A case of mesenteric panniculitis in a patient with Tangier disease

Mesenteric panniculitis is a rare disease caused by idiopathic inflammation of adipose tissue, most commonly affecting the mesentery of the small bowel. We present a unique case of mesenteric panniculitis in a patient with Tangier disease; a rare genetic disorder caused by mutations in the ABCA1 gene, leading to deficiency of high-density lipoprotein in the blood and accumulation of cholesterol esters within various tissues. The accumulation of cholesterol esters in body tissues in patients with Tangier disease may contribute to the pathogenesis of mesenteric panniculitis; although there is limited evidence to support this hypothesis due to the rarity of concurrent disease.     

Metabolism of high-density lipoprotein apolipoproteins in Tangier disease.

To define the metabolic defect in Tangier disease, we studied the kinetics of [125I]-high-density lipoprotein apolipoproteins (apolipoproteins A-I and A-II) in 11 normal subjects, two obligate heterozygotes, and two homozygotes. Mean synthesis of apolipoproteins A-1 and A-11 was 8.24 mg per kilogram per day in the normal group, 7.94 in heterozygotes and 3.66 in homozygotes. The mean plasma-residence time for both apolipoproteins was 5.21 days in the normal subjects, 3.41 days in heterozygotes, and 0.52 days in homozygotes. In normal subjects and heterozygotes the apolipoproteins were catabolized at similar rates, whereas in homozygotes apolipoprotein A-I was catabolized at a much greater fractional rate than apolipoprotein A-II. These findings indicate that the deficiency of these apolipoproteins in Tangier disease is largely due to rapid and altered catabolism.     

The heart in Tangier disease. Severe coronary atherosclerosis with near absence of high-density lipoprotein cholesterol.

Cardiac necropsy findings are described in a 72-year-old man with Tangier disease whose plasma total cholesterol levels averaged 70 mg/dL, low-density lipoprotein cholesterol level was 45 mg/dL, and high-density lipoprotein cholesterol level was 1.4 mg/dL, and who had coronary artery bypass grafting for severe atherosclerotic coronary artery disease. At necropsy, 24 of the 72 (33%) 5-mm segments of the 4 major (right, left main, left anterior descending, and left circumflex) native coronary arteries and 4 of the 27 (15%) 5-mm segments of the saphenous vein aortocoronary bypass conduits were narrowed by more than 75% in cross-sectional area by atherosclerotic plaques. The plaques were composed primarily (91% to 97%) of fibrous tissue. Oil red O staining, polarized light microscopy, and electron microscopy revealed cholesterol deposits in the plaques and in the walls of coronary arteries, saphenous vein grafts, and aorta. Such deposits also were found in foam cells of histiocytic origin, fibroblasts in all four cardiac valves, and in Schwann cells of cardiac nerves.     

Pathology of Tangier disease

Two cases of Tangier disease are described in children from families unrelated to each other. Necropsy in one case, the first to be reported in this condition, showed large collections of cholesterol-laden macrophages in tonsils, thymus, lymph nodes, and colon, and moderate numbers in pyelonephritic scars and ureter. As the storage cells may be scanty in marrow, jejunum, and liver, the rectum is suggested as the site of choice for biopsy.     

The pathology of cornea in Tangier disease (familial high density lipoprotein deficiency).

AIMS: To clarify the underlying causes of corneal opacification in Tangier disease. METHODS: Both corneas were removed at death from a 62 year old man with Tangier disease, and were examined by direct and transmission electron microscopy, histochemistry, biochemical analysis by thin-layer and gas-liquid chromatography after extraction, and by differential scanning calorimetry. RESULTS: Membranous inclusions in the stroma were seen on transmission electron microscopy. Direct analysis confirmed enrichment with phospholipids and cholesterol, with acyl patterns and proportions as ester broadly similar to those of normal cornea. Tangier cornea showed major thermotropic phase transitions in the range 28-37 degrees C, peak 30-33 degrees C, extending above profiles of normal clear cornea and without the complexity of those seen with cornea with heavy arcus involvement. CONCLUSIONS: Lipid accumulation underlies corneal opacification in Tangier disease. The excess material is mainly phospholipid and cholesterol esters. As at other sites which are below body core temperature, notably tonsil, accumulation may be enhanced by local impaired mobilisation of material as the phase transitions of the excess lipid present extend above ambient corneal temperatures.     

Transient dyslipidemia mimicking the plasma lipid profile of Tangier disease in a diabetic patient with gram negative sepsis

Tangier disease is a rare genetic disorder of lipid metabolism characterized by low concentrations of plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol with normal or elevated levels of triglycerides. In this case report we describe a patient with diabetes who experienced an episode of urosepsis with a plasma lipid profile resembling Tangier disease. Experimental evidence in the literature suggests that similar lipid changes may occur due to cytokines released during sepsis. Clinicians should be aware of these changes to avoid misdiagnosis of lipid disorders.     

Postprandial hypertriglyceridaemia in patients with Tangier disease

BACKGROUND: Tangier disease (TD) is the phenotypic expression of rare familial syndromes with mutations in the ABCA1 transporter. TD results in extremely low high density lipoprotein (HDL) cholesterol and reduced low density lipoprotein cholesterol, with normal or mildly increased fasting triglyceride (TG) concentrations. Although there is a close relation between HDL cholesterol values and atherogenesis, the risk of coronary artery disease is variable in TD. Raised fasting or postprandial TG values frequently accompany low HDL cholesterol and can add to the risk of a vascular event. AIMS: To investigate the postprandial TG response in TD. PATIENTS AND METHODS: Five patients (three homozygotes (HTD) and two heterozygotes (hTD)) from one family were studied. One was defined by DNA analysis as homozygous for a new mutation (C2033A) resulting in truncation of the ABCA1 protein. Their TG concentrations were measured before and four, six, and eight hours after a standardised fat load and compared with a control group. RESULTS: Two patients with HTD had high fasting TG concentrations. The third patient with HTD, the two with hTD, and the control group had TG concentrations within the reference range. The patients with HTD had increased postprandial peak TG values when compared with those with hTD and controls. CONCLUSION: Patients with HTD, with or without fasting hypertriglyceridaemia, may have an increased TG response to a fatty meal. The small number of patients does not allow definitive conclusions to be made. However, postprandial hypertriglyceridaemia could be a reason why some patients with TD develop premature atherosclerosis.     

Restriction enzyme analysis of the apolipoprotein A-I gene in fish eye disease and Tangier disease

Restriction enzyme analysis of the apolipoprotein A-I (apo A-I) gene was performed in two patients with fish eye disease and one with Tangier disease. Despite the marked deficiency of high density lipoprotein and concomitantly of apo A-I in these two conditions, no evidence was found for major deletions or insertions in the apo A-I gene.     

冠心病患者高密度脂蛋白亚组份的变化

本文应用聚丙烯酰胺凝胶电泳方法测定血清高密度脂蛋白(HDL)亚组份。发现冠心病患者HDL_2-胆固醇(HDL_2-C)含量及HDL_2-C/HDL_3-C比值明显低于正常人。测定其变化,为观察冠心病和研究HDL抗动粥机理提供了一个较好的参考指标。     

Salutary effects of hemodialysis on low-density lipoprotein proinflammatory and high-density lipoprotein anti-inflammatory properties in patient with end-stage renal disease

End-stage renal disease (ESRD) causes oxidative stress, inflammation, low-density lipoprotein (LDL) oxidation, high-density lipoprotein (HDL) deficiency and accelerated atherosclerosis. Uptake of oxidized LDL by macrophages results in foam cell and plaque formation. HDL mitigates atherosclerosis via reverse cholesterol transport and inhibition of LDL oxidation. ESRD heightens LDL inflammatory activity and suppresses HDL anti-inflammatory activity. The effect of hemodialysis on the LDL and HDL inflammatory properties is unknown. By removing the potential pro-oxidant/proinflammatory uremic toxins, dialysis may attenuate LDL inflammatory and HDL anti-inflammatory properties. Conversely, exposure to dialyzer membrane and tubing and influx of impurities from dialysate can intensify LDL and HDL inflammatory activities. This study examined the effect of hemodialysis on LDL and HDL inflammatory activities. Plasma samples were obtained from 12 normal control and 26 ESRD patients before and after hemodialysis with (16 patients) or without (10 patients) heparinization. HDL and LDL were isolated and tested for monocyte chemotactic activity in cultured endothelial cells. ESRD patients had increased LDL chemotactic activity, reduced HDL anti-inflammatory activity, paraoxonase and glutathione peroxidase levels, and elevated plasma IL-6 before dialysis. Hemodialysis partially improved LDL inflammatory and HDL anti-inflammatory activities and enhanced patients' HDL ability to suppress their LDL inflammatory activity. The salutary effect on LDL inflammatory activity was significantly greater in patients dialyzed with than those without heparin. ESRD heightens LDL inflammatory and impairs HDL anti-inflammatory activities. Hemodialysis partially improves LDL and HDL inflammatory activities. The salutary effects of hemodialysis are in part mediated by heparin, which is known to possess lipolytic and antioxidant properties.     

Tangier disease: one explanation of lipid storage.

Normal high-density lipoproteins are absent from plasma in Tangier disease, and the disorder is characterized by accumulation of cholesteryl esters in several tissues, particularly those of the reticuloendothelial system. Electron microscopy of the abnormal high-density lipoproteins in the plasma of three patients with Tangier diseases revealed large (68-nm), flattened, translucent particles in all cases. These particles were most abundant in the plasma of the splenectomized patient. Restriction of dietary fat eliminated or drastically reduced the numbers of these particles among the Tangier high-density lipoproteins. Thus abnormal products of chylomicron metabolism that appear to occur in plasma in this disorder may be targets for phagocytosis and may be at least one source of the cholesteryl esters that accumulate in reticuloendothelial tissues in Tangier disease.     

Tangier disease. A histological and ultrastructural study

A case of Tangier disease with results of histological and ultrastructural studies is reported. The clinical, biological and histological picture was typical, with enlarged liver and spleen, voluminous tonsils, low blood levels of alpha-lipoproteins and cholesterol and high blood levels of triglycerides. The histological study revealed widespread tissue storage of cholesterol esters in the Mononuclear Phagocyte System. Lipid deposits were located in foamy histiocytes by staining with lipid-specific stains. The ultrastructural study revealed intracytoplasmic vacuoles unbounded by membranes and often confluent. Unlike other previously described cases, this one had a rapid fatal outcome.     

Low-density lipoprotein apheresis is effective in reducing lipoprotein(a) levels and in improving symptoms in a patient with refractory angina secondary to accelerated coronary artery disease

Coronary artery disease remains a significant cause of morbidity and mortality in the Western world. High plasma Lp(a) concentrations are related to the risk of cardiovascular disease, but Lp(a) is rarely assayed and treated. We present the case of a 50-year-old gentleman with refractory angina, whose coronary disease continued to progress despite optimal medical and surgical therapy. We show that the aggressive reduction of Lp(a) successfully ameliorated the progression of coronary stenosis and provides effective and durable relief of symptoms.