Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0154251 (lipid disorder)
 795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tendon xanthoma are a hallmark of familial hypercholesterolemia and are among its earliest clinical manifestations. Achilles tendon size, advanced to a generally accepted marker, is virtually specific for the disease and easily accessible for measurement. Hypercholesterolemic patients with coronary heart disease have been reported to have larger diameters of the Achilles tendons than patients without coronary problems. Furthermore, Achilles tendon xanthomas have been shown to regress with treatment of the lipid disorder. Mainly radiological procedures were applied in the past to evaluate the diameters of the Achilles tendon but their use is limited by radiation protection. We have used real-time ultrasonography to evaluate the Achilles tendons of 38 patients with primary hypercholesterolemia and 32 normocholesterolemic controls. The anterior posterior diameter in the patients was 13.4 +/- 5.9 mm (range 6-20 mm) and 5.7 +/- 0.7 mm (range 5-8 mm) in the control group. In 8 patients with newly diagnosed and previously untreated hypercholesterolemia the thickness correlated highly with their age. The Achilles tendons in about half of the patients (n = 21) showed a homogeneous thickening, whereas the others revealed an inhomogeneous thickening indicating the presence of circumscribed xanthoma. Upon comparison of the ultrasonographic procedure with an established method (computed tomography) in 18 patients and 8 normal volunteers a highly significant correlation (r = 0.96) proved the validity of the sonography. We show that real time ultrasonography is a valid procedure to assess Achilles tendon diameters in patients with primary hypercholesterolemia. It can be applied frequently and may be useful to follow xanthoma regression during lipid lowering treatment.
 ...
PMID:Ultrasonography of achilles tendons in primary hypercholesterolemia. Comparison with computed tomography. 307 70

Hereditary factors play an important role in the etiology and progression of coronary heart disease (CHD), most probably by causing the appearance and the levels of its risk factors. To investigate if there is a correlation between familial hypercholesterolemia and HLA system antigens, 25 subjects of 7 families with familial hypercholesterolemia were compared with 14 normocholesterolemic related subjects. Compared to normocholesterolemic kindreds, the familial hypercholesterolemic subjects have a significant increased HLA-Bw35 antigen and a lack of HLA-A1. Therefore, the correlation found with some HLA system phenotypes improves our knowledge about familial hypercholesterolemia and aids in the identification of subjects affected with this disorder of lipid metabolism, which is one of the most important CHD risk factors.
 ...
PMID:Familial hypercholesterolemia and HLA antigens. 372 44

Although analysis of lipoprotein phenotypes is widely used to diagnose and classify the familial hyperlipidemias, an evaluation of this system as a method for genetic classification has hitherto not been published. The present study of 156 genetically defined survivors of myocardial infarction was therefore designed to examine the relationship between lipoprotein phenotypes and genetic lipid disorders. The lipoprotein phenotypes of each survivor was determined primarily by measurement of his plasma triglyceride and low density lipoprotein (LDL)-cholesterol concentrations; his genetic disorder was identified by analysis of whole plasma cholesterol and triglyceride levels in relatives. The mean levels of LDL-cholesterol discriminated statistically among the three monogenic lipid disorders; it was highest in survivors with familial hypercholesterolemia (261+/-61 mg/100 ml [mean +/-SD]); intermediate in those with familial combined hyperlipidemia (197+/-50); and lowest in those with familial hypertriglyceridemia (155+/-36) (P < 0.005 among the three groups). However, on an individual basis no lipoprotein pattern proved to be specific for any particular genetic lipid disorder; conversely, no genetic disorder was specified by a single lipoprotein pattern. This lack of correlation occurred for the following reasons: (a) individual LDL-cholesterol levels frequently overlapped between disorders; (b) in many instances a small quantitative change in the level of either LDL-cholesterol or whole plasma triglyceride caused qualitative differences in lipoprotein phenotypes, especially in individuals with familial combined hyperlipidemia, who showed variable expression (types IIa, IIb, IV, or V); (c) lipoprotein phenotypes failed to distinguish among monogenic, polygenic, and sporadic forms of hyperlipidemia; (d) clofibrate treatment of some survivors with genetic forms of hyperlipidemia caused their levels of triglyceride and LDL-cholesterol to fall below the 95th percentile, thus resulting in a normal phenotype; and (e) beta-migrating very low density lipoproteins (beta-VLDL), previously considered a specific marker for the type III hyperlipidemic disorder, was identified in several survivors with different lipoprotein characteristics and familial lipid distributions. These studies indicate that lipoprotein phenotypes are not qualitative markers in the genetic sense but instead are quantitative parameters which may vary among different individuals with the same genetic lipid disorder. It would therefore seem likely that a genetic classification of the individual hyperlipidemic patient with coronary heart disease made from a quantitative analysis of lipid levels in his relatives may provide a more meaningful approach than determination of lipoprotein phenotypes.
 ...
PMID:Hyperlipidemia in coronary heart disease. 3. Evaluation of lipoprotein phenotypes of 156 genetically defined survivors of myocardial infarction. 435 58

We have studied a large family of 95 members with a defect in the metabolism of cholesterol, which is transmitted through three generations. The following characteristics of the family support the classification of the disorder as familial hypercholesterolemia : hypercholesterolemia, increased levels of phospholipids an beta-lipoproteins, normal values of triglycerides, pre-beta-lipoproteins and blood sugar, xanthomas, xanthelasmas, corneal arcus and early appearance of ischemic heart disease. Segregation analyses of the hypercholesterolemia and the findings of a bimodal distribution of total plasma cholesterol in the family suggest a monogenic autosomal dominant mechanism of transmission of this lipid disorder.
 ...
PMID:Familial hypercholesterolemia: mechanism of inheritance. 743 91

Familial combined hyperlipidemia (FCHL) is the most common genetic lipid disorder among young survivors of myocardial infarction. Elevations of plasma total and low-density lipoprotein (LDL) cholesterol and the prevalence of small, dense LDL particles are both involved in the high coronary risk of FCHL patients. We investigated the ability of pravastatin to favorably correct plasma lipid and lipoprotein levels and LDL structure in FCHL patients. Twelve patients with FCHL, documented by studies of first-degree relatives, received pravastatin (40 mg/d) for 12 weeks. Pravastatin significantly lowered plasma total and LDL cholesterol levels by 21% and 32%, respectively. Triglyceride levels did not change, and apolipoprotein B (apoB) concentrations decreased by 9% (P = NS). High-density lipoprotein (HDL) cholesterol increased by 6% because of a significant 73% rise of HDL2 cholesterol. LDL were smaller (diameter, 24.5 +/- 0.5 nm), less buoyant, and apoB-rich (cholesteryl ester-apoB ratio, 1.64 +/- 0.46) in the selected patients compared with patients with familial hypercholesterolemia or healthy control subjects. LDL became even smaller (23.8 +/- 0.6 nm) and richer in apoB (cholesteryl ester-apoB ratio, 1.27 +/- 0.52) after pravastatin treatment. Although pravastatin favorably altered plasma lipid and lipoprotein levels in FCHL patients, the abnormal LDL particle distribution and composition were not affected. Because of the apparent resistance of the small, dense LDL to drug-induced modifications, a maximal lipid-lowering effect is needed to reduce coronary risk in FCHL patients.
 ...
PMID:Pravastatin effectively lowers LDL cholesterol in familial combined hyperlipidemia without changing LDL subclass pattern. 791 6

Familial defective apolipoprotein B-100 (FDB) is a genetic disorder resulting from a mutation in the apolipoprotein B-100 (apo B-100) gene, most frequently at position 3500, in which arginine is substituted for glutamine in the mature protein. This mutation drastically decreases the affinity of the mutant apo B-100 particle for the low-density lipoprotein (LDL) receptor, and hence decreases the clearance of cholesterol from the circulation. Familial hypercholesterolemia (FH), also a disorder of lipid metabolism, results from mutations in the gene for the LDL receptor. Both FDB and heterozygous FH occur at approximately the same frequency (1 in 500) among Caucasians and both produce clinical symptoms and signs that can be indistinguishable. Polymerase chain reaction (PCR) amplification and subsequent restriction analysis have been used to detect the substitution at codon 3500 in the apo B-100 gene using mutagenic PCR primers. At least one proband from 10 unrelated families with a history of hypercholesterolemia was screened by mutagenic PCR for FDB. Only one of 10 patients demonstrated the mutation for FDB. The mutant apo B-100 allele was shown to segregate with other clinically affected family members. These results demonstrate that molecular analysis is essential to distinguish between FDB and heterozygous FH in hypercholesterolemic families.
 ...
PMID:Detection of familial defective apolipoprotein B-100 among patients clinically diagnosed with heterozygous familial hypercholesterolemia in maritime Canada. 800 Dec 87

Familial combined hyperlipidemia (FCHL) is a common inherited lipid disorder, affecting 1 to 2 percent of the population in Westernized societies. Individuals with FCHL have large quantities of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) and develop premature coronary heart disease. A mouse model displaying some of the features of FCHL was created by crossing mice carrying the human apolipoprotein C-III (APOC3) transgene with mice deficient in the LDL receptor. A synergistic interaction between the apolipoprotein C-III and the LDL receptor defects produced large quantities of VLDL and LDL and enhanced the development of atherosclerosis. This mouse model may provide clues to the origin of human FCHL.
 ...
PMID:A mouse model with features of familial combined hyperlipidemia. 899 37

We previously described a Sardinian family in which the probands had a severe form of hypercholesterolemia, suggestive of familial hypercholesterolemia (FH). However, low density lipoprotein (LDL) receptor activity in fibroblasts from these subjects and LDL binding ability were normal. The characteristics of the pedigree were consistent with an autosomal recessive trait. Sitosterolemia and pseudohomozygous hyperlipidemia were ruled out. A second Sardinian kindred with similar characteristics was identified. Probands showed severe hypercholesterolemia, whereas their parents and grandparents were normolipidemic. FH, familial defective apoprotein (apo) B, sitosterolemia, and cholesteryl ester storage disease were excluded by in vitro studies. We addressed the metabolic basis of this inherited disorder by studying the in vivo metabolism of LDL in 3 probands from these 2 families. 125I-LDL turnover studies disclosed a marked reduction in the fractional catabolic rate (0.19+/-0.01 versus 0.36+/-0.03 pools per day, respectively; P<0.001) and a significant increase in the production rate [20.7+/-4.4 versus 14. 0+/-2.4 mg. kg-1. d-1, respectively; P<0.01] of LDL apoB in the probands compared with normolipidemic controls. We then studied the in vivo biodistribution and tissue uptake of 99mtechnetium-labeled LDL in the probands and compared them with those in normal controls and 1 FH homozygote. The probands showed a significant reduction in hepatic LDL uptake, similar to that observed in the FH homozygote. A reduced uptake of LDL by the kidney and spleen was also observed in all patients. Our findings suggest that this recessive form of hypercholesterolemia is due to a marked reduction of in vivo LDL catabolism. This appears to be caused by a selective reduction in hepatic LDL uptake. We propose that in this new lipid disorder, a recessive defect causes a selective impairment of LDL receptor function in the liver.
 ...
PMID:Characterization of a new form of inherited hypercholesterolemia: familial recessive hypercholesterolemia. 1007 89

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by elevated low-density lipoproteins (LDL), the formation of tendon and skin xanthomata and the development of premature coronary atherosclerosis. It is caused by a defect in the receptor-mediated hepatic uptake of LDL due to mutations in the LDL receptor. In 25 FH families with a total of 160 members and in two individuals without available relatives, all of German origin, we identified LDL receptor mutations by a multiplex-PCR-based single-strand conformation polymorphism method followed by direct sequencing. Of the 24 mutations found, 15 are missense mutations, 2 are nonsense mutations, 4 are small deletions or insertions leading to frameshifts, 2 are an in-frame insertion and deletion, respectively, and one is a splice site mutation. Propositi carrying mutations that are known to completely abolish receptor function (nonsense and frameshift mutations, missense mutation V480M) had significantly higher untreated total and LDL-cholesterol levels compared to those patients carrying missense and in-frame insertion mutations of unknown functional consequence, which may lead to either reduced or completely abolished receptor function (11.30+/-1.64 vs 9.76+/-1.50 mmol/L, and 9.39+/-1.23 vs 7.99+/-1.45 mmol/L, respectively). These results confirm the clinical and molecular heterogeneity of FH and the influence of different functional classes of mutations on lipid values.
 ...
PMID:Mutations in the low-density-lipoprotein receptor gene in German patients with familial hypercholesterolaemia. 1119 4

Lipoprotein apheresis is an effective treatment for severe disorders of lipid metabolism. It is the only life prolonging therapy for patients with homozygous familial hypercholesterolemia. Changes of lipid metabolism during pregnancy related to changes of hormone concentrations do not cause clinical complications in the majority of cases. However, in particular clinical situations there is the need to offer a therapeutic option. Increasing morbidity and mortality of mother and child due to severe disorders of lipid metabolism have to be prevented. In general, lipid lowering drugs are contraindicated during pregnancy. Therefore, lipoprotein apheresis offers an alternative, which could be used in select cases to treat acute or chronic hyperlipoproteinemia associated with pregnancy. This article summarizes experiences with patients, who became pregnant during chronic lipoprotein apheresis, or who were treated by lipoprotein apheresis because of acute disorders of lipid metabolism during pregnancy. In conclusion, after individual risk benefit analysis for mother and child lipoprotein apheresis can be safely performed during pregnancy.
 ...
PMID:Differential indication of lipoprotein apheresis during pregnancy. 1292 13


1 2 3 Next >>