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At least 883 records · Page 49Linked to original sources
PubMed1988

Lecithin:cholesterol acyltransferase deficiency.

Lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare familial disease inherited in an autosomal recessive pattern. It is characterized by a combination of plasma lipoprotein, corneal, erythrocyte and, in most patients, renal changes. The corneal changes consist of scattered stromal dots that are lipid deposits. Their composition is unique and suggests an intrinsic corneal metabolic defect. The corneal clouding is usually asymptomatic. Patients with the condition must be followed closely because renal failure may develop. We describe a patient with LCAT deficiency.

Adult↗
PubMed1987

Impaired intermediate-density lipoprotein triglyceride hydrolysis in familial lecithin:cholesterol acyltransferase (LCAT) deficiency.

A new lecithin:cholesterol acyltransferase (LCAT)-deficient family was found in Japan. In the proband, both LCAT activity and LCAT mass were deficient. The patient's parents, child, and sister, diagnosed as heterozygotes, had half-normal LCAT activity and LCAT mass. In the patient, an increase of intermediate-density lipoprotein (IDL, 1.006 less than d less than 1.019) fraction was observed. In postheparin plasma, both lipoprotein lipase and hepatic triglyceride lipase activities were low. Hydrolysis of [14C] triolein by human hepatic triglyceride lipase in patient IDL was decreased compared to that in IDL from normal postprandial serum. Preincubation of these IDL with normal plasma in the absence of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) increased the rate of hydrolysis, in the presence of DTNB, this increment was not observed. These results suggest that one cause of IDL increase in the LCAT-deficient patient might be the difficulty of hydrolysis of these lipoprotein particles by hepatic triglyceride lipase.

Adult↗
PubMed1985

Familial lecithin:cholesterol acyltransferase deficiency. Biochemistry of the cornea.

Opacification of the cornea from lipid accumulation is an early and characteristic feature of familial lecithin:cholesterol acyltransferase (LCAT) deficiency. Visual impairment in a female age 48 years led to keratoplasty and the first detailed analysis of cornea in this disorder. Multilaminar figures were present, and total lipid extracts were enriched with phospholipid and cholesterol; cholesteryl esters were reduced, and accounted for about 12% of the cholesterol. Linoleate C18:2 was the predominant residue in the cholesteryl ester fatty acid fraction, with a C18:1/18:2 ratio of 1:6.5. This ratio differs from that in normal cornea, and from that in plasma and in other tissue deposits in LCAT deficiency. Various disorders of the HDL/LCAT system in plasma can lead to corneal lipid accumulation and opacification. These disorders may share general defects of lipid clearance from the cornea, but this study of LCAT cornea indicates that the character of the accumulating lipid is significantly influenced by active local metabolism, irrespective of the defect in the HDL/LCAT system also present.

Chromatography, Gas↗
PubMed1984

Corneal opacification and lecithin-cholesterol acyltransferase (LCAT) deficiency: a case report.

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.

Adult↗
PubMed1982

Detection of heterozygotes for familial lecithin: cholesterol acyltransferase (LCAT) deficiency.

"Rocket" immunoelectrophoresis using specific anti-lecithin: cholesterol acyltransferase (LCAT) antiserum showed no immunoreactive protein in two patients with familial LCAT deficiency. Subnormal quantity of plasma LCAT was found in the maternal grandmother, the parents, and in two of four siblings of the patients (3.3-3.4 mg/l vs. 5.4 +/- 0.5 mg/l in 12 controls). The immunochemical quantitation of the enzyme correlated well (r = .93) with LCAT activity in an artificial substrate assay. These two methods allow detection of heterozygotes for LCAT deficiency.

Female↗
PubMed1983

Hereditary lecithin-cholesterol acyltransferase deficiency. Report of 2 new cases and review of the literature.

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.

Adult↗
PubMed1983

[Familial alpha lipoprotein deficiency. Tangier disease, familial hypoalphalipoproteinemia and familial deficiency of lecithin cholesterol acyltransferase deficiency].

The plasma lipoproteins are a group of macromolecules all of which transport lipids, including cholesterol, triglyceride and phospholipid, and all of which have one or more protein constituents, called apoproteins. It is becoming apparent that the apoproteins play an important role in lipoprotein metabolism. Recently the so called "alpha hypothesis" has been proposed, according to which a protective role for HDL in atherosclerosis has been postulated. Three "experiments of nature", characterized by deficiencies of HDL as genetic disorders, namely Tangier disease, familial hypoalphalipoproteinemia, familial lecithin: cholesterol acetyltransferase deficiency, support the "alpha hypothesis". The first italian cases with the genetic disorders are presented.

Adolescent↗
PubMed1982

Familial plasma lecithin: cholesterol acyltransferase deficiency. A new family with partial LCAT activity.

A 43-year-old woman and her 47-year-old brother were studied because of corneal opacity. They showed a marked decrease in plasma high density lipoproteins (HDL) and a decrease in the ester ratio of plasma total cholesterol. Discoidal particles were found in the HDL2 fraction (d 1.063-1.125). A marked heterogeneity of low density lipoproteins was disclosed in both patients by electron microscopy. Apoprotein analysis revealed an increase in apo E and a decrease in apo A-I and A-II in both patients. These abnormalities were similar to the data reported in other cases with hereditary lecithin : cholesterol acyltransferase (LCAT) deficiency. However, several interesting dissimilarities have been disclosed as compared with the previously reported cases. Neither patient had proteinuria, and their kidney functions were within the normal limits. The ester ratios of plasma cholesterol of both patients were the highest among the cases reported thus far. Their plasma LCAT activities were 14.4 and 15% of the normal mean values determined by Glomset-Wright's common-substrate method. The enzyme activities determined by Stokke-Norum's self-substrate method were 40.2 and 29% respectively. These results may indicate that this inherited disorder is not characterized by absence of plasma LCAT or presence of inhibitory factors in plasma, but by the presence of partially inactive LCAT in patients' plasma.

Adolescent↗
PubMed1982

Renal failure in familial lecithin: cholesterol acyltransferase deficiency.

Familial lecithin cholesterol acyltransferase (LCAT) deficiency is a rare inherited enzyme deficiency characterized by widespread disturbance of lipid metabolism and infiltration of many organs, including kidneys by lipids; usually it results in death from renal failure in the fourth or fifth decades. We have described a new family with LCAT deficiency and have studied three sisters with characteristic corneal opacities and no detectable plasma LCAT activity, together with eight obligate heterozygotes who have reduced LCAT activity but are phenotypically normal. All three sisters had the typical lipid abnormalities including large molecular weight particles in the low density lipoprotein (LDL) fraction of plasma previously described only in LCAT deficient patients with renal disease. However, only the youngest sister had proteinuria and renal failure. Renal biopsies from two of the sisters were infiltrated with lipid but the biopsy from the youngest contained electron dense deposits indistinguishable from those seen in immune complex disease. These findings cast doubt on the concept that large molecular weight LDL particles are the sole determinants of renal failure in LCAT deficiency.

Adult↗
PubMed1981

Erythrocyte alterations in praseodymium-induced lecithin:cholesterol acyltransferase (LCAT) deficiency in the rat: comparison with familial LCAT deficiency in man.

The intravenous administration of praseodymium nitrate (PrN) to rats was associated with parallel decreases in plasma lecithin: cholesterol acyltransferase (LCAT) activity and erythrocyte osmotic fragility at low doses (20 and 40 mg/kg) while higher doses (80 mg/kg) resulted in increases in both. Erythrocyte membranes from rats with PrN-induced LCAT deficiency exhibited small increases in cholesterol content, but not other alterations (e.g., in phospholipid profiles and sulfhydryl group latency) which characterize erythrocytes in familial LCAT deficiency in man. The administration of PrN caused a time- and dose-dependent accumulation of praseodymium in liver with hepatic levels being substantially greater in animals given the high (protective) as compared with the low (toxic) doses of PrN. Hepatic levels of glutathione were not altered by PrN administration, but hexobarbital sleeping time was markedly prolonged in animals receiving a toxic dose of PrN. It is suggested that dose-dependent alterations in the subcellular distribution of praseodymium may explain the paradoxical pathophysiological effects of high and low doses of PrN.

Animals↗
PubMed1981

Genetic control of lecithin-cholesterol acyltransferase (LCAT): measurement of LCAT mass in a large kindred with LCAT deficiency.

Lecithin-cholesterol acyltransferase (LCAT) mass was measured by radioimmunoassay in a large Sardinian kindred with LCAT deficiency. The frequency distribution of LCAT levels in the M-kindred demonstrated a trimodal distribution, one more corresponding to the normal controls and containing the normal relatives, a second mode completely separate from the controls and containing subjects with LCAT levels approximately one-half normal, and a third mode distinct from the other modes containing the two subjects with LCAT deficiency. Fifteen kindred members, including all six spouses, had enzyme levels of 4.92 +/- 0.49 microgram/ml (mean +/- SD), slightly lower but in the same range as controls (6.13 +/- 0.98; no. = 66). Twelve family members, including the two obligate heterozygotes, had enzyme levels of 2.68 +/- 0.32 microgram/ml, roughly one-half that of control levels. The LCAT-deficient subjects had enzyme levels of 0.30 and 0.37 microgram/ml, respectively. Segregation of the acyltransferase deficiency gene (LCATd) provided clear evidence of an autosomal recessive mode of inheritance of LCAT deficiency. Furthermore, the data strongly suggest that family members with half-normal enzyme levels are heterozygous carriers of the LCATd gene.

Adolescent↗
PubMed1980

Characterization of apolipoprotein E-rich high density lipoproteins in familial lecithin:cholesterol acyltransferase deficiency.

We have isolated and charachterized a subfraction of high density lipoproteins, rich in apolipoprotein E, from the plasma of patients afflicted with familial lecithin:cholesterol acyltransferase deficiency. Prepared by successive ultracentrifugal flotation, affinity chromatography on heparin-agarose, and affinity chromatography on conconavalin A-agarose, the subfraction contained disc-shaped lipoproteins that measured 14--40 nm in diameter and 4.4--4.5 nm in thickness. The major components were apolipoprotein E, phosphatidylcholine, and unesterified cholesterol, though other apolipoproteins and lipids were present in small amounts. A second subfraction of high density lipoproteins, isolated during the chromatography, contained apolipoproteins A-I and A-II, but no apolipoprotein E. This subfraction included disc-shaped lipoproteins, 13--24 nm in diameter, as well as small round particles, 5.7 nm in diameter. Both subfractions contained similar proportions of total protein relative to lipid, similar amounts of unesterified cholesterol relative to phosphatidylcholine, and a similar distribution of phosphatidylcholine fatty acid.

Adult↗
PubMed1980

Abnormalities in lipoproteins of d < 1.006 g/ml in familial lecithin:cholesterol acyltransferase deficiency.

Studies of different sized lipoproteins of d < 1.006 g/ml from patients with familial lecithin:cholesterol acyltransferase deficiency have yielded new evidence of abnormalities in this lipoprotein class. Lipoproteins of all sizes contain high amounts of unesterified cholesterol, low amounts of total protein, and particularly low amounts of apolipoproteins C-II and C-III. Lipoproteins 60 nm in diameter or larger include particles that show a notched appearance upon electron microscopy, and contain a) a high combined volume of phospholipid, unesterified cholesterol, and protein; b) high amounts of cholesteryl ester and apolipoproteins C-I and E, and c) two major tetramethylurea-insoluble proteins that can be separated by electrophoresis in the presence of sodium dodecylsulfate. In contrast, lipoproteins that are 40 nm in diameter or less appear to contain low amounts of cholesteryl ester, normal amounts of apolipoproteins C-I and E, and a single tetramethylurea-insoluble protein the size of that in control lipoproteins. Since these abnormalities occur in the lipoproteins of four different patients from four different families, they are probably effects of the enzyme deficiency. Most, however, appear to arise indirectly because in vitro experiments published earlier indicate that few are reversed by incubation in the presence of the enzyme and patient high density lipoproteins.

Adult↗
PubMed1995

[Lecithin: cholesterol acyltransferase (LCAT)--the genetic analysis of familial LCAT deficiency and fish eye disease].

Lecithin: cholesterol acyltransferase (LCAT) is the enzyme that catalyze the esterification of free cholesterol in plasma proteins. The functional abnormalities of LCAT are known to cause two diseases characterized by severe corneal opacity; familial LCAT deficiency that is accompanied with anemia and frequently, though not invariably, renal failure, and fish eye disease (FED) without any other severe symptoms. Notably, it has been shown that the clinical symptoms and biochemical features are highly variable in each patient with the diseases. Recent genetic studies on the cases of LCAT deficiency or FED revealed both diseases to be caused by respective mutations of the LCAT gene. These findings suggest the abnormal or defective LCAT by each gene mutation underlies the heterogeneity in the biochemical and, possibly, clinical characteristics observed in LCAT deficiency and FED.

Corneal Opacity↗
PubMed1995

Lecithin: cholesterol acyltransferase deficiency: identification of two defective alleles in fibroblast cDNA.

Previous mutations associated with lecithin:cholesterol acyltransferase (LCAT) deficiency have been identified using genomic DNA. To facilitate mutation analysis, we used cDNA from cultured fibroblasts which were shown to express LCAT mRNA. Using reverse-transcriptase PCR, LCAT cDNA was obtained from a 13-year-old boy with complete LCAT deficiency, characterized by low HDL-C (3 mg/dl), nondetectable initial cholesterol esterification rate, LCAT activity, and minimal LCAT mass (0.16 vs. 5-7.5 micrograms/ml). Sequencing of LCAT cDNA clones identified two mutations. A novel frameshift mutations caused by deletion of cytosine at the third nucleotide position of amino acid 168 (exon 5) predicts a disrupted protein catalytic site by converting Ser181-->Ala and creates a Pvu-II restriction site prior to premature truncation at amino acid 238. A C-->T transition results in a substitution of methionine for threonine at amino acid position 321 and creates an Nla-III restriction site on the maternal allele. Expression studies of mutant LCAT cDNA confirmed the virtual absence of LCAT activity in transfected COS-1 cells. The molecular defect in a young male with complete LCAT deficiency has been identified using fibroblast cDNA.

Adolescent↗
PubMed1995

In vitro expression of natural mutants of human lecithin:cholesterol acyltransferase.

Fish-eye disease (FED) and familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) are rare disorders of lipid metabolism linked to mutations in the LCAT gene. Eleven LCAT cDNA constructs associated with FED and FLD were prepared by site-directed mutagenesis and expressed in COS-6 cells. Analysis of total RNA from wild-type, FED, and FLD transfectants revealed that all contained LCAT-specific mRNA. Western blot analysis demonstrated that all LCAT transfectants synthesized LCAT. Mean LCAT secretion by FED transfectants was slightly lower than secretion by wild-type transfectants, whereas secretion by FLD transfectants was much lower. The specific activities of FED and FLD LCAT against model high density lipoproteins were 6% and 11%, respectively, of wild-type activity. The ratios of the LCAT activities against low density lipoproteins to those against model high density lipoproteins decreased in the order FED mutants > FLD mutants approximately wild type. FED and FLD LCAT mutants are different: the former are more active against low density lipoproteins, and the latter are less secretion-competent. The greater reactivity of FED LCAT against low density lipoproteins may explain the relative mildness of the clinical manifestations of FED compared to those of FLD.

Base Sequence↗
PubMed1994

[Clinical features of lecithin-cholesterol acyltransferase deficiency].

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.

Humans↗
PubMed1994

Evidence for impaired cellular cholesterol removal mediated by apo A-I containing lipoproteins in patients with familial lecithin: cholesterol acyltransferase deficiency.

We investigated the cholesterol reducing capacity of two species of lipoproteins containing apo A-I, one containing only apo A-I (LpA-I) and the other containing apo A-I and apo A-II (LpA-I/A-II), in 7 patients (4 homozygotes and 3 heterozygotes) with familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Interaction of normal LpA-I or LpA-I/A-II with macrophage foam cells induced a mass reduction in cholesterol from these cells and the cholesterol reducing capacity of LpA-I was greater than that of LpA-I/A-II. When foam cells were incubated with these lipoproteins from homozygotes or heterozygotes, the capacity of LpA-I and LpA-I/A-II particles to reduce cellular cholesterol was decreased by approx. 50% in the homozygotes but was increased by 25-50% in the heterozygotes. These results suggest that LpA-I and LpA-I/A-II isolated from homozygotes and from heterozygotes differ in their ability to accept cellular cholesterol. The former are poor and the latter good acceptors of intracellular cholesterol. We conclude that factors other than reverse cholesterol transport via apo A-I containing lipoproteins have to be considered to explain why homozygotes for LCAT deficiency are not at high risk for premature atherosclerosis.

Adult↗