OMIM ID:
Tangier Disease
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This disorder of lipoprotein metabolism is associated in many cases with corneal infiltrates, cicatricial ectropion, poor lid closure, and exposure keratopathy. The corneal clouding alone generally cause little reduction of acuity but those with poor lid function and exposure keratopathy may have severe vision loss. There may be weakness in the periorbital and lid muscles. The corneal infiltration occurs late in life but is progressive with older individuals having the greatest visual impairment. The corneal infiltrates are described as a “dot-like haze”, more prominent centrally and located in the stroma. On electron microscopy, deposits in the conjunctiva are described as birefringent lipid particles located in pericytes and fibrocytes. Lipid deposition occurs throughout the body including the conjunctiva. Corneal hypesthesia has been reported.
In a series of 13 patients, ectropion and corneal scarring were reported in 3 and corneal infiltrates in 9. Four had orbicular muscle weakness. The latter together with corneal hypesthesia may be the earliest ocular signs of Tangier disease and should suggest the diagnosis even before the corneal clouding occurs.
Systemic Features
Patients with Tangier disease have significant enlargement of the liver, spleen and lymph nodes. The tonsils are also frequently enlarged and have a characteristic yellow-orange coloration. The enlargement of these organs is due to lipid infiltration. Plasma levels of cholesterol and HDL are characteristically slightly low while triglycerides are mildly elevated. Peripheral neuropathy and muscle atrophy can be debilitating. Severe coronary artery disease is common with onset sometime in the 5th decade.
Genetics
Inheritance
Tangier disease is an autosomal recessive disorder resulting from mutations in the ATP-binding cassette-1 gene ABCA1 (9p31.1) located in exon 22. Parental consanguinity is common.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.