Lecithin Cholesterol Acyltransferase Deficiency (Lecithin:Cholesterol Acyltransferase Deficiency)

An autosomal recessive disorder of lipoprotein metabolism caused by mutation of LECITHIN CHOLESTEROL ACYLTRANSFERASE gene. It is characterized by low HDL-cholesterol levels, and the triad of CORNEAL OPACITIES; HEMOLYTIC ANEMIA; and PROTEINURIA with renal failure.

Also Known As:

Lecithin:Cholesterol Acyltransferase Deficiency; Fish-Eye Disease; Dyslipoproteinemic Corneal Dystrophy; LCAT Deficiency; LCATA Deficiency; Norum Disease; alpha-LCAT Deficiency; alpha-Lecithin-Cholesterol Acyltransferase Deficiency; alpha-Lecithin:Cholesterol Acyltransferase Deficiency; Acyltransferase Deficiency, Lecithin:Cholesterol; Corneal Dystrophy, Dyslipoproteinemic; Deficiency, LCAT; Deficiency, alpha-LCAT; Fish Eye Disease; LCATA Deficiencies; alpha LCAT Deficiency

Networked: 410 relevant articles (12 outcomes, 46 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Lecithin Cholesterol Acyltransferase Deficiency (Lecithin:Cholesterol Acyltransferase Deficiency)
2.	Corneal Opacity
3.	Kidney Diseases (Kidney Disease)
4.	Tangier Disease
5.	Dyslipidemias (Dyslipidemia)

Experts

1.	Calabresi, Laura: 19 articles (01/2022 - 06/2004)
2.	Remaley, Alan T: 15 articles (01/2020 - 06/2006)
3.	Kuroda, Masayuki: 10 articles (08/2022 - 02/2011)
4.	Ossoli, Alice: 10 articles (01/2022 - 11/2013)
5.	Bujo, Hideaki: 10 articles (07/2021 - 02/2011)
6.	Freeman, Lita A: 10 articles (01/2020 - 01/2016)
7.	Franceschini, Guido: 10 articles (01/2017 - 06/2004)
8.	Ng, Dominic S: 9 articles (01/2018 - 04/2002)
9.	Simonelli, Sara: 7 articles (01/2021 - 05/2012)
10.	Boscutti, Giuliano: 6 articles (01/2022 - 09/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Lecithin Cholesterol Acyltransferase Deficiency:

1.	Apolipoprotein A-I (Apolipoprotein A1)IBA 07/01/1999 - "We conclude that the concomitant reduction in HDL and apoA-I concentrations and PON and PAF-AH activities is best explained by rapid clearance of the small HDL particles found in LCAT deficiency." 05/01/2007 - "Functional LCAT deficiency in human apolipoprotein A-I transgenic, SR-BI knockout mice." 11/01/2005 - "Point mutations in apolipoprotein A-I mimic the phenotype observed in patients with classical lecithin:cholesterol acyltransferase deficiency." 01/01/2002 - "The aim of this research is to co-express LCAT and it's natural activator apoA-I, with the recombinant adeno-associated virus vectors in the skeletal muscle cells, in order to pave a new way for gene therapy of the primary or secondary LCAT deficiency. " 03/22/1996 - "The biochemical changes in the 11.1 line, which is markedly deficient in plasma apoA-I, an activator for LCAT, are reminiscent of those in patients with partial LCAT deficiency. "
2.	Phosphatidylcholine-Sterol O-Acyltransferase (Lecithin Cholesterol Acyltransferase)IBA 12/04/1998 - "Two naturally occurring mutants of human lecithin-cholesterol acyltransferase (LCAT), T123I and N228K, were expressed in COS-1 and Chinese hamster ovary cells, overproduced, and purified to homogeneity in order to study the structural and functional defects that lead to the LCAT deficiency phenotypes of these mutations. " 01/01/1988 - "A study of the structure of the gene for lecithin: cholesterol acyltransferase in four unrelated individuals with familial lecithin: cholesterol acyltransferase deficiency." 02/01/1980 - "Study of erythrocytes in a hereditary hemolytic syndrome (HHS): comparison with erythrocytes in lecithin:cholesterol acyltransferase (LCAT) deficiency." 01/01/2023 - "A rare case of renal involvement in Lecithin-Cholesterol Acyltransferase (LCAT) deficiency: lessons for the clinical nephrologist." 11/01/2022 - "Familial lecithin: cholesterol acyltransferase (LCAT) deficiency (FLD) is a severe inherited disease without effective treatment. "
3.	Lipoproteins (Lipoprotein)IBA 11/01/2015 - "In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. " 01/01/2013 - "The measurement of plasma LCAT activity not only is important in the diagnosis of patients with genetic or acquired LCAT deficiency but is also valuable in calculating cardiovascular risk, as well as in research studies of lipoprotein metabolism. " 12/01/2001 - "In the present study, we describe the molecular defects in the LCAT gene and in lipoprotein metabolism of a 34-year-old patient presenting with features of classic familial LCAT deficiency. " 08/01/1984 - "Studies of lipoprotein metabolism in a patient with fish-eye disease." 11/01/1980 - "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. "
4.	LipidsIBA 06/01/2023 - "Among these, renal disease associated with LCAT deficiency is well characterized and lipid abnormalities detected in LCAT deficiency carriers mirror the ones observed in CKD patients, being present also in acquired LCAT deficiency. " 01/01/2023 - "Review of the ultrastructural kidney biopsy features demonstrated, in addition to membranous subepithelial and intramembranous usual-type electron-dense deposits, intramembranous osmiophilic lipid deposits similar to those in LCAT deficiency. " 01/01/2021 - "Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. " 11/03/2019 - "Lipid Profile Rather Than the LCAT Mutation Explains Renal Disease in Familial LCAT Deficiency." 01/01/2009 - "Lipid accumulation despite upregulation of the efflux (LXR, ABCA1, ABCG1) system in the aorta in CRF is largely due to upregulation of influx (SR-AI and LOX-1) pathway and LCAT deficiency."
5.	CholesterolIBA 11/01/1987 - "Study of the components of reverse cholesterol transport in lecithin:cholesterol acyltransferase deficiency." 08/01/2022 - "Given the clinical presentation, the complete lack of LCAT activity and cholesterol esterification rate, diagnosis of familial LCAT deficiency was made." 01/01/2020 - "In the individuals with LCAT deficiency, the plasma levels of the FA-esterified forms of cholesterol, 5,6αEC, 5,6βEC, CT, 7αHC, 7KC, 24SHC, 25HC, and 27HC, were significantly lower than those in the healthy volunteers. " 01/01/2018 - "Primed expression of PRDM16 and UCP in quiescent satellite cell caused by LCAT deficiency synergizes with cell cholesterol depletion to induce satellite cell-to-BAT transdifferentiation. " 11/01/2017 - "A patient from Romania with extraordinarily high total cholesterol levels and clinical and biochemical features consistent with familial lecithin-cholesterol acyltransferase deficiency is reported. "
6.	HDL CholesterolIBA 01/01/2020 - "Genetic LCAT deficiency is a rare metabolic disorder characterized by low-plasma HDL cholesterol levels. " 06/01/2012 - "Genetic LCAT deficiency is a rare metabolic disorder characterized by low HDL cholesterol levels. " 07/01/1997 - "The genetic and biochemical basis of fish-eye disease (FED) was investigated in a 63-year-old female proband with low plasma HDL cholesterol. " 10/14/1994 - "The signs in this case (cloudy cornea, marked decrease in serum HDL cholesterol concentration without premature arteriosclerosis) are typical of fish eye disease." 03/01/2019 - "However, they did not have any systemic associations with familial LCAT deficiency or Tangier disease, which are differential diagnoses for corneal clouding and low plasma high-density lipoprotein cholesterol. "
7.	HDL LipoproteinsIBA 03/01/1984 - "A study of the small spherical high density lipoproteins of patients afflicted with familial lecithin: cholesterol acyltransferase deficiency." 01/01/1983 - "Studies on high density lipoproteins in fish eye disease." 06/15/1977 - "Studies on the pre-alpha-lipoprotein in patients with familial lecithin: cholesterol acyltransferase deficiency." 12/01/2020 - "LCAT (lecithin cholesterol acyltransferase) deficiency results in severe low HDL (high-density lipoprotein). " 01/01/2001 - "Corneal opacifications in a low high density lipoprotein syndrome: suspicion of fish eye disease: a case report."
8.	Triglycerides (Triacylglycerol)IBA 04/01/1986 - "We have performed metabolic studies on a female patient with fish eye disease, a familial condition where plasma HDL levels are reduced by 90% and the concentration of plasma triglycerides is moderately increased. " 01/01/2022 - "Furthermore, plasma triglyceride-FA distribution was remarkably similar between carriers of LCAT deficiency and controls. " 05/01/1976 - "This method was applied to the study of 15 patients with hypertriglyceridemia and 8 patients with familial lecithin-cholesterol-acyltransferase deficiency of whom 6 also had a marked elevated plasma triglyceride concentration. " 03/01/2013 - "Mechanistic analyses indicated that LCAT deficiency was associated with enhanced intestinal absorption of dietary triglycerides (3.6±0.5mg/dl per minute for LCAT(-/-) vs. 2.0±0.7mg/dl per minute for C57BL/6 mice; P<.05), accelerated clearance of postprandial triglycerides and a reduced rate of hepatic very low density lipoprotein triglyceride secretion (9.8±1.1mg/dl per minute for LCAT(-/-) vs. 12.5±1.3mg/dl per minute for C57BL/6 mice, P<.05). " 11/03/2019 - "Renal disease is not only dependent on LCAT deficiency, and could be due to the presence of VLDL particles, which are rich in triglycerides, free cholesterol and LpX."
9.	Apolipoproteins E (ApoE)IBA 12/01/2009 - "Characterization of a new LCAT mutation causing familial LCAT deficiency (FLD) and the role of APOE as a modifier gene of the FLD phenotype." 08/01/1993 - "These results indicate that the elevated plasma apo E in LCAT deficiency was related not only to the lack of LCAT in the plasma, but also to fat intake. " 12/18/1989 - "Preparations with POPC:apoE molar ratios greater than 150:1 contained two distinct groups of complexes, also in the size range of discoidal apoE-containing HDL from patients with LCAT deficiency. " 12/18/1989 - "Gradient gel electrophoresis showed that these preparations contain discrete species both within (14-40 nm) and outside (10.8-14 nm) the size range of discoidal apoE-containing HDL reported in LCAT deficiency. " 08/01/1993 - "Effects of long-term, low-fat diet on plasma apo E in familial LCAT deficiency."
10.	Biomarkers (Surrogate Marker)IBA 01/01/2022 - "A systematic review of the natural history and biomarkers of primary lecithin:cholesterol acyltransferase deficiency." 01/01/2019 - "A proteomic approach to identify novel disease biomarkers in LCAT deficiency." 07/01/2011 - "Nevertheless, some monogenic forms, and especially those associated with LCAT deficiency, seem to break the rule, confirming once more the value of a proper diagnosis before drawing prognostic conclusions from a laboratory marker. " 01/01/2022 - "Here, we systematically review observational studies of FLD, FED, and heterozygous subjects, which summarize available evidence on the natural history and biomarkers of LCAT deficiency, in order to guide the development of novel therapeutics. " 01/01/2022 - "Furthermore, although biomarkers of LCAT deficiency have been identified, their suitability to monitor disease progression and therapeutic efficacy is unclear, as little data exist on the rate of progression of renal disease. "

Therapies and Procedures

1.	Therapeutics 08/01/2004 - "However, despite the cloning, study, and extensive expression of LCAT in mammalian cell lines, there is still no viable, clinical therapy for LCAT deficiency. " 01/01/2016 - "[Lecithin:Cholesterol Acyltransferase Deficiency, from genes to therapy]." 01/01/2016 - "The present therapy of LCAT deficiency is mainly aimed at correcting the dyslipidemia associated with the disease and at delaying evolution of chronic nephropathy. " 01/01/2020 - "Enzyme replacement therapy with recombinant human LCAT is the most clinically advanced therapy for atherosclerosis and familial LCAT deficiency (FLD), with Phase I and Phase 2A clinical trials recently completed. " 03/02/2015 - "The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome. "
2.	Enzyme Replacement Therapy 01/01/2019 - "LCAT Enzyme Replacement Therapy Reduces LpX and Improves Kidney Function in a Mouse Model of Familial LCAT Deficiency." 01/01/2016 - "LCAT deficiency represents a candidate disease for enzyme replacement therapy. " 10/01/2010 - "We examined the possibility of using LCAT an as enzyme replacement therapy agent by testing the infusion of human recombinant (r)LCAT into several mouse models of LCAT deficiency. " 07/01/2018 - "Recombinant human LCAT (rhLCAT) is now being developed as an enzyme replacement therapy for familial LCAT deficiency and as a possible treatment for acute coronary syndrome. " 01/01/2020 - "Enzyme replacement therapy with recombinant human LCAT is the most clinically advanced therapy for atherosclerosis and familial LCAT deficiency (FLD), with Phase I and Phase 2A clinical trials recently completed. "
3.	Fat-Restricted Diet (Diet, Fat Restricted) 08/01/1993 - "Effects of long-term, low-fat diet on plasma apo E in familial LCAT deficiency." 05/01/2013 - "Amelioration of circulating lipoprotein profile and proteinuria in a patient with LCAT deficiency due to a novel mutation (Cys74Tyr) in the lid region of LCAT under a fat-restricted diet and ARB treatment." 08/01/1993 - "To study the metabolic abnormalities in familial lecithin-cholesterol acyltransferase (LCAT) deficiency, the effects of a long-term, low-fat diet and LCAT replacement therapy on plasma lipids and apolipoproteins were investigated in a patient with LCAT deficiency. "
4.	Hormone Replacement Therapy (Therapy, Hormone Replacement) 06/01/1995 - "Studies conducted during the review period have also examined the mechanisms responsible for the low plasma concentrations of apolipoprotein A-I and apolipoprotein A-II in lecithin:cholesterol acyltransferase deficiency and the increased concentrations of HDL-apolipoprotein A-I caused by transdermal oestrogen hormone replacement therapy. "
5.	Penetrating Keratoplasty 01/01/2019 - "Penetrating keratoplasty may be necessary to provide better quality of vision in LCAT deficiency patients, specifically to enhance one's contrast sensitivity, despite relatively good Snellen visual acuity." 01/01/2019 - "The purpose of this study was to report a case of LCAT deficiency successfully treated with penetrating keratoplasty and longer-term follow-up with contact lens fitting. "