Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disorders of lipid metabolism, either hyperlipidemia or hypolipidemia, are associated with the formation of corneal opacities. Corneal arcus, the most commonly encountered peripheral corneal opacity, is frequently associated with abnormal serum lipid levels, but may occur without any predisposing factors. Reports also have linked corneal arcus with alcoholism, diabetes mellitus and atherosclerotic heart disease. Unilateral arcus is a rare entity that is associated with carotid artery disease or ocular hypotony. Diffuse corneal opacities associated with hypolipidemic disorders such as LCAT deficiency, fish eye disease and Tangier disease, may be the initial manifestation of these disorders and puts the ophthalmologist in a position to make an early diagnosis. Corneal arcus, along with a central corneal opacity, is seen in Schnyder's crystalline stromal distrophy. The association of the disorder with a dyslipidemia remains controversial. A review of lipid metabolism, corneal arcus and several disorders of lipid metabolism that affect the cornea are presented.
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PMID:The cornea and disorders of lipid metabolism. 192 41

Recombinant human interleukin-2 (rIL-2) is used to treat refractory cancers. During such treatment, patients develop severe hypocholesterolemia along with striking alterations in the concentration and composition of the circulating lipoproteins. The present study was undertaken to gather information about the pathogenesis of these abnormalities. Patients were studied before-, during- and after a 5-day course of high dose i.v. rIL-2. Whole plasma cholesterol was markedly reduced by rIL-2 administration (52%; P < 0.001), whereas the triglyceride concentration did not change. Thus, the lipoproteins became triglyceride enriched (P = 0.004). Low density lipoprotein cholesterol, apolipoprotein B (apoB), high density lipoprotein cholesterol, and apoA-I concentrations all decreased. Esterified cholesterol levels were markedly reduced. Total plasma apoE increased markedly, and two kinds of abnormal particles appeared: 1) beta-migrating, very low density lipoproteins; and 2) discoidal, apoE- and phospholipid-containing particles with abnormal density and electrophoretic mobility. The activities of two lipoprotein triglyceride hydrolases, lipoprotein lipase and hepatic lipase, fell significantly during treatment and returned promptly to pretreatment levels after rIL-2 was discontinued. Lecithin:cholesteryl acyltransferase (LCAT) activity also decreased significantly (64%) during treatment, but in contrast to the lipases, remained low for at least 5 days after the last dose of rIL-2 (P < 0.001). High dose i.v. rIL-2 induces severe dyslipidemia with deficiencies of both postheparin lipases and acute LCAT deficiency. Most, if not all, of the lipoprotein changes observed are explained by the LCAT deficiency that follows IL-2-induced hepatocellular injury and cholestasis.
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PMID:Acute dyslipoproteinemia induced by interleukin-2: lecithin:cholesteryl acyltransferase, lipoprotein lipase, and hepatic lipase deficiencies. 914 52

Splenomegaly with sea-blue histiocytes is not associated with dyslipidemia, except in severe cases of hypertriglyceridemia, Tangier disease, or lecithin cholesterol acyltransferase deficiency. We describe two kindreds in which the sea-blue histiocyte syndrome was associated with an apoE variant in the absence of severe dyslipidemia. Both patients presented with mild hypertriglyceridemia and splenomegaly. After splenectomy both patients developed severe hypertriglyceridemia. Pathological evaluation of the spleen revealed the presence of sea-blue histiocytes. A mutation of apoE was demonstrated, with a 3-bp deletion resulting in the loss of a leucine at position 149 in the receptor-binding region of the apoE molecule [apoE (delta149 Leu)]. Although both probands were unrelated, they were of French Canadian ancestry, suggesting the possibility of a founder effect. In summary, we describe two unrelated probands with primary sea-blue histiocytosis who had normal or mildly elevated serum triglyceride concentrations that markedly increased after splenectomy. In addition, we provide evidence linking the syndrome to an inherited dominant mutation in the apoE gene, a 3-bp deletion on the background of an apoE 3 allele that causes a derangement in lipid metabolism and leads to splenomegaly in the absence of severe hypertriglyceridemia.
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PMID:Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 Leu)]. 1109 79

Chronic renal failure (CRF) is associated with increased risk of arteriosclerotic cardiovascular disease and profound alteration of plasma lipid profile. Uremic dyslipidemia is marked by increased plasma concentration of ApoB-containing lipoproteins and impaired high-density lipoprotein (HDL)-mediated reverse cholesterol transport. These abnormalities are, in part, due to acquired LCAT deficiency and upregulation of hepatic acyl-CoA:cholesterol acyltransferase (ACAT). ACAT catalyzes intracellular esterification of cholesterol, thereby promoting hepatic production of ApoB-containing lipoproteins and constraining HDL-mediated cholesterol uptake in the peripheral tissues. In view of the above considerations, we tested the hypothesis that pharmacological inhibition of ACAT may ameliorate CRF-induced dyslipidemia. 5/6 Nephrectomized rats were treated with either ACAT inhibitor IC-976 (30 mg.kg(-1).day(-1)) or placebo for 6 wk. Sham-operated rats served as controls. Key cholesterol-regulating enzymes, plasma lipids, and creatinine clearance were measured. The untreated CRF rats exhibited increased plasma low-density lipoprotein (LDL) and very LDL (VLDL) cholesterol, unchanged plasma HDL cholesterol, elevated total cholesterol-to-HDL cholesterol ratio, reduced liver microsomal free cholesterol, and diminished creatinine clearance. This was accompanied by reduced plasma LCAT, increased hepatic ACAT-2 mRNA, ACAT-2 protein and ACAT activity, and unchanged hepatic HMG-CoA reductase and cholesterol 7alpha-hydroxylase. ACAT inhibitor raised plasma HDL cholesterol, lowered LDL and VLDL cholesterol, and normalized total cholesterol-to-HDL cholesterol ratio without changing total cholesterol concentration (hence, a shift from ApoB-containing lipoproteins to HDL). This was accompanied by normalizations of hepatic ACAT activity and plasma LCAT. In conclusion, inhibition of ACAT reversed LCAT deficiency and improved plasma HDL level in CRF rats. Future studies are needed to explore the efficacy of ACAT inhibition in humans with CRF.
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PMID:ACAT inhibition reverses LCAT deficiency and improves plasma HDL in chronic renal failure. 1528 Jan 62

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

A genetic mendelian autosomal recessive condition of deficiency of lecithin- cholesterol acyltransferase (LCAT) can produce two different diseases: one highly interesting nephrologic picture of complete enzymatic deficiency (lecithin:cholesterol acyltransferase deficiency; OMIM ID #245900; FLD), characterized by the association of dyslipidemia, corneal opacities, anemia and progressive nephropathy; and a partial form (fish eye disease; OMIM ID #136120; FED) with dyslipidemia and progressive corneal opacities only. The diagnosis of FLD falls first of all under the competence of nephrologists, because end-stage renal disease appears to be its most severe outcome. The diagnostic suspicion is based on clinical signs (corneal opacities, more severe anemia than expected for the degree of chronic renal failure, progressive proteinuric nephropathy) combined with histology obtained by kidney biopsy (glomerulopathy evolving toward sclerosis with distinctive lipid deposition). However, the final diagnosis, starting with a finding of extremely low levels of HDL-cholesterol, requires collaboration with lipidology Centers that can perform sophisticated investigations unavailable in common laboratories. To be heterozygous for a mutation of the LCAT gene is one of the monogenic conditions underlying primary hypoalphalipoproteinemia (OMIM ID #604091). This disease, which is characterized by levels of HDL-cholesterol below the 5th percentile of those of the examined population (<28 mg/dL for Italians), has heritability estimates between 40% and 60% and is considered to be a predisposing condition for coronary artery disease. 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. As in many other rare illnesses, trying to discover all the existing cases will contribute to allow studies broad enough to pave the way for further therapies, in this case also fostering the production by industries of the lacking enzyme by genetic engineering. Epidemiological studies, although done on selected populations such as hypoalphalipoproteinemia patients on dialysis and with the effective genetic tools of today, have been disappointing in elucidating the disease. Spreading the clinical knowledge of the disease and its diagnostic course among nephrologists seems to be the best choice, and this is the aim of our work.
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PMID:[LCAT deficiency: a nephrological diagnosis]. 2180 6

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease characterized by corneal opacities, normocytic anemia, dyslipidemia, and proteinuria progressing to chronic renal failure. In all FLD cases, a mutation has been found in the coding sequence of the LCAT gene. FLD is clinically distinguished from an acquired form of LCAT deficiency by the presence of corneal opacities. Here we describe a 36-year-old woman presenting with clinical, pathological, and laboratory data compatible with FLD. Her mother and elder sister had corneal opacities. However, genetic analysis revealed there were no mutations in the LCAT coding sequences and no alterations in LCAT mRNA expression. Furthermore, we were unable to find any underlying conditions that may lead to LCAT deficiency. The present case therefore demonstrates that LCAT deficiency may be caused by factors other than mutations in the coding sequence and we suggest that a translational or posttranslational mechanism may be involved.
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PMID:Lecithin-cholesterol acyltransferase (LCAT) deficiency without mutations in the coding sequence: a case report and literature review. 2195 68

We report a family with a rare genetic disorder arising out of mutation in the gene that encodes for the enzyme lecithin-cholesterol acyltransferase (LCAT). The proband presented with nephrotic syndrome, hemolytic anemia, cloudy cornea, and dyslipidemia. Kidney biopsy showed certain characteristic features to suggest LCAT deficiency, and the enzyme activity in the serum was undetectable. Mother and younger sister showed corneal opacity and dyslipidemia but no renal or hematological involvement. These two members had a milder manifestation of the disease called fish eye disease. This case is presented to emphasize the importance of taking family history and doing a good clinical examination in patients with nephrotic syndrome and carefully analyze the lipid fractions in these subset of patients.
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PMID:Co-existence of classic familial lecithin-cholesterol acyl transferase deficiency and fish eye disease in the same family. 2666 12

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive (AR) disease caused by mutation in the LCAT gene. LCAT enzyme esterifies cholesterol molecules in high-density lipoprotein(HDL) and low density-lipoprotein (LDL) particles. This enzyme deficiency is characterised by progressive corneal opacification, glomerulopathy, mild - moderate haemolytic anaemia and very low plasma levels of HDL. We here report a 34 year-old lady who presented with hypertension, nephrotic proteinuria, renal failure, corneal ring opacities, anemia and dyslipidemia. The diagnosis of familial LCAT deficiency was confirmed by clinical examination, characteristic dyslipidemia, undetectable LCAT levels in plasma and positive family history.
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PMID:Familial Lecithin Cholesterol Acyl Transferase Deficiency with Chronic Kidney Disease. 2776 13

LCAT synthesizes most of the plasma cholesteryl esters, and plays a major role in HDL metabolism. Mutations in the LCAT gene cause two syndromes, familial LCAT deficiency (FLD) and fish-eye disease (FED), both characterized by severe alterations in plasma lipoprotein profile. Renal disease is the major cause of morbidity and mortality in FLD cases, but an established therapy is not currently available. The present therapy of LCAT deficiency is mainly aimed at correcting the dyslipidemia associated with the disease and at delaying evolution of chronic nephropathy. LCAT deficiency represents a candidate disease for enzyme replacement therapy. In vitro and in vivo studies proved the efficacy of recombinant human LCAT (rhLCAT) in correcting dyslipidemia, and rhLCAT is presently under development.
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PMID:[Lecithin:Cholesterol Acyltransferase Deficiency, from genes to therapy]. 2796 11


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