Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 16-year-old male (S.F.) and his 21-year-old sister (D.H.) from a large family of Italian and Swedish descent had virtually identical lipoprotein pattern and complete absence of LCAT activity. Both had typical corneal opacities and mild anemia with target cells. S.F., but not D.H., presented with proteinuria, which has increased over three years of follow-up. His kidney biopsy revealed lipid deposits in the glomerular basement membrane. Ten relatives in 4 generations had normal LCAT activity and/or lipoprotein pattern. The patients and their relatives had haptoglobin type 2. Factors that might influence the different clinical presentation in our patients (previous renal disease, diet, abnormal lipoproteins), prognosis, and treatment (diet, enzyme replacement, cholestyramine) are discussed.
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PMID:Familial LCAT deficiency. Report of two patients from a Canadian family of Italian and Swedish descent. 74 43

Recently, two cases of renal disease were observed in which there was an abnormal accumulation of lipids, "lipoprotein thrombi," in the glomerular capillary lumen. This disease has been designated as lipoprotein glomerulopathy. Four other cases have been diagnosed independently by renal histology in other clinical laboratories. All six patients showed proteinuria (1.6 to 10 g/d), normal lecithin-cholesterol acyltransferase (LCAT) activity, type III hyperlipoproteinemia-like lipoprotein profiles, and significantly (P less than 0.01) higher levels of plasma apolipoprotein (apo) E (greater than 10 mg/dL) compared with the control patients with hyperlipidemic nephrotic syndrome without lipoprotein thrombi and type IIb hyperlipoproteinemia without renal disease. Lipoprotein glomerulopathy is not familial type III hyperlipoproteinemia (dysbetalipoproteinemia), because apolipoprotein E3 is present. Apo E isoforms were all rare: five cases of E2/3 and one case of E4/4. These results suggest that excessive apo E is associated with apo E isoform and lipoprotein metabolic derangement in such a renal disease. Further studies are needed on the relationship between the apo E hyperlipoproteinemia and the formation of lipoprotein thrombi.
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PMID:Abnormal lipoprotein and apolipoprotein pattern in lipoprotein glomerulopathy. 195 34

Various pathological disorders are accompanied by the deposition of lipids into glomerular cells. To gain insight into these disorders, it is essential to know if glomerular cells possess lipoprotein receptors. We therefore characterized the activity of lipoprotein receptors in cultured epithelial cells of the human glomerulus. Podocytes were chosen as they are directly exposed to lipoproteins in pathological states like in glomerular proteinuria (such as, nephrotic syndrome). Isolated human glomeruli (purity greater than 95%) were incubated in buffered RPMI 1640 medium supplemented with 20% heat-inactivated fetal bovine serum at 37 degrees C and 5% CO2. Outgrowing cells were vimentin and keratin positive. Monolayer cultures of human glomerular epithelial cells upon incubation in lipoprotein deficient serum for 48 hours expressed a receptor-dependent uptake of lipoproteins. These cells showed about 10% of the maximal capacity for LDL uptake as compared to fibroblasts; however, the Km values for binding, internalization and degradation were similar in the cultures of glomerular epithelial cells and fibroblasts. The Km values for degradation of LDL, chylomicron remnants, beta-VLDL from cholesterol-fed rabbits and VLDL from familial LCAT-deficiency patients were 14.2, 4.9, 2.9, 4.5 micrograms protein/ml medium, respectively, for glomerular epithelial cells. The avid uptake of 125I-labeled apo E-containing lipoproteins was further substantiated by their poor displacement by a 25-fold excess of unlabeled LDL and their ability to down regulate the apo B,E receptor activity. LDL as well as beta-VLDL were able to suppress the incorporation of 14C acetate into sterols and to stimulate 3H-cholesterylester formation. These experiments show that cultured glomerular epithelial cells express lipoprotein receptor activity. Plasma concentrations of apo E-containing lipoproteins are increased in certain renal diseases (such as, nephrotic syndrome); these lipoproteins could be rapidly removed by glomerular epithelial cells and lead to lipid deposition in glomeruli.
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PMID:Receptor mediated uptake of apo B and apo E rich lipoproteins by human glomerular epithelial cells. 216 65

LCAT activity and mass were assayed simultaneously in 23 members of a new family case, revealing two homozygotes with a markedly low HDL--cholesterol level and ester cholesterol ratio. The LCAT mass in these patients was only 0.8 and 0.9 micrograms/ml, respectively (normal range 4.4-8.1) and their LCAT activity was 4 and 6 nM/ml/h 37 degrees C (normal range 60-120). Apolipoprotein (Apo) A-I and II levels were significantly low; however, apolipoprotein E tended to be high. In two-dimensional electrophoresis, apo A-I isoform visualized the increase of immature apo A-I; that is, A-I2. One subject showed the clinical characteristics of classic LCAT deficiency; however, the other, who was a vegetarian, showed corneal opacities and red cell deformity, but not proteinuria. This suggests that a low fat diet which decreases the level of atherogenic large LDL, may lead to a more favourable prognosis with a reduced risk for renal insufficiency. There were two different types of LCAT abnormality in this family series. Among the 10 examined paternal kindred of the proband who was one of two homozygotes, seven had a low LCAT mass but normal LCAT activity with the exception of one kindred who had a low mass and low activity. In contrast, among his seven maternal kindred examined, two had a low LCAT activity but normal mass.
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PMID:A new case of familial lecithin: cholesterol acyltransferase (LCAT) deficiency--paradoxical findings regarding LCAT mass and activity in 23 members of a family. 263 46

Familial LCAT deficiency is due to deficiency of plasma lecithin-cholesterol acyltransferase. The plasma is rich in free cholesterol and lecithin while cholesterol ester and lysolecithin levels are reduced. Analysis of the abnormal lipoproteins has helped our understanding of plasma lipid and lipoprotein metabolism in normals and in patients with liver disease. Proteinuria and anaemia are common and there is marked corneal lipid deposition. Eventually renal function deteriorates and dialysis and/or renal transplantation may be necessary. The human LCAT gene has been sequenced and been shown to be present on chromosomal segment 16q22-the region predicted on the basis of recombination studies as the site of the LCAT deficiency gene. The gene defect has been identified in some cases, but the mechanism remains unclear as the mutations were not in the region presumed to be the enzyme's active site. Only three cases of fish-eye disease have been described; all were elderly and had obvious corneal opacities. They had fasting hypertriglyceridaemia and increased VLDL. IDL and LDL were increased and were triglyceride rich. HDL, reduced by 90%, was mainly HDL3--with a high free and low ester cholesterol. LCAT activity in fish-eye plasma was normal but when measured in an exogenous substrate it was only 10-15% of normal. Fish-eye HDL is a substrate for purified LCAT, but fish-eye LCAT does not esterify free cholesterol of HDL (normal or fish-eye), although it esterifies free cholesterol of VLDL and LDL. It has been suggested that one type of LCAT activity acts on HDL (alpha-LCAT) and another on VLDL and LDL (beta-LCAT)--and that fish-eye disease is due to alpha-LCAT deficiency, and classical familial LCAT deficiency due to lack of both components.
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PMID:Familial LCAT deficiency and fish-eye disease. 314 86

Lecithin-cholesterol acyltransferase (LCAT) deficiency was first described in a Norwegian family as an inborn error of metabolism. Altogether, 35 patients in 18 families have been identified. The authors report the first German patient, who presented with the characteristic clinical features of corneal opacity, proteinuria, and mild anemia. Renal biopsy revealed foam cells and an increased mesangial matrix in the glomeruli. Confirmation of the clinical diagnosis of LCAT deficiency was obtained by plasma enzyme and lipid analyses. Functional LCAT activity was not detected in incubated plasma by chemical or radiochemical methods, although rocket immunoelectrophoresis indicated that the patient had about one-third of normal LCAT mass. In keeping with other reports of LCAT deficiency, apoE-rich discoidal particles were seen in the patient's high-density lipoprotein fraction by electron microscopic examination.
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PMID:Hereditary lecithin-cholesterol acyltransferase deficiency. Case report of a German patient. 366 2

Bilateral corneal opacities are the first clinical sign of a familial lecithin-cholesterol acyltransferase (LCAT) deficiency and can be found in early childhood. Familial LCAT deficiency includes the following typical clinical findings: corneal opacification, proteinuria, anemia, turbid or milky plasma, very low plasma HDL, very low plasma cholesterol esters and lysolecithin, hyperlipidemia, and very low or absent LCAT enzymatic activity. Several patients have had fundus findings including angioid streaks and papilledema. This disease is autosomal recessive and has been reported in a total of 19 patients previously. Progression of the disease has resulted in premature atherosclerosis, renal failure and transplantation, decreasing visual acuity and corneal transplantation.
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PMID:Corneal opacification and lecithin-cholesterol acyltransferase (LCAT) deficiency: a case report. 647 90

Two new cases of hereditary lecithin-cholesterol acyltransferase (LCAT) deficiency in a brother and sister born to consanguinous parents are reported. Both have corneal opacity, splenomegaly and mild hemolytic anemia. The brother, the older of the 2, also has significant proteinuria. The literature dealing with reported cases of hereditary LCAT deficiency and the clinical, pathological, diagnostic and management aspects of the disorder are reviewed.
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PMID:Hereditary lecithin-cholesterol acyltransferase deficiency. Report of 2 new cases and review of the literature. 683 94

Accumulation of glomerular foam cells were seen in a kidney biopsy of a 59-years old patient with persistent proteinuria and mild renal insufficiency. Further investigations revealed hypercholesterolemia, hypertriglyceridemia, normal activity of LCAT, absence of lipoprotein x. Foam cells which were shown by histochemical methods to be loaded with intracytoplasmic cholesterol were found in bone marrow. These findings strongly suggest cholesterol-ester-storage disease with glomerular involvement.
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PMID:[Mesangial lipidosis associated with cholesterol polycoria]. 714 95

Diminished autologous LCAT activity was found in patients with proteinuria. This was due to substrate limitation and albumin appeared the most likely limiting factors. It is suggested that low albumin can contribute to the hyperlipidaemia of nephrotic syndrome through its role on the LCAT reaction. Evidence of the ability of triglyceride to enhance homologous LCAT activity was also noted.
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PMID:The mechanism of hyperlipidaemia in nephrotic syndrome--role of low albumin and the LCAT reaction. 738 46


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