Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 16-year-old male (S.F.) and his 21-year-old sister (D.H.) from a large family of Italian and Swedish descent had virtually identical lipoprotein pattern and complete absence of LCAT activity. Both had typical corneal opacities and mild anemia with target cells. S.F., but not D.H., presented with proteinuria, which has increased over three years of follow-up. His kidney biopsy revealed lipid deposits in the glomerular basement membrane. Ten relatives in 4 generations had normal LCAT activity and/or lipoprotein pattern. The patients and their relatives had haptoglobin type 2. Factors that might influence the different clinical presentation in our patients (previous renal disease, diet, abnormal lipoproteins), prognosis, and treatment (diet, enzyme replacement, cholestyramine) are discussed.
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PMID:Familial LCAT deficiency. Report of two patients from a Canadian family of Italian and Swedish descent. 74 43

Since 1967 a syndrome characterized by renal disease, normochromic anaemia and corneal opacities has been described in 7 members of 3 different Norweigan families. The patients have low levels of esterified cholesterol and lack LCAT (lecithin: cholesterol acyltransferase) activity in plasma. The genetic basis of the disorder seems to be the presence of a LCAT deficiency gene in double dose. This gene is probably the result of a single mutational event. Linkage studies revealed non-random assortment between LCTA deficiency and serum haptoglobin (Hp) types. After Hp subtyping a combined lod score of 3-41 at a recombination fraction of 0-00 was obtained. Association was revealed between the LCAT deficiency gene and the Hp-1S gene. We propose that the LCAT gene is situated close to the alpha-haptoglobin locus on chromosome no. 16.
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PMID:Genetics of LCAT (lecithin: cholesterol acyltransferase) deficiency. 80 50

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

The effect of the quality of dietary protein on the initiation of temporary anemia during vigorous physical training (sports anemia) was studied in dogs and rats. In the dog experiment, one group of dogs was fed a crude animal protein (AP) diet and the other a crude vegetable protein (VP) diet. After 6 weeks on the diets in a sedentary state (rest period), all the dogs were forced to run every day for two weeks (exercise period). The rat experiment was carried out using purified nutrient mixtures. Casein (C) was used as AP and gluten (G) as VP. Feeding was done for two weeks in two series with two diet groups of rats. One series was 15% protein feeding (15% C and 15% G) groups and the other 24% protein feeding (24% C and 24% G) groups. In each group, one group remained in a sedentary state (rest group), and the other ran vigorously on a treadmill every day for one week (exercise group). In a sedentary state, there was a slight tendency for the hemoglobin content or erythrocyte count to be reduced, even when the values remained within the normal range, in dogs and rats fed VP. On the other hand, after vigorous running, significant anemia (reduction of hemoglobin) appeared in the VP diet dogs and in all exercise rat groups except the 24% C group. It was confirmed that the anemia was caused by a reduction of erythrocyte resistance to hemolysis, which was closely related to changes in the lipid composition of blood (serum and especially erythrocytes). The change in lipid profile revealed by the experiments was a reduction of free cholesterol in blood associated with an increase of lysolecithin in dogs during the exercise period and in the rat exercise groups. It was suggested that repeated physical exercise increased the activity of LCAT (lecithin-cholesterol-acyltransferase) in the liver, spleen, etc., resulting in the above changes in lipid patterns in the blood. In dogs of AP and rats of 24% C, however, those changes in lipid pattern caused by exercise and sports anemia did not appear significantly. The different effects of the AP diet seemed to be due to the antagonistic effects of lysine, which was present in sufficient amounts in the diet. Thus the theoretical basis for our recommendation of a high amount of AP in the diet to prevent sports anemia was clarified by the present experiments.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of effects of vegetable protein diet and animal protein diet on the initiation of anemia during vigorous physical training (sports anemia) in dogs and rats. 361 20

Lecithin-cholesterol acyltransferase (LCAT) deficiency was first described in a Norwegian family as an inborn error of metabolism. Altogether, 35 patients in 18 families have been identified. The authors report the first German patient, who presented with the characteristic clinical features of corneal opacity, proteinuria, and mild anemia. Renal biopsy revealed foam cells and an increased mesangial matrix in the glomeruli. Confirmation of the clinical diagnosis of LCAT deficiency was obtained by plasma enzyme and lipid analyses. Functional LCAT activity was not detected in incubated plasma by chemical or radiochemical methods, although rocket immunoelectrophoresis indicated that the patient had about one-third of normal LCAT mass. In keeping with other reports of LCAT deficiency, apoE-rich discoidal particles were seen in the patient's high-density lipoprotein fraction by electron microscopic examination.
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PMID:Hereditary lecithin-cholesterol acyltransferase deficiency. Case report of a German patient. 366 2

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

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

In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to 3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys mutation we described previously. Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low-HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group (4.8%) than in the high-HDL-C group (1.6%). In addition, we identified 1 carrier of the intron 14G-->A mutation of cholesterol ester transfer protein (CETP) in the high-HDL-C group and subsequently demonstrated cosegregation of the mutant allele with elevated HDL-C levels in the proband's family. In conclusion, we have identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with the LPL Asn291Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns. This article also reports occurrence of a CETP mutation in subjects having non-Japanese roots.
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PMID:Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels. 955 65

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


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