What Is It?
Tangier disease (TD), also known as familial alpha-lipoprotein deficiency or hypoalphalipoproteinemia, is an autosomal recessive disorder with several systemic implications that can affect anesthetic management.1,2 The disorder was first diagnosed in a 5-year-old boy and his family who lived on Tangier Island in Virginia, hence the name. The syndrome is characterized by a severe reduction in the amount of high-density lipoprotein (HDL, the so-called “good cholesterol”), sterol deposition in tissue macrophages, and early-onset atherosclerosis.
The disease is caused by mutations in the adenosine triphosphate–binding cassette transporter ABCA1 gene, which is the gene responsible for the pathway that results in the release of cholesterol and phospholipids from cells.2-4 Apolipoprotein A1, a protein found in blood, normally combines with cholesterol and phospholipids to create HDL. Failure of the ABCA1 transporter allows cholesterol and phospholipids to build up intracellularly, causing tissue enlargement and impaired cellular function and, eventually, cell death. This transport inability causes very low HDL levels, increasing the risk for cardiovascular disease.5
Tangier disease has an autosomal recessive pattern of inheritance. Heterozygosity of allelic expression presents clinically as deficient HDL, whereas homozygosity presents as absent and near critically low HDL levels. Approximately 100 cases have been described worldwide, but this number may be an underestimation because the condition is often misdiagnosed as other familiar deficiencies, such as Niemann-Pick disease.
Mild hypertriglyceridemia is common in TD. In addition, 3 types of peripheral neuropathies are described.6 Type 1 is asymmetrical and often temporary or relapsing, and may involve ocular and facial nerves. Type 2 develops slowly, with symmetrical representation in the lower extremities. Type 3 displays syringomyelia-like symptoms, with loss of temperature and/or pain sensation. Initial atrophy and weakness in the face and upper extremities eventually spreads to the lower extremities.
Greatly enlarged tonsils that are orange or yellow in appearance are seen in more than 80% of cases. Premature atherosclerosis may occur, as well as splenomegaly, hepatomegaly, clouding of the cornea, and early-onset cardiovascular disease. Diarrhea is frequent and brown in color. Yellow mucosal spots are apparent on colonoscopy. HDL values are very low (<5 mg/dL).
Even though some drugs such as niacin or gemfibrozil can increase HDL, they have not been proven beneficial in TD. Current recommendations include diet modification, including maintaining a low-fat diet.
Thrombocytopenia is common in TD, and platelet and reticulocyte counts should be assessed. A hematology consult may be indicated. Avoidance of drugs, including herbal preparations, that affect coagulation is recommended. Succinylcholine and probably neuraxial anesthesia should be avoided in patients with extensive neuropathies, as response to pain and temperature testing may be absent. An exaggerated response to nondepolarizing muscle relaxants should be anticipated. Cardiac consultation may be obtained and liver function examined. Because of the hypertrophy of the tonsils, precise preoperative airway examination is essential. No single anesthetic technique has been shown to be superior.