Tangier Disease

A genetic disorder of cholesterol transport named for the secluded island of Tangier, off the coast of Virginia. Characteristically, patients present orange tonsils, very low levels of high-density lipoprotein (HDL), and enlarged liver and spleen.

High-Density Lipoprotein (HDL) Deficiency; Analphalipoproteinemia.

Although the molecular basis remains unknown, a mutation in the ABC1 (ATP-binding cassette) gene on chromosome 9q31 has been reported. ABC1 codes for a protein that helps rid cells of excess cholesterol. Autosomal codominant disorder. Heterozygotes do not have any clinical manifestations.

The primary problem appears to be a defect in cell signaling and in mobilization of cellular lipids, leading to intracellular cholesterol esters accumulation. This defect is compounded by a low plasma concentration of apolipoprotein A-I (an essential component of HDL) caused by a pathologically rapid catabolism. This results in a low level of HDL in plasma, making it unable to scavenge cholesterol from tissues. Tissues that accumulate excessive cholesterol include tonsils, liver, spleen, lymph nodes, thymus, intestines, and peripheral nerves. Histology reveals deposits of cholesterol esters outside of lysosomes in the cytoplasm.

Homozygotes have a marked deficiency of HDL cholesterol and apolipoprotein (apo) A-I levels (both <10 mg/dL), decreased low-density lipoprotein (LDL) cholesterol levels (about 40% of normal), and mild hypertriglyceridemia.

Large orange tonsils, splenomegaly, neuropathy, and rectal mucosal changes (orange-brown spots). Neuropathy may include demyelination (mononeuropathic or polyneuropathic) and axonal degeneration with a syringomyelic (dissociative) picture. Sensory loss may lead to global anesthesia but autonomic neuropathy has not been described. Unlike earlier beliefs, it is now known that the risk of atherosclerosis is increased in older patients. Mitral and pulmonary valve abnormalities have been reported. Loss of vision, incomplete eyelid closure. May have abnormal platelet function. The possibility of an association with cerebellar dysgenesis, cardiac defects and renal anomalies has been reported. Also, few case reports of annual pancreatic defect have been suggested. There is no specific treatment, although dietary fat restrictions are recommended.

Anemia and hemolysis, thrombocytopenia (prolonged bleeding time correctable with desmopressin acetate). Sleep apnea (airway obstruction). Liver function tests, electrolytes (malabsorption). ECG, echocardiogram, stress test/coronary angiography if ischemia suspected. Evaluate extent of neurological deficit, cranial nerve palsy (upper airway reflexes).

Rapid sequence induction is recommended if upper airway reflexes are lost. Complete airway obstruction is possible if tonsils are “kissing” (use nasopharyngeal airway to relieve). Meticulous positioning with adequate padding during surgery and recovery. Regional techniques are relatively contraindicated in the presence of neuropathy. Management depends upon systemic manifestations of the disease, such as ischemic heart disease. The presence of neuropathies or muscle weakness requires cautious use of muscle relaxants and patient positioning. Regional techniques should be avoided in the presence of neuropathy or platelet dysfunction. Care should be taken to protect the eyes.

Avoid succinylcholine if neuropathy is present (risk of hyperkalemia). Reduce the dosage of nondepolarizing muscle-relaxant drugs in patients with extensive neuropathy or muscle weakness. Use of muscle relaxants should be guided by neuromuscular monitoring. If sleep apnea is present, short-acting agents allow for rapid recovery (especially opioids).

Abetalipoproteinemia: An autosomal recessive inheritance disorder, most often observed in cosanguineous population. It is characterized by the absence of low-density lipoproteins and steatorrhea. Other clinical features include acanthocytosis, retinitis pigmentosa, ataxia, and mental retardation because of the reduced or absence of absorption of fat-based vitamins and other derivatives. Therefore, neurological complications are often delayed by the administration of large quantities of vitamins E and A.