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Die Tangierkrankheit ist eine seltene autosomal recessive Fettstoffwechselkrankheit, welche durch das Fehlen normaler α-Lipoproteine (high density Lipoproteine) des Plasmas und zellulare Akkumulation von Cholesterinestern charakterisiert ist. Bis heute ist uber 25 Falle dieser Krankheit in der Literatur berichtet worden. Im Vordergrund der klinischen Symptomatik stehen Tonsillenhypertrophie, Splenomegalie und periphere Neuropathie. Die Cholesterinesterspeicherung findet man im wesentlichen in Makrophagen, Schwann'schen Zellen und intestinalen glatten Muskelzellen. Hypocholesterinamie (

Die Bestimmung von HDL-Cholesterin ermoglicht bei Patienten mit einer diskreten Hypercholesterinamie (240–300 mg/dl) die Differentialdiagnostik Hyperbetalipoproteinamie (=hohes atherogenes Risiko) oder Hyperalphalipoproteinamie (=geringes atherogenes Risiko). Andererseits dient die Analytik des HDL-Cholesterins der Pradiktion und Fruherkennung der koronaren Herzkrankheit, insbesondere in Verbindung mit bekannten Risikofaktoren (Hypertriglyzeridamie, Ubergewicht, Rauchen). Diese prognostische Bedeutung des HDL-Cholesterin resultiert aus der negativen Korrelation zwischen dem HDL-Cholesterinspiegel und der koronaren Herzkrankheit, die in epidemiologischen und klinischen Untersuchungen gefunden wurde.

Die High Density Lipoproteine sind ein heterogenes Gemisch von spharischen Makromolekulen, die sich durch die Partikelgrose (80–120 A), chemische Zusammensetzung (30–35% Apolipoprotein A–I, 10–15% Apolipoprotein A–II, 3–5% Apolipoprotein C, 25–30% Phospholipide, 15–20% Cholesterin/Cholesterinester, 3–5% Triglyzeride) und physikochemische Eigenschaften unterscheiden. Unter Routinebedingungen wird HDL nach selektiver Fallung Apolipoprotein B-haltiger Lipoproteine (very low density-Lipoproteine, low density Lipoproteine, Lipoprotein (a)) im Prazipitationsuberstand durch Bestimmung des Cholesterinanteils oder eines der Apolipoproteine der HDL quantifiziert. Ein wesentlicher Teil der HDL entsteht im Plasma aus diskoidalen Phospholipid-Apolipoprotein-Bilayern (Dicke: 46 A, Durchmesser: 190 A), die einerseits aus der Leber stammen und andererseits wahrend der Lipolyse der Chylomikronen gebildet werden. Die Rolle der diskoidalen HDL-Partikel als Cholesterinakzeptoren im Rahmen des zellularen Cholesterinstoffwechsels wird diskutiert.

Die von mir beschriebeneninfraclavicularen Infiltrationen, dieim Beginn der Erkrankung bei jugendlichen Erwachsenen mit reicher Infektionsmoglichkeit beobachtet werden, sind von groser theoretischer und praktischer Bedeutung fur den Entwicklungsgang der Tuberkulose. Bei entsprechender planmasiger Behandlung verlaufen sie meist gunstig; ohne diese kann aber auch ein unglucklicher Verlauf eintreten. Deshalb ist ihre rechtzeitigeFruhdiagnose und anschliesendeFruhbehandlung zu erstreben und mit allen Mitteln durchzufuhren.

Tangier disease is a rare autosomal recessive lipid transport disease characterized by the absence of the usual high density lipoproteins from plasma and cholesteryl ester storage in many organs. 25 cases of Tangier disease have been described so long. The predominant clinical symptoms include tonsilar hypertrophy, splenomegaly and peripheral neuropathy. The cholesteryl ester storage is limited to macrophages, Schwann's cells and intestinal smooth muscle cells. Hypocholest erolemia (less than 80mg/dl), hypertriglyceridemia (greater than 200 mg/dl), and the absence of high density lipoproteins in agarose electrophoresis are the major plasma abnormalities. The protein moiety of normal high density lipoprotein consists of apoprotein A-I and apoprotein A-II. In Tangier disease, serum concentrations of these apoproteins are reduced to less than 1% and 5-10%, respectively. Theories concerning the pathogenesis of Tangier disease are only incomplete and unproved up to now; however, a structural abnormality of apoprotein A-I causing an inability to bind to lipid or other proteins (apoprotein A-II) is consistent with several of the recent biochemical findings. The imbalance of cellular cholesterol metabolism caused by the absence of high density lipoproteins as well as the presumed role of these lipoproteins in cholesterol removal from cells are discussed in this article.

The determination of high density lipoprotein (HDL)-cholesterol in patients with mild hypercholesterolemia (240-300 mg/dl) allows one to distinguish between hyperbetalipoproteinemia (= high atherogenic risk) and hyperalphalipoproteinemia (= low atherogenic risk). In addition, analysis of HDL-cholesterol is of value in the prediction and early recognition of coronary heart disease, particularly in combination with known risk factors (hypertriglyceridemia, adipositas, smoking). This prognostic value of HDL-cholesterol is a result of its negative correlation to coronary heart disease which has been recognized in epidemiologic and clinical studies. The study of Tangier disease (analphalipoproteinemia) and tissue culture experiments will provide opportunities for the further elucidation of the role of HDL in atherogenesis.

High density lipoproteins are a heterogeneous mixture of spherical macromolecules which differ in size (80-120 A), chemical composition (apolipoprotein A-I: 30-35%; apolipoprotein A-II: 10-15%; apolipoprotein C: 3-5%; phospholipids 25-30%; cholesterol/cholesterol esters: 15-20%; triglycerides: 3-5%) and physico-chemical properties. They can be isolated through selective precipitation of apolipoprotein B-containing lipoproteins (very low density lipoproteins, low density lipoproteins, lipoprotein (a)) and, under routine conditions, quantitation can be performed by the determination of their cholesterol or apolipoprotein content. A considerable portion of high density lipoproteins originates in plasma from discoidal phospholipid-apolipoprotein bilayers (thickness: 46 A; diameter: 190 A). These bilayers are in part synthesized by the liver and in part derived from the surface of chylomicrons during lipolysis. The role of discoidal precursors of high density lipoproteins in cholesterol-uptake from peripheral cells will be discussed.

The influence of cigarette smoking on the concentration of HDL phosphatidyl choline was tested in 1,546 male and 778 female employees in Westfalia, and the results were compared with the influence of cigarette smoking on the concentration of HDL cholesterol. Three subgroups were established for comparison: non-smokers = persons who had never smoked; ex-smokers = persons who had in the past been smokers but were now non-smokers; and smokers = persons who at present smoked cigarettes. Neither male nor female smokers proved to have different HDL phosphatidyl choline values when compared to non-smokers or ex-smokers, whereas male and female smokers were found to have decreased HDL cholesterol values when compared to non-smokers (p less than 0.01) or ex-smokers (p less than 0.05). In female smokers a correlation was found between HDL phosphatidyl choline values and the number of cigarettes smoked every day (r = -0.12, p less than 0.05).

The intracellular catabolism of lipids and the blood cholesterol level are known to have an essential impact on the onset and progress of atherosclerosis. As lipoprotein receptors can influence the co-operation of macrophages, high density lipoproteins and enzymes of lipid metabolism, the contribution of these receptors to transport and intracellular processing of cholesterol are investigated by means of biochemical analysis and electron microscopy. Taking the effect of second messenger systems into consideration, a model for impaired lipoprotein receptor function affecting the cholesterol metabolism is developed.