liver
• Nerve conduction study and electromyography to check nerve and muscle function
• Eye exams to see if there’s any clouding of your cornea
• Carotid ultrasound and CT angiogram to look for plaque in major arteries

How is Tangier disease treated?

Treatment for Tangier disease focuses on managing your symptoms and reducing your risk of plaque buildup in your arteries. Some people may need to have surgery to remove an affected area, like their tonsils or spleen. Braces or orthotics may help if you have problems with nerve function and movement. There’s no cure for Tangier disease, but gene therapy may help in the future.

To help protect your arteries, you may need to:

• Take medicine to manage blood pressure or cholesterol levels
• Avoid tobacco
• Eat heart-healthy foods
• Get some physical activity (as your provider recommends)

If you have an enlarged spleen, your provider will advise you on the types of exercises that are safe for you. You may need to avoid contact sports that could make your spleen rupture.

When should I see my healthcare provider?

You should see your healthcare provider regularly so they can respond quickly if your symptoms get worse. Follow the appointment schedule your provider gives you.

Your provider will do routine checkups of your:

• Nervous system
• Heart
• Eyes

What is the prognosis for Tangier disease?

Most people with Tangier disease have a good prognosis (outlook). But it depends on the features of the disease that affect you and their severity. Your healthcare provider can help you understand what to expect long term, including any impact on your life expectancy.

Tangier disease is a lifelong condition. Early diagnosis and continued checkups can help you manage this disease.

Since Tangier disease is genetic and you’re born with it, there’s no way to prevent it. If you’re planning on having children, you may wish to speak with a genetic counselor. They can help you understand the chances of your child having this condition.