Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Tangier Erkrankung

Die Tangier Erkrankung wird autosomal codominant vererbt. Die Mutationen des ABCA1-Gens führen zu einem Transportdefekt aus den cholesterinspeichernden Makrophagen. Laborchemisch finden sich deutlich erniedrigte HDL-Spiegel, die bei homzygotem Auftreten bis zum völligen fehlen führen können. Klinisch maniferstiert sich die Erkrankung mit gelben Tonsillen und einer Hepatosplenomegalie. Die Patienten zeigen zudem eine ausgeprägte Neigung zu kardiovaskulären Erkrankungen und eine periphere Neuropathie ist häufig.

Klinischer Befund

Die Klinik der Erkrankung ist durch die massive Ansammlung von Cholesterinestern in allen makrophagenhaltigen Geweben gekennzeichnet. So verfärben sich die sonst rötlichen Tonsillen orange bis gelblich. In Leber und Milz führen diese Ablagerungen zur Schwellung, Hepatosplenomegalie. In den Gefäßwänden sind sie für eine beschleunigte Arteriosklerose verantwortlich. In den Nervenscheiden sind sie die Ursache für eine periphere Neuropathie, die sowohl die sensiblen wie auch die motorischen Nerven betreffen kann.

Management

Die einzige effektive Möglichkeit die Erkrankung zu beeinflussen besteht über eine lipidarme Diät. Lipidsenker brachten keinen Erfolg.

Gliederung

Erbliche Fettstoffwechselerkrankungen
Dyslipidämie
Gestörte Regulatoren des Lipid- und Kohlenhydratstoffwechsels
Hepatischer CPT-Mangel Typ 1A
Meerblaue Histiozytenerkrankung
Statin-Intoleranz
Störung der Körperfettverteilung
Störungen der mRNA-Editiertfunktion
Tangier Erkrankung
ABCA1
Triglyceridspeicherkrankheit
Vermindete Cholesterinsenkung durch Statine

Referenzen:

1.

Young SG et al. (1999) The ABCs of cholesterol efflux.

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2.

Brooks-Wilson A et al. (1999) Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.

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3.

Bodzioch M et al. (1999) The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.

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4.

Rust S et al. (1999) Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1.

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5.

Remaley AT et al. (1999) Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred.

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6.

Rees A et al. (1984) Restriction enzyme analysis of the apolipoprotein A-I gene in fish eye disease and Tangier disease.

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7.

FREDRICKSON DS et al. (1964) THE INHERITANCE OF HIGH DENSITY LIPOPROTEIN DEFICIENCY (TANGIER DISEASE).

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8.

Ferrans VJ et al. (1975) The pathology of Tangier disease. A light and electron microscopic study.

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9.

Utermann G et al. (1975) Plasma lipoprotein abnormalities in a case of primary high-density lipoprotein (HDL) deficiency.

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10.

Schippling S et al. (2008) Severe Tangier disease with a novel ABCA1 gene mutation.

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11.

Assmann G et al. (1977) The lipoprotein abnormality in Tangier disease: quantitation of A apoproteins.

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12.

Assmann G et al. (1977) Isolation and characterization of an abnormal high density lipoprotein in Tangier Diesase.

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13.

Brook JG et al. (1977) Tangier disease (alpha-lipoprotein deficiency).

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14.

Assmann G et al. (1977) Characterization of high density lipoproteins in patients heterozygous for Tangier disease.

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15.

Schaefer EJ et al. (1978) Metabolism of high-density lipoprotein apolipoproteins in Tangier disease.

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16.

Schmitz G et al. (1985) Interaction of high density lipoproteins with cholesteryl ester-laden macrophages: biochemical and morphological characterization of cell surface receptor binding, endocytosis and resecretion of high density lipoproteins by macrophages.

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17.

Schmitz G et al. (1985) Tangier disease: a disorder of intracellular membrane traffic.

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18.

Law SW et al. (1985) Tangier disease. The complete mRNA sequence encoding for preproapo-A-I.

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19.

Makrides SC et al. (1988) Sequence and expression of Tangier apoA-I gene.

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20.

Pressly TA et al. (1987) Ocular complications of Tangier disease.

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21.

Frohlich J et al. (1987) Interaction of high density lipoprotein with adipocytes in a new patient with Tangier disease.

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22.

Pietrini V et al. (1985) Neuropathy in Tangier disease: A clinicopathologic study and a review of the literature.

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23.

Kocen RS et al. (1967) Familial alpha-lipoprotein deficiency (Tangier disease) with neurological abnormalities.

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24.

Engel WK et al. (1967) Neuropathy in Tangier disease. Alpha-Lipoprotein deficiency manifesting as familial recurrent neuropathy and intestinal lipid storage.

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25.

Lux SE et al. (1972) Studies on the protein defect in Tangier disease. Isolation and characterization of an abnormal high density lipoprotein.

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26.

Greten H et al. (1974) Lipoproteins and lipolytic plasma enzymes in a case of tangier disease.

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27.

Clifton-Bligh P et al. (1972) Tangier disease. Report of a case and studies of lipid metabolism.

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28.

Pollock M et al. (1983) Peripheral neuropathy in Tangier disease.

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29.

Schmitz G et al. (1983) Tangier disease: defective recombination of a specific Tangier apolipoprotein A-I isoform (pro-apo A-i) with high density lipoproteins.

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30.

Schaefer EJ et al. (1981) Metabolism of high density lipoprotein subfractions and constituents in Tangier disease following the infusion of high density lipoproteins.

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31.

Kay LL et al. (1982) Tangier disease: a structural defect in apolipoprotein A-I (apoA-I Tangier).

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32.

Suarez BK et al. (1982) Tangier disease: heterozygote detection and linkage analysis.

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33.

Zannis VI et al. (1982) Abnormal apoprotein A-I isoprotein composition in patients with Tangier disease.

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34.

Schaefer EJ et al. (1980) Coronary heart disease prevalence and other clinical features in familial high-density lipoprotein deficiency (Tangier disease).

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35.

Dyck PJ et al. () Adult-onset of Tangier disease: 1. Morphometric and pathologic studies suggesting delayed degradation of neutral lipids after fiber degeneration.

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36.

Cheung MC et al. (1993) Characterization of apolipoprotein A-I- and A-II-containing lipoproteins in a new case of high density lipoprotein deficiency resembling Tangier disease and their effects on intracellular cholesterol efflux.

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37.

Rust S et al. (1998) Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy.

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