Tangier disease E78.6

D. S. Fredrickson 1961. The first descriptor D. S. Fredrickson named the disease after the island of Tangier. Most of the patients documented to date come from this island. Some families originate from North Africa (El Khoury P et al. 2018), others have been described in Japan (Muratsu J et al. 2018).

Extremely rare autosomal recessive inherited disorder of lipoprotein metabolism with increased cholesterol storage in body cells.

So far, just over 100 people have been diagnosed.

The disease is caused by mutations of the ABCA 1 gene on chromosome 9q31 (several mutations with an identical phenotype have been described so far). ABCA 1 encodes a transport protein (ATP-binding cassette transporter 1; ABC1), a protein that regulates cholesterol "outward" transport. Due to this defect, only insufficient amounts of high-density lipoproteins (HDL) can be produced. Serum HDL deficiency leads to increased deposition of cholesterol and retinyl esters in peripheral nerves, dorsal nerve roots, liver, spleen, tonsils, lymph nodes, cornea, skin (reddish brown, glass pinhead-sized xanthomas) and intestinal mucosa.

Occurrence usually between the 4th and 6th decade of life.

Yellowish cholesterol deposits (flat xanthomas) in skin, in mucous membranes of mouth and throat. Especially the tonsils are affected by the discoloration and can be enlarged. Cholesterol storage is also seen in the rectal mucosa. Sometimes an anaemia exists. 50% of patients have peripheral neuropathy (Pasquale AD et al. 2019), which is known as

• syringomyelia-like neuropathy subtype
• recurrent motor-sensory mono-/polyneuropathy with onset in childhood or adolescence

become evident (Mercan M et al. 2018). Possible are hepato- and splenomegaly, premature arteriosclerosis (Muratsu J et al. 2018); somewhat less frequent are muscle weakness and male infertility (Stocchi L et al. 2018).

Abnormal profile of lipoproteins with isolated HDL deficiency (< 5 mg/dL), extremely low apolipoprotein A (< 5 mg/dL) and sole detection of pre-beta-1-HDL in two-dimensional plasma electrophoresis.

Other findings are: moderate hypertriglyceridemia, decreased LDL-cholesterol levels and occasionally decreased total plasma cholesterol. Liver function tests are usually normal. Possible findings are anemia, thrombocytopenia and mild signs of infection.

Causal therapy methods for the treatment of Tangier's disease are not available. A low-fat diet is generally recommended and genetic engineering therapy forms are conceivable in the future.

The prognosis is usually favourable and is mainly determined by the progression of peripheral neuropathy. TD patients with extremely low HDL cholesterol (<20 mg/dL) have an increased risk of coronary heart disease and cerebral insults in adulthood (Maranghi M et al. 2019).

Serum levels of total cholesterol, triglycerides, HDL cholesterol and apolipoprotein A-I are also meaningful. For cholesterol, values < 100 mg/dl are considered an indicator of Tangier's disease, while HDL cholesterol is usually completely absent.

1. El Khoury P et al (2018) Identification of the first Tangier disease patient in Lebanon carrying a new pathogenic variant in ABCA1. J Clin Lipidol 12:1374-1382.
2. Liang Z et al (2018) Tangier disease may cause early onset of atherosclerotic cerebral infarction: A case report. Medicine (Baltimore) 97:e12472.
3. Maranghi M et al (2019) A novel splicing mutation in the ABCA1 gene, causing Tangier disease and familial HDL deficiency in a large family. Biochem Biophys Res Commun 508:487-493.
4. Mercan M et al (2018) Peripheral neuropathy in Tangier disease: A literature review and assessment. J Peripheral Nerve Syst 23:88-98.
5. Muratsu J et al (2018) Accelerated Atherogenicity in Tangier Disease. J Atheroscler Thromb 25):1076-1085.
6. Pasquale AD et al. (2019) Nerve high-resolution ultrasonography in Tangier disease. Muscle Nerve 59:587-590.
7. Stocchi L et al. (2018) Can Tangier disease cause male infertility? A case report and an overview on genetic causes of male infertility and hormonal axis involved. Mol Genet Metab 123:43-49.