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 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

Lecithin-cholesterol acyltransferase (LCAT) is involved in esterify of free cholesterol and in the cholesterol esters transport from peripheral tissues to the liver. Genetically dependent lack of enzyme activity leads to Fish Eye Disease and to familial LCAT deficiency. There are specific abnormalities of plasma lipids and lipid deposits in multiple tissues (familial LCAT deficiency) or in corneal only (Fish Eye Disease). Clinical features of familial LCAT deficiency include corneal opacities, anemia, and proteinuria. Renal failure is the most frequent complication, occurring in the fourth decade. Treatment of familial LCAT deficiency is based on infusions of plasma or whole blood and on kidney transplantation.
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PMID:[Clinical features of lecithin-cholesterol acyltransferase deficiency]. 774 88

Lecithin-cholesterol acyltransferase is responsible for the formation of most cholesteryl esters in plasma. Absence of this enzyme can result in a rare syndrome that includes diffuse corneal opacities, normocytic normochromic anemia, proteinuria, renal failure, and premature arteriosclerosis. The deficiency can be inherited in an autosomal recessive manner, or it can be acquired through liver disease. Diagnosis requires a high index of suspicion and documentation of impairment of enzyme mass or activity (or both). This article includes a case report of the first United States citizen known to have lecithin-cholesterol acyltransferase deficiency. The authors review the literature related to this disease.
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PMID:Lecithin-cholesterol acyltransferase deficiency: first report of case in a United States citizen. 802 2

We report a case of familial LCAT deficiency, diagnosed in a 35 year old women. The disease manifested itself by a presence of proteinuria, corneal opacities and haemolytic anaemia with target cells. Suspecion of familial LCAT deficiency was based on renal biopsy, which revealed characteristic serpiginous fibrillar deposits in electron microscopy. The diagnosis was confirmed by a marked decrease of estrified cholesterol, low HDL-cholesterol concentration, decrease of LCAT activity in serum, typical "stacked coins" picture of HDL lipoproteins in electron microscopy examination and positive familial history--diagnosis of LCAT deficiency in dialysed brother of patient.
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PMID:[Familial LCAT deficiency--clinical picture. Case report]. 1139 66

Familial deficiency of lecithin-cholesterol acyltransferase (LCAT) was described by Norum and Gjone in 1967. LCAT (EC 2.3.1.43) is a serum enzyme involved in reverse cholesterol transport. LCAT deficiency is associated with percentage increase of free cholesterol and decrease of esterified cholesterol, and disturbances in lipoprotein particles structure, because cholesterol esters form the lipoprotein core. Lipid disorders involve also other organs, such as kidneys, cornea and erythrocytes; with clinical manifestations of proteinuria, usually associated with renal insufficiency, corneal opacities and haemolytic anemia. Gene encoding LCAT is localized in region q 21-22 on chromosome 16. It consists of 6 exons, divided by 5 introns and spans 4.2 bp. Familial LCAT deficiency is an autosomal recessive disorder. In LCAT deficient patients several mutations in all 6 exons have been described. Clinical manifestations of familial LCAT deficiency are highly variable, although no or only low LCAT activity is present and this may suggests that expression of the disease is modulated by additional environmental factors and genes of minor importance.
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PMID:[Familial LCAT deficiency]. 1195 19

This review covers lipids, apolipoproteins, and receptors involved in the dyslipidemia of the nephrotic syndrome in humans and in rat or mouse models of the syndrome. It emphasizes research published during the last decade, though earlier work is cited. The focus is on the biosynthesis and catabolism of the plasma lipoprotein density classes and the role of receptors and enzymes in regulating lipoprotein metabolism in nephrosis. Although the factors responsible for the initiation of the hepatic and peripheral cellular responses to proteinuria and hypoalbuminemia remain elusive, recent work highlights the increased risk of atherosclerosis and the progression of renal disease associated with nephrotic dyslipidemia. Understanding of the role of the kidney in the catabolism of apolipoproteins entering the glomerular filtrate has been enhanced by the discovery of the receptor-mediated uptake of apolipoprotein A-I, the main apoprotein of HDL. The following aspects of lipid and lipoprotein metabolism in relation to nephrosis are discussed, with attention paid to differences between experimental nephrosis and the human nephrotic syndrome:(1) Albumin metabolism (2) Lipoprotein metabolism (3) Receptors (4) LCAT and CETP (5) Hepatic and Lipoprotein Lipase (6) Lipid metabolism (7) Lipiduria (8) Hypotheses and Questions (9) Summary.
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PMID:Lipoprotein metabolism in the nephrotic syndrome. 1213 20

Familial LCAT deficiency (FLD) is a rare genetic disorder associated with corneal opacities, anaemia and proteinuria with renal failure. Here we report detailed analyses on plasma lipids, lipoproteins, and the molecular defect in two siblings from a Polish family presenting classical symptoms of FLD and their family members with newly discovered Val309Met mutation in exon 6 of LCAT gene. Both patients displayed low total (2.19 and 2.94 mmol/l) and HDL-cholesterol concentrations (0.52 and 0.48 mmol/l), low percentage of cholesteryl esters (CE) (11.1 and 12%), and decreased apo AI and apo AII serum levels. Low LDL-cholesterol, apo B and Lp(a) levels, and increased oleate/linoleate ratios in CE could be of importance in the development of atherosclerosis in these patients with low HDL-cholesterol. LCAT activity was 10% of normal, alpha-LCAT activity was 0, and LCAT concentration was undetectable by immunoassay. Plasma CETP activity was at lower limits of normal. PCR and sequence analysis of DNA from the proband and affected brother revealed a novel G-->A mutation in exon 6 of LCAT gene, which resulted in an amino acid substitution of valine for methionine (Val309Met). The proband and affected brother were both homozygous carriers, while the mother, siblings and children of patients were heterozygous carriers of a newly discovered mutation. This is the first LCAT mutation described in the Slavic population.
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PMID:Familial lecithin-cholesterol acyltransferase deficiency: biochemical characteristics and molecular analysis of a new LCAT mutation in a Polish family. 1605 Dec 54

The esterification of free cholesterol (FC) in plasma, catalyzed by the enzyme lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), is a key process in lipoprotein metabolism. The resulting cholesteryl esters (CE) represent the main core lipids of low (LDL) and high density lipoproteins (HDL). Primary (familial) LCAT-deficiency (FLD) is a rare autosomal recessive genetic disease caused by the complete or near absence of LCAT activity. In fish-eye disease (FED), residual LCAT activity is still detectable. Here, we describe a 32-year-old patient with corneal opacity, very low LCAT activity, reduced amounts of CE (low HDL-cholesterol level), and elevated triglyceride (TG) values. The lipoprotein pattern was abnormal with regard to lipoprotein composition and concentration, but distinct lipoprotein classes were still present. Despite of typical features of glomerular proteinuria, creatinine clearance was normal. DNA sequencing and restiction fragment analyses revealed two separate mutations in the patient's LCAT gene: a previously described G to A transition in exon 4 converting Arg140 to His, inherited from his mother, and a novel G to C transversion in exon 2 converting Gly71 to Arg, inherited from his father, indicating that M.P. was a compound heterozygote. Determination of enzyme activities of recombinant LCAT proteins obtained upon transfection of COS-7 cells with plasmids containing G71R-LCAT or wild-type LCAT cDNA revealed very low alpha- and absence of beta-LCAT activity for the G71R mutant. The identification of the novel G71R LCAT mutation supports the proposed molecular model for the enzyme implying that the "lid" domain at residues 50-74 is involved in enzyme:substrate interaction. Our data are in line with the hypothesis that a key event in the etiology of FLD is the loss of distinct lipoprotein fractions.
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PMID:Compound heterozygosity (G71R/R140H) in the lecithin:cholesterol acyltransferase (LCAT) gene results in an intermediate phenotype between LCAT-deficiency and fish-eye disease. 1621 49

Familial lecithin-cholesterol acyltransferase deficiency is an uncommon autosomal recessive disorder from a heritable defect in esterification of plasma cholesterol. In 1968, the disease was described by Gjone and Norum in Norway. Our case was a 38-year-old woman. Her disease was manifested by presence of lower extremities edema, proteinuria, corneal opacities, increased plasma cholesterol, and hemolytic anemia. Suspicion of the disease was based on renal biopsy, which revealed mesangial expansion and capillary wall widening with clusters of foamy cells in the mesangium. Immunofluorescence study was nonspecific, but specific findings of electron microscopy showed deposition of lipid in the glomerular basement membrane and mesangium. This is the first report of lecithin-cholesterol acyltransferase deficiency in Iran.The diagnosis was confirmed by a low high-density lipoprotein cholesterol concentration, decreased activity of lecithin-cholesterol acyltransferase in plasma, and positive familial history of the disease.
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PMID:Familial lecithin-cholesterol acyltransferase deficiency. 1924 91

A 31-year-old man with no significant medical history presented with a 5-day history of progressive left upper quadrant abdominal pain. Physical examination revealed a tender guarded abdomen, no icterus, and bilateral corneal "arcus senilis"-like changes. Laboratory workup showed a mild normocytic, normochromic anemia; and target cells were seen in the peripheral blood smear. Serum was turbid; and the lipid profile showed elevated total cholesterol, low high-density lipoprotein cholesterol, and elevated triglycerides. Urinalysis revealed nephrotic range proteinuria with microhematuria. An abdominal computed tomographic scan demonstrated a homogeneously enlarged spleen. The patient was discharged after symptomatic treatment to be followed as an ambulatory patient. Several days later, he returned with severe left upper quadrant pain and was admitted to the surgical service for further evaluation. A splenectomy was performed for a suspected splenic lymphoma. Upon gross examination, spleen was moderately enlarged, weighing 780 g. Sectioning revealed a beefy red cut surface without gross lesions. Wright-Giemsa-stained touch imprints showed many sea-blue histiocytes. A renal biopsy was also performed, demonstrating focal segmental glomerular sclerosis and mesangial expansion with extramembranous and intramembranous deposition of lipids. In the absence of hematologic malignancy and in light of the abnormal lipid profile, a disorder of lipid metabolism was suspected. Histologic and ultrastructural findings in the kidney and spleen raised the likelihood of lecithin-cholesterol acyltransferase (LCAT) deficiency, which was confirmed by the markedly decreased serum LCAT activity and serum LCAT mass. We describe a case with the triad of splenomegaly with sea-blue histiocytes, nephropathy, and dyslipidemia in a patient with LCAT deficiency.
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PMID:Splenomegaly with sea-blue histiocytosis, dyslipidemia, and nephropathy in a patient with lecithin-cholesterol acyltransferase deficiency: a clinicopathologic correlation. 1959 52


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