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At a glance

Most severe form of familial deficiency or absence of high-density lipoprotein (HDL), apolipoprotein A-I and accumulation of cholesteryl esters in many tissues throughout the body. Characteristically, patients present yellow-orange tonsils, very low levels of HDL, and enlarged liver and spleen. It is named after the secluded island of Tangier, off the coast of Virginia.

Synonyms

High-Density Lipoprotein (HDL) Deficiency; Analphalipoproteinemia.

Genetic inheritance

Clinical autosomal recessive phenotype, the biochemical phenotype is inherited as an autosomal codominant trait. Twenty different mutations in the ATP-Binding Cassette transporter A1 (ABCA1) gene have been described.

Incidence

Very rare, about 100 patients have been diagnosed.

Pathophysiology

Tangier disease is caused by mutations in the ABCA1 gene, which encodes the membrane transporter ABCA1. This transporter plays a key role in the first step of reverse cholesterol transport, through which the efflux of free cholesterol from peripheral cells is transferred to lipid-poor apoA-I 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.

Diagnosis

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.

Clinical aspects

Large yellow-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. 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.

Precautions before anesthesia

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).

Anesthetic considerations

Rapid sequence induction is recommended if upper airway reflexes are lost. Complete airway obstruction is possible if “kissing” tonsils are present. Meticulous positioning with adequate padding during surgery and recovery. Regional techniques ...

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