Tangier disease

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Classification according to ICD-10
E78.6 Lipoprotein
Deficiency Tangier Disease
E75.6 systematized lipid deposition disease
ICD-10 online (WHO version 2019)

The Tangier disease is a rare inherited disorder of fat metabolism . In this disease, the release of cholesterol from the cell is disturbed, which on the one hand leads to a reduced formation of high density lipoproteins and on the other hand to increased cholesterol storage, especially in cells of the reticulohistiocytic system . The main symptom are yellow-orange spots on enlarged tonsils . In addition, diseases of the nerves , enlargement of the abdominal organs and increased arteriosclerosis can occur. Overall, the prognosis is favorable, and causal therapy is currently not possible.

The term “Tangier disease” is used synonymously in the literature with “an-α-lipoproteinemia (anal phalipoproteinemia)”, “familial HDL deficiency” and “familial hypoalphalipoproteinemia”.

Historical aspects and dissemination

The Tangier disease has an autosomal - recessive inheritance.

The disease was named by Donald S. Fredrickson in 1961 after the island Tangier , which is isolated off the coast of Virginia , because the first two patients described came from there.

It is a rare disease . By 1978, 25 cases had been reported worldwide, by 1987 35 cases (including 21 with accompanying neurological symptoms) and by 2005 over 100 patients.

Cause and development of the disease

Tangier disease is inherited as an autosomal - recessive trait. The genetic defect underlying is localized on the long arm of chromosome 9 (9q31) and relates to the ABCA 1 - gene . The latter codes for a transport protein that is responsible for removing cholesterol from the cell.

The genetic defect disrupts the discharge of cholesterol from the cell, which together with apolipoprotein AI cannot contribute to the formation of high-density lipoprotein in the blood serum . This leads to an HDL deficiency with serum concentrations that are 100-200 times lower than that of normal persons, while cholesterol esters accumulate in the cell.

diagnosis

Scheme drawing of the key symptom. The right tonsil is typically changed, the left one is normal.

The main symptom is hypertrophic, yellow to orange colored almonds already in childhood . Fredrickson documented this change photographically in his first description. If the tonsils have been removed, reliable findings are small (1–2 mm diameter) spots in the mucous membrane of the anus . In addition to the typically changed tonsils, the levels of total cholesterol, triglycerides, HDL cholesterol and apolipoprotein AI in the blood are groundbreaking for the diagnosis . The α and pre-β bands in the lipoprotein electrophoresis are absent. The cholesterol level in the blood is below 100 mg / dl (mostly below 25 mg / dl) , the HDL cholesterol is missing, or the little that is still present in some cases is malstructured (like LDL and VLDL ) . The triglycerides , which can even be increased, are not affected . The apolipoprotein A-II is usually also reduced.

The clinical suspicion of Tangier disease can be confirmed by a human genetic examination. A nerve biopsy is usually not required to make a diagnosis.

Clinical picture

In addition to the already described enlargement and changes in the tonsils, muscle weakness and nerve symptoms , especially sensory disorders in the legs, as well as enlargement of the liver and spleen can occur. A massive enlargement of the pancreas has also been described in one individual case .

The absence of HDL cholesterol favors the development of arteriosclerosis . However, the course varies from person to person , so that coronary artery disease does not occur in some patients until they are older. Corneal opacity and changes in the blood count (e.g. haemolytic anemia , lack of blood platelets ) have also been described.

The neurological symptoms resulting from diseases of the peripheral nervous system can manifest themselves in three different forms. On the one hand as a distal sensorimotor neuropathy with sensory and movement disorders of the legs and arms, furthermore as a neuropathy affecting individual nerves (recurrent mononeuropathy) as well as a syndrome reminiscent of syringomyelia (pseudosyringomyelitic) with weakness of the facial muscles and the small muscles that begins in adulthood of the hand, missing or weak muscle reflexes , pain and temperature sensation and later also general sensory disorders in the trunk and extremities close to the trunk .

The nerve conduction velocity is normal in the first two forms mentioned. The extent to which these forms of disease differ not only in terms of tissue but also genetically has not yet been conclusively clarified, but is the subject of research.

pathology

In Tangier's disease, cholesterol esters are deposited in the macrophages of various tissues (e.g., peripheral and central nervous systems , spleen , lymph nodes , bone marrow , reticuloendothelial system , thymus , rectal lining, and skin ). These deposits are the cause of the clinically noticeable typical yellow-orange color of the tonsils . The fat-laden macrophages can be detected as foam cells in the infected tissues .

In the nerve biopsy of patients with the rare syringomyelia-like course, a sometimes pronounced reduction in myelinated and unmyelinated axons is found with evidence of vacuolization of Schwann cells and endoneural macrophages. In the (mono) neuropathic forms, only unspecific signs of de- and remyelination may be detectable.

Treatment and prognosis

A causal treatment of the disease has not yet been possible, but genetic engineering approaches are conceivable. A low-fat diet is generally recommended.

The prognosis is considered to be relatively favorable. In adulthood, however, there is an increased risk of developing vascular diseases, although a valid risk assessment is not possible due to the low number of known cases.

Individual evidence

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  10. ↑ a b Photograph of tonsils of a patient with Tangier Disease ; profiles.nlm.nih.gov ; last accessed on December 18, 2008
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  16. ↑ Züchner et al .: A novel nonsense mutation in the ABC1 gene causes a severe syringomyelia-like phenotype of Tangier disease . In: Brain , 2003, 126 (Pt 4), pp. 920-927, PMID 12615648
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  19. ↑ Pollock et al .: Peripheral neuropathy in Tangier disease . In: Brain , 1983, 106 (Pt 4), pp. 911-928, PMID 6317140
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This version was added to the list of articles worth reading on January 23, 2009 .