Lecithin Acyltransferase Deficiency (Lecithin:Cholesterol Acyltransferase Deficiency)

An autosomal recessively inherited disorder caused by mutation of LECITHIN CHOLESTEROL ACYLTRANSFERASE that facilitates the esterification of lipoprotein cholesterol and subsequent removal from peripheral tissues to the liver. This defect results in low HDL-cholesterol level in blood and accumulation of free cholesterol in tissue leading to a triad of CORNEAL OPACITY, hemolytic anemia (ANEMIA, HEMOLYTIC), and PROTEINURIA.

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Networked: 310 relevant articles (10 outcomes, 31 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Lecithin Acyltransferase Deficiency (Lecithin:Cholesterol Acyltransferase Deficiency)
2.	Corneal Opacity
3.	Tangier Disease
4.	Arteriosclerosis
5.	Atherosclerosis

Experts

1.	Calabresi, Laura: 8 articles (11/2013 - 06/2004)
2.	Ng, Dominic S: 7 articles (12/2015 - 04/2002)
3.	Franceschini, Guido: 7 articles (11/2013 - 06/2004)
4.	Bujo, Hideaki: 5 articles (08/2014 - 02/2011)
5.	Connelly, Philip W: 5 articles (06/2012 - 04/2002)
6.	Kuroda, Masayuki: 4 articles (08/2014 - 02/2011)
7.	Remaley, Alan T: 4 articles (01/2013 - 06/2006)
8.	Boscutti, Giuliano: 4 articles (05/2012 - 09/2005)
9.	Saito, Yasushi: 3 articles (08/2014 - 02/2011)
10.	Aoyagi, Yasuyuki: 3 articles (08/2014 - 02/2011)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Lecithin 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." 06/11/2011 - "ApoA-I heterozygotes and subjects with partial or complete ABCA1 or LCAT deficiency had HDL with reduced antioxidant/anti-inflammatory properties and increased MDA levels. " 05/01/2007 - "Functional LCAT deficiency in human apolipoprotein A-I transgenic, SR-BI knockout mice." 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. " 05/01/1995 - "After a 1-minute pulse with labeled fibroblasts, efflux of [3H]UC into HDL-deficient plasmas decreased, compared with normal plasma, by 49% (apoA-I deficiency), 36% (TD), 21% (LCAT deficiency), and 28% (FED). "
2.	Phosphatidylcholine-Sterol O-Acyltransferase (Lecithin Cholesterol Acyltransferase)IBA 12/01/2013 - "Lecithin:cholesterol acyltransferase replacement therapy showed positive results in a patient with lecithin:cholesterol acyltransferase deficiency. " 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." 12/01/2011 - "We trace the 34-year history of a member of the first Japanese family in which lecithin-cholesterol acyltransferase (LCAT) deficiency was diagnosed. "
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.	CholesterolIBA 11/01/1987 - "Study of the components of reverse cholesterol transport in lecithin:cholesterol acyltransferase deficiency." 12/18/2015 - "We further showed complementary roles of LCAT deficiency and cellular cholesterol reduction in the SC-to-BAT adipogenesis. " 06/08/2012 - "Lecithin:cholesterol acyltransferase deficiency protects against cholesterol-induced hepatic endoplasmic reticulum stress in mice." 03/01/2009 - "Familial lecithin-cholesterol acyltransferase deficiency is an uncommon autosomal recessive disorder from a heritable defect in esterification of plasma cholesterol. " 05/01/2001 - "The LCAT activity in the proband was 5 nmol/ml/h and cholesterol esterification rate was 54.2 nmol/ml/h, consistent with LCAT deficiency. "
5.	HDL CholesterolIBA 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." 09/01/2014 - "Although rare, LCAT deficiency should be in the differential diagnosis of nephrotic syndrome in the setting of abnormally low HDL cholesterol levels." 06/01/2012 - "This paper reviews the genetic and biochemical features of LCAT deficiency, highlighting the absence of enhanced preclinical atherosclerosis in carriers, despite the remarkably low HDL cholesterol."
6.	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." 05/01/1997 - "Fish-eye disease: structural and in vivo metabolic abnormalities of high-density lipoproteins." 01/01/1987 - "In vitro normalization of cholesteryl ester content and particle size of fish eye disease high density lipoproteins." 01/01/1983 - "Serum high density lipoproteins (HDL) were isolated by preparative ultracentrifugation from two patients with fish eye disease (FED). "
7.	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."
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. " 09/20/1976 - "The increased content of triglycerides in LDL that may be found in liver disease, may not only be due to low H-TGL and LPL, but also LCAT deficiency." 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). " 01/01/1983 - "Fish-eye disease is a familial condition characterized by corneal opacities and dyslipoproteinaemia with, i.a., pronounced enrichment of plasma low density lipoprotein (LDL) with triglycerides. " 07/01/1993 - "We have identified the molecular defect in two siblings presenting with classical clinical and biochemical features of Fish Eye disease (FED), including corneal opacities, HDL cholesterol < 10 mg/dl, normal plasma cholesteryl esters, and elevated triglycerides. "
9.	Sterol O-AcyltransferaseIBA 09/01/2014 - "Lecitin cholesterol acyltransferase (LCAT) deficiency comprises a group of rare disorders related to HDL metabolism. " 11/01/2004 - "These abnormalities are, in part, due to acquired LCAT deficiency and upregulation of hepatic acyl-CoA:cholesterol acyltransferase (ACAT). " 12/01/1994 - "Familial plasma lecithine: cholesterol acyltransferase (LCAT) deficiency is a disease that is inherited as an autosomal recessing trait. " 01/01/1987 - "This finding confirms a deficiency of HDL lecithin:cholesterol acyltransferase activity (alpha-LCAT) in fish eye disease. " 01/01/1989 - "In the hypolipoproteinaemias, e.g., Tangier disease, generalised (alpha and beta) lecithin cholesterol acyltransferase (LCAT) deficiency, and alpha-LCAT deficiency (fish-eye disease), the absence or abnormality of HDL may impair clearance of endogenous and possibly exogenous stromal lipid. "
10.	very low density lipoprotein triglycerideIBA 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). " 02/01/1982 - "Fish eye disease (FED) is characterized by severe corneal opacities, causing impaired vision, and dyslipoproteinaemia: hypertriglyceridaemia, raised levels of very low density lipoproteins (VLDL), triglyceride enrichment of low density lipoproteins (LDL) and reduction of high density lipoproteins (HDL). "

Therapies and Procedures

1.	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. "
2.	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. "
3.	Kidney Transplantation 11/01/1997 - "Recurrence of lecithin cholesterol acyltransferase deficiency after kidney transplantation." 01/01/1994 - "Treatment of familial LCAT deficiency is based on infusions of plasma or whole blood and on kidney transplantation." 07/01/1993 - "Long-term follow-up of a patient with lecithin cholesterol acyltransferase deficiency syndrome after kidney transplantation." 07/01/1992 - "Successful renal transplantation in a patient with familial lecithin:cholesterol acyltransferase deficiency." 06/01/2013 - "The following corneal landmarks of systemic storage diseases and of the modern systemic therapy are presented: cornea verticillata in Fabry's disease, periodic infusion of alpha-galactosidase a; Kayser-Fleischer's ring in Wilson's disease, zinc, trienetin, low copper diet; multiple, punctiform crystals in cystinosis, cysteamine, Raptor RP 103(DR cysteamine) that reduces the cytotoxity in form of continous dissolving of cystine from lysosome, renal transplantation, haematopoietic stem cell transplantation; peripheral ring, but not true lipid arc, and moderate stromal haze in LCAT-deficiency, injection of recombinant enzyme or of encapsulated LCAT-secreting cells; diffuse stromal haze in mucopolysaccharidoses (MPS). "
4.	Total Parenteral Nutrition 01/01/2002 - "We have previously shown that infants receiving total parenteral nutrition have low apolipoprotein AI levels which are associated with high-density lipoprotein (HDL) class distributions as in lecithin:cholesterol acyltransferase deficiency. " 09/01/1984 - "An abnormal lipoprotein (LP), detected in plasma during total parenteral nutrition, has been shown to be similar to LPX observed in cholestasis and in familial lecithin-cholesterol-acyl-transferase (LCAT) deficiency. "
5.	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. " 10/01/2010 - "In summary, rLCAT treatment rapidly restored the normal lipoprotein phenotype in LCAT-KO mice and increased cholesterol efflux, suggesting the possibility of using rLCAT as an enzyme replacement therapy agent for LCAT deficiency."