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)

We present a six-year follow-up of a boy with a novel type of hypolipoproteinemia, with clinical and biochemical features distinct from classical hypoalphalipoproteinemias. There were abnormally low concentrations of total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) B, apo A-I, and apo A-II, and the phospholipids were decreased. The most striking abnormality was an extra fraction containing mainly phospholipids and apo A-I in the HDL3 subfraction. This fraction is reminiscent of concentric 20- to 50-nm-diameter lamellar phospholipid liposomes. Plasma lecithin:cholesterol acyltransferase activity was strongly decreased. We noted a persisting polyclonal hypergammaglobulinemia, hematological abnormalities (hemolytic anemia and thrombocytopenia), and a progressive splenomegaly. After the five-year follow-up, the patient had recurrent severe infections; moderate hematuria and proteinuria developed gradually. Treatment with corticosteroids and immunoglobulins improved thrombocytopenia and hypolipoproteinemia. These clinical and biochemical findings differ from those in the known primary and secondary hypo-alpha-lipoproteinemia syndromes. Although investigation of the relatives suggests a familial predisposition for hypo-alpha-lipoproteinemia, the subject's condition can be regarded as acquired.
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PMID:Acquired hypolipoproteinemia. 158 35

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

Lecithin:cholesterol acyltransferase (LCAT) and lysolecithin acyltransferase (LAT) are two activities carried out by the same plasma enzyme, but require different apoprotein activators. The LCAT reaction takes place primarily on high density lipoproteins (HDL) and is activated by serum albumin, whereas LAT takes place on low density lipoproteins (LDL) and is inhibited by albumin. In nephrotic syndrome (NS), the levels of serum albumin are reduced, whereas the LDL levels are increased, and therefore, the ratio of LAT/LCAT activities should be increased. To test this hypothesis, we estimated the lipid levels and the two enzyme activities in experimental NS induced in rats by the injection of anti-Fx1A antibody (passive Heymann nephritis). As found in other nephrotic conditions, the plasma lipid levels rose progressively as the proteinuria increased and the serum albumin concentration declined. In addition, the ratio of LAT/LCAT activities increased by about fourfold after nine days of induction of nephritis. The LCAT activity correlated positively and the LAT activity negatively with serum albumin levels. The esterified cholesterol correlated positively with LCAT activity in normal rats but negatively in nephrotic animals, indicating that most of the cholesteryl esters in NS may be non-LCAT derived. The free cholesterol/lecithin ratio, a known risk factor for atherosclerosis, increased significantly in nephrotic rats. Furthermore, since the increase in the LAT activity produces more disaturated lecithins, another putative risk factor, the cumulative risk of coronary heart disease may be increased in long-term NS.
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PMID:Plasma lipids and acyltransferase activities in experimental nephrotic syndrome. 277 94

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a well-defined inborn error of metabolism, where the enzymatic deficiency (LCAT) has been clarified and also the chromosomal defect (chromosome 16q22) is localized. The disease is to-day known all around the world and 50 patients from 26 families are known to-day. Corneal opacities have been found in all patients and appear early in life. The opacities have a characteristic appearance which makes it rather easy to get the correct diagnosis of this disease. Near the limbus, a pronounced opacity of annular shape resembling a marked arcus lipoides senilis occurs. The opacities are composed of numerous minute grayish dots and are localized to the parenchyma and evenly distributed in all layers of the stroma. In polarized light, crystals that may be cholesterol have been seen in both cornea and the fundus. Excess unesterified cholesterol and phospholipid has been found in cornea. The disease is also characterized by slight anemia and proteinuria and sometimes lipemic plasma, but patients without anemia and proteinuria have also been described. All lipoproteins are abnormal in familial LCAT deficiency. The individual lipoprotein fractions are all heterogeneous and characterized by a higher amount of free cholesterol than normal. Rapidly developing renal insufficiency in adult age often appears in this type of familial renal disease. Kidney transplantation may be necessary. LCAT has now been characterized as a glycoprotein with 416 aminoacids + hydrophobic leader sequence of 24 aminoacids and an apparent Mr of 63 kD. Plans exist to proceed with genomic cloning of the LCAT gene from normal DNA and from various patients.
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PMID:Familial lecithin: cholesterol acyltransferase (LCAT) deficiency. An updated review Spring 1988. 306 99

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

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

Familial lecithin:cholesterol acyltransferase deficiency is a rare autosomal recessive disorder associated with significant renal complications. A 16-year-old boy with the typical clinical and laboratory characteristics of this disease had a renal biopsy because of proteinuria and hematuria. The histologic findings were those of membranous glomerulonephritis with very few intracapillar foam cells. Ultrastructural study revealed numerous vacuolated deposits containing irregular profiles of electron-dense membrane-like material predominantly along with the subepithelial aspect of the glomerular basement membranes but also within the basement membranes, the subendothelial space, the mesangium, the capillary lumina, Bowman's capsule, and tubular basement membranes. The unusual aspects of this case are the relative paucity of intraglomerular foam cells and the predominantly subepithelial location of the lipid-like deposits.
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PMID:Unusual renal biopsy findings in a patient with familial lecithin:cholesterol acyltransferase deficiency. 707 12

A 38-year-old Asian man presented with acute pancreatitis, marked hypertriglyceridaemia and macroproteinuria, 20 years after the diagnosis of lecithin-cholesterol acyltransferase (LCAT) deficiency. After recovery, he exhibited macroproteinuria and chylomicronaemia despite treatment with a very-low-fat diet. Infusion of normal plasma significantly increased the proportion of cholesterol esters in the patient's plasma and significantly lowered chylomicron-triglyceride levels, but not proteinuria. We conclude that renal dysfunction may be a late manifestation of LCAT deficiency and that it may lead to severe chylomicronaemia and acute pancreatitis. Infusion of normal plasma corrects the dyslipidaemia in LCAT deficiency, but in the short term does not improve renal function.
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PMID:Lecithin-cholesterol acyltransferase deficiency presenting with acute pancreatitis: effect of infusion of normal plasma on triglyceride-rich lipoproteins. 762 81

We present findings in the ninth known Japanese family with lecithin:cholesterol acyltransferase (LCAT) deficiency. A 54-year-old man (proband) and his 58-year-old brother presented with corneal opacity. Both subjects showed a marked decrease in serum high density lipoprotein (HDL)-cholesterol and in the cholesteryl ester ratio. Although apo A-I and A-II were low, apo E tended to be high. Serum LCAT activity and mass were not detectable. Urinary examination showed microhematuria or proteinuria. Renal function was normal and no anemia was demonstrated, but blood smears showed poikilocytosis with target cells. The serum LCAT activity of the proband's three sons, obligate heterozygotes of LCAT deficiency, was about one-half the normal level, and HDL-cholesterol and apo A-I levels were low normal.
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PMID:Japanese family with a deficiency of lecithin:cholesterol acyltransferase (LCAT). 784 80


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