Tangier disease is a rare autosomal recessive familial disorder of cholesterol metabolism, characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood, reduced total cholesterol, and increased triglyceride levels in serum. HDL transports cholesterol and certain fats called phospholipids from the body's tissues to the liver, where they are removed from the blood. HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. Tangier disease is clinically characterized by liver, spleen, lymph node and tonsil enlargement along with peripheral neuropathy in children and adolescents, and, occasionally, cardiovascular disease in adults.
The list of signs and symptoms mentioned in various sources for Tangier disease includes the following symptoms:
- Low HDL level
- Mild hypertriglyceridemia
- High fat levels in blood
- Enlarged tonsils
- Orange or yellow tonsils
- Premature atherosclerosis
- Enlarged spleen (splenomegaly)
- Enlarged liver (hepatomegaly)
- Cloudy cornea
- type 2 diabetes
- Early-onset cardiovascular disease
Mutations in the ABCA1 gene cause Tangier disease. This gene provides instructions for making a protein that releases cholesterol and phospholipids from cells. These substances are used to make HDL, which transports them to the liver.
Mutations in the ABCA1 gene prevent the release of cholesterol and phospholipids from cells. As a result, these substances accumulate within cells, causing certain body tissues to enlarge and the tonsils to acquire a yellowish-orange color. A buildup of cholesterol can be toxic to cells, leading to impaired cell function or cell death.
The diagnosis is based on evidence of an abnormal lipoprotein profile characterized by isolated HDL deficiency (<5 mg/dL) and extremely low apolipoprotein A-I (ApoA1) levels (< 5 mg/dL), with only pre beta-1 HDL found by bidimensional electrophoresis in the plasma. Moderate hypertriglyceridemia, decreased LDL cholesterol levels, and occasionally, decreased total plasma cholesterol are noted. Liver function tests are usually normal. Anemia, thrombocytopenia and mild inflammation may be observed. Skin or rectal mucosa biopsy reveals foam cells in affected tissues. Diagnosis is confirmed by genetic testing.
Prognosis is usually good and depends mainly on the progression of peripheral neuropathy. TD patients with extremely low HDL cholesterol (<20 mg/dL) present an increased risk of coronary artery disease in adulthood and should be offered regular cardiovascular and neurological monitoring.
The disease has no specific treatment. Tonsillectomy may be required in case of significant tonsillar enlargement. A low-fat diet helps in reducing liver enlargement and preventing atherosclerosis. LDL-lowering drugs are required in patients with overt signs of carotid atherosclerosis or cardiovascular disease. Therapies enhancing cellular cholesterol efflux by HDL (e.g. reconstituted HDL, CETP inhibitors) may reduce neuropathic and cardiovascular complications.