Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type V hyperlipoproteinemia (HLP) is characterized clinically by hepatosplenomegaly, occasional eruptive xanthomas, and an increased incidence of pancreatitis. These patients have striking hypertriglyceridemia due to increased plasma chylomicron and very low density lipoprotein concentrations in the fasting state, without a deficiency of lipoprotein lipase or its activator protein, apolipoprotein (apo) C-II. ApoE, a protein constituent of triglyceride-rich lipoproteins, has been implicated in the receptor-mediated hepatic uptake of these particles. ApoE has three major alleles: E2, E3, and E4, and the products of these alleles are apoE2, apoE3, and apoE4, respectively. ApoE phenotypes were determined in 30 type V HLP patients as well as in 37 normal volunteers. Among the type V patients, 33.3% were noted to be homozygous, and 40.0% heterozygous for E4 (normal, 2.7 and 21.6%, respectively). These data suggest that apoE4 may play a role in the etiology of the hyperlipidemia in a significant number of type V HLP patients.
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PMID:Increased prevalence of apolipoprotein E4 in type V hyperlipoproteinemia. 709 73

Primary deficiency of the enzyme lipoprotein lipase (LPL) is an autosomal recessive disorder characterized by chylomicronemia, recurrent pancreatitis and xanthomas. In recent years, a growing number of mutations have been identified in patients with this inherited disorder and molecular defects include insertions and deletions, splicing defects, and nonsense and missense mutations. Most of these mutations are clustered in the region encoded by exon 4, 5 and 6 which forms the catalytic domain of LPL. The study of these mutations also contributes to our understanding of the structure, function relationships of the enzyme.
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PMID:[Primary lipoprotein lipase deficiency: clinical and genetic aspects]. 785 14

Apo C-II has a central role in triglyceride metabolism as a cofactor for lipoprotein lipase (LPL), the enzyme that catalyzes the hydrolysis of triglycerides on plasma lipoproteins. Apo C-II deficiency is a rare genetic disorder that is inherited as an autosomal recessive trait. Patients with this syndrome have marked alterations of triglyceride metabolism which include elevated fasting triglycerides, chylomicrons, and VLDL. Clinical features also include lipemia retinalis, eruptive xanthomas, and an increased incidence of pancreatitis. The initial description of the first patient with apo C-II deficiency by Breckenridge et al. established the important role of apo C-II as a cofactor for LPL. Since then, many kindreds with apo C-II deficiency have been described and the underlying molecular defect characterized.
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PMID:[Apolipoprotein C-II deficiency]. 785 17

A now 24-year-old woman was found at the age of 2 years to have an hyperchylomicronaemia syndrome due to lipoprotein lipase deficiency: the triglyceride level was then 6000 mg/dl. But in subsequent years it had been reduced to between 550 and 2600 mg/dl by dieting. There were no xanthomas or abdominal symptoms during those years. When aged 20 years she was put on oral contraceptives (one-phase preparation: 0.03 mg ethinylestradiol and 0.075 gestodene). Six months later she had the first attack of severe necrotizing pancreatitis; three more attacks followed in the subsequent 6 months. All four attacks occurred during the drug-free period of the menstrual cycle. The relationship with contraceptive intake was not established until the fourth attack. The last acute pancreatitis (lipase 3283 U/l amylase 595 U/l, triglyceride 2400 mg/dl, WBC count 13,899/microliters; ultrasonography revealed fluid swelling and necrotic areas, especially around the splenic hilus) regressed within 5 days and has not recurred for 3 years after the patient stopped taking oral contraceptives. On a diet the triglyceride level has been around 880 mg/dl.
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PMID:[Oral contraceptive-induced pancreatitis in the hyperchylomicronemia syndrome]. 787 68

We analyzed the molecular defects in the lipoprotein lipase gene of a patient with type I hyperlipidemia suffering from recurrent pancreatitis, indicative for lipoprotein lipase deficiency. Postheparin lipoprotein lipase activity in the patient was decreased by 70%. Direct genomic sequencing revealed compound heterozygosity for two mutation: the well-known Gly188-->Glu and a new Val69-->Leu substitution. Val69 is situated in a conserved hydrophobic region of the lipoprotein lipase protein, and the substitution with leucine gives rise to a 80% decrease in specific catalytic activity, as supported by site-directed mutagenesis experiments, followed by expression in COS-cells. The combination of both defects in the lipoprotein lipase gene was incidentally associated with severe clinical expression of disease, and triglyceride levels of more than 30 mmol/l were measured. In our patient, triglyceride levels wer usually below 10 mmol/l. We, therefore, postulate that the residual LPL activity in our patient is usually sufficient to keep the triglyceride level within bounds and expression of disease occurred only when conditions such as alcohol abuse or poor compliance to diet were present.
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PMID:A compound heterozygote for lipoprotein lipase deficiency, Val69-->Leu and Gly188-->Glu: correlation between in vitro LPL activity and clinical expression. 791 54

We report the molecular basis of familial chylomicronemia and recurrent pancreatitis in five members of a large Dutch family. All patients had normal plasma hepatic lipase and apoC-II levels, but absent lipoprotein lipase (LPL) catalytic activity and low LPL mass in postheparin plasma. The mutation in the LPL gene was characterized as a G715-->A substitution in the last nucleotide of exon 4, resulting in a substitution of Ser for Gly154. PCR amplification of exons 4 + 5 from the patients' mRNA, followed by direct sequencing, revealed normal splicing of intron 4. The mutation creates a BfaI restriction site that allows rapid screening of family members for the mutation. Reproduction of this mutation in LPL-cDNA by site-directed mutagenesis, followed by transient expression in COS-B cells, revealed production of a catalytically inactive enzyme. The Gly154-->Ser substitution appears in a conserved beta-sheet region, in close proximity to Asp156, which is part of the catalytic triad. These studies show that changes to residues close to Asp156 can have profound effects on catalytic activity of LPL.
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PMID:Recurrent pancreatitis and chylomicronemia in an extended Dutch kindred is caused by a Gly154-->Ser substitution in lipoprotein lipase. 830 Dec 30

A proband with chylomicronemia, pancreatitis, and non-insulin-dependent diabetes (NIDDM) bears two different mutations in exon 3 of the lipoprotein lipase (LPL) gene: a missense mutation, 75Arg-->Ser, inherited through the paternal line and a truncation, 73Tyr-->Ter, through the maternal line. NIDDM appeared to be independently segregating. The R75S mutant was studied in extracts and media from transfected COS-1 cells. Detectable amounts of catalytically competent R75S LPL suggested destabilization of the active homodimer as with exon 5 mutants (Hata et al. 1992. J. Biol. Chem. 267:20132-20139). Hydrolysis of a short-chain fatty acid ester indicated that R75S does not directly affect activation of LPL by apoC-II. Subjects with NIDDM and wild-type LPL, and nondiabetic middle-aged carriers of the 73Tyr-->Ter truncation had moderate hypertriglyceridemia (260-521 mg/dl) and reduced high density lipoprotein cholesterol. A maternal aunt with NIDDM carried the truncation. Her phenotype (triglycerides of 5,300 mg/dl, eruptive xanthomatosis, and recurrent pancreatitis) was as severe as that in homozygotes or compound heterozygotes. We conclude: (a) diabetic carriers of dysfunctional LPL alleles are at risk for severe lipemia; and (b) the physiologic defects in NIDDM may be additive or synergistic with heterozygous LPL deficiency.
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PMID:Mutations in exon 3 of the lipoprotein lipase gene segregating in a family with hypertriglyceridemia, pancreatitis, and non-insulin-dependent diabetes. 832 86

The familial hyperchylomicronaemia syndrome is a hereditary disorder of lipoprotein metabolism caused by lipoprotein lipase (LPL) deficiency, apolipoprotein(apo) CII deficiency or LPL inhibition. This syndrome, which is characterized by hyperchylomicronaemia, attacks of epigastric pain, recurrent pancreatitis and the presence of eruptive xanthomas, may ultimately lead to necrotizing pancreatitis or pancreatic insufficiency. Treatment consists of lifelong adherence to a low-fat diet to prevent hyperchylomicronaemia and its sequelae. We describe here the clinical course of a patient with acute pancreatitis due to hyperchylomicronaemia based on hereditary LPL deficiency. The different causes of the familial hyperchylomicronaemia syndrome and its therapy will be discussed and an update is presented of our knowledge concerning the basic molecular defects of this hereditary disorder.
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PMID:The familial hyperchylomicronaemia syndrome. 844 22

Normal pregnancy is associated with a two- to threefold increase in plasma triglyceride levels, particularly in the third trimester, due both to the overproduction of VLDLs and to the possible suppression of lipoprotein lipase (LPL) activity. Numerous mutations in the human LPL gene causing complete LPL deficiency have been described, but naturally occurring mutations that result in defective LPL with partial activity have not yet been reported. Here we describe a 30-yr-old woman who was first diagnosed with LPL deficiency during pregnancy after she developed pancreatitis. Her plasma triglyceride levels remained mildly elevated at approximately 300 mg/dl (3.4 mmol/liter) after the first pregnancy but rose significantly after she became pregnant again (1800 to 2000 mg/dl) (20.2 to 22.5 mmol/liter). DNA sequence analysis of the LPL gene showed that the patient is homozygous for a Ser172-->Cys missense mutation in exon 5. In vitro mutagenesis revealed that the Ser172-->Cys mutation caused a mutant LPL protein that had residual activity higher than that seen in all eight other missense mutations in patients with LPL deficiency identified in our laboratory. We propose that some mutations in the LPL gene produce a defective LPL with partial activity, which usually leads to mild hypertriglyceridemia.
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PMID:Gene-environment interaction in the conversion of a mild-to-severe phenotype in a patient homozygous for a Ser172-->Cys mutation in the lipoprotein lipase gene. 848 65

Primary lipoprotein lipase deficiency is a rare autosomal recessive disease that causes hyperchylomicronaemia complicated by pancreatitis. Recent advances in molecular biology have facilitated its diagnosis and enabled heterozygous subjects to be identified. Numerous mutations are responsible for lipoprotein lipase deficiency. In some eastern regions of Quebec province homozygotes have been found in very high concentrations: up to 200 times the frequency observed in all other parts of the world. Heterozygocity may represent 1 in 40 subjects. Two mutations account for 95 percent of the Quebec cases, and each of them has its own characteristic geographical distribution. These peculiarities have been ascribed to a founder effect suggested by the analysis of the first colons' migrations and by the study of homozygotes' genealogy. Most of the ancestors of the Quebec carriers came from northwestern France in the 17th century, and heterozygotes alleged to be healthy carriers of the trait may have a predisposition to premature development of a cardiovascular disease. Their blood lipid levels and the composition of their lipoproteins (particularly those with low density) are suggestive of an atherogenic potential similar to that of hyperapobetalipoproteinaemia or familial combined hyperlipidaemia. Molecular biology would be a useful tool to confirm or infirm this hypothesis and to identify subjects at risk of developing a cardiovascular disease.
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PMID:[Primary lipoprotein lipase deficiency. Study in Quebec]. 851 Nov 35


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