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)

A study of the relatives of a patient with apolipoprotein C-II deficiency showed that the defect is inherited as an autosomal recessive trait. The kindred studied originated from an isolated population in which considerable inbreeding has occurred for 140 years. Seven homozygotes had marked fasting chylomicronemia and triglyceridemia, and lacked detectable apolipoprotein C-II by several assay methods. Five homozygotes had experienced one to many attacks of pancreatitis from as early as six years of age. Obligate heterozygotes had apolipoprotein C-II concentrations about 30 to 50 per cent of normal values and had normal plasma triglyceride concentrations. This metabolic defect should be considered in patients with markedly elevated plasma triglycerides who have apparent lipoprotein lipase deficiency, and usually also have pancreatitis.
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PMID:Inheritance of apolipoprotein C-II deficiency with hypertriglyceridemia and pancreatitis. 21 19

We have characterized the clinical and biochemical features of three siblings of a kindred with severe hypertriglyceridaemia due to apolipoprotein C-II (apo C-II) deficiency caused by the mutation described as apo C-IIHamburg. The clinical syndrome is characterized by recurrent pancreatitis in two of three affected individuals, with discrete hepatosplenomegaly in all three patients and cholelithiasis in one. Eruptive xanthomas and lipemia retinalis were absent. Plasma lipoproteins were characterized by fasting chylomicronaemia, reduced low density lipoproteins (LDL) and low high density lipoproteins (HDL). The marked hypertriglyceridaemia could be corrected promptly by infusion of normal plasma. Apolipoprotein C-II (apo C-II) levels in homozygotes were very low (0.01 mg dl-1), and mean apo C-II levels in heterozygotes were lower (2.08 +/- 0.11 mg dl-1) than in normal family members (3.38 +/- 0.75 mg dl-1). Lipoprotein lipase and hepatic triglyceride lipase activities in post-heparin plasma were normal. Zonal ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins and reduced LDL and HDL. LDL consisted of two fractions with higher hydrated density of the main fraction compared with normals with a trend to normalization on a fat-free diet. The molecular defect in the apo C-II Hamburg gene has been previously identified as a donor splice site mutation in the second intron. This leads to abnormal splicing of the apo C-II Hamburg mRNA and apo C-II deficiency in plasma. The mutation causes the loss of an HphI restriction enzyme site present in the normal apo C-II gene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein C-II deficiency syndrome due to apo C-IIHamburg: clinical and biochemical features and HphI restriction enzyme polymorphism. 134 86

Two patients (brother and sister, 41 and 39 yr of age, respectively) have been shown to have marked elevation of plasma triglycerides and chylomicrons, decreased low density lipoproteins (LDL) and high density lipoproteins (HDL), a type I lipoprotein phenotype, and a deficiency of plasma apolipoprotein C-II (apo C-II). The male patient had a history of recurrent bouts of abdominal pain often accompanied by eruptive xanthomas. The female subject, identified by family screening, was asymptomatic. Hepatosplenomegaly was present in both subjects. Analytical and zonal ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins including chylomicrons and very low density lipoproteins, a reduction in LDL, and the presence of virtually only the HDL3 subfraction. LDL were heterogeneous with the major subfraction of a higher hydrated density than that observed in plasma lipoproteins of normal subjects. Apo C-II levels, quantitated by radioimmunoassay, were 0.13 mg/dl and 0.12 mg/dl, in the male and female proband, respectively. A variant of apo C-II (apo C-IIPadova) with lower apparent molecular weight and more acidic isoelectric point was identified in both probands by two-dimensional gel electrophoresis. The marked hypertriglyceridemia and elevation of triglyceride-rich lipoproteins were corrected by the infusion of normal plasma or the injection of a biologically active synthesized 44-79 amino acid residue peptide fragment of apo C-II. The reduction in plasma triglycerides after the injection of the synthetic apo C-II peptide persisted for 13-20 d. These results definitively established that the dyslipoproteinemia in this syndrome is due to a deficiency of normal apo C-II. A possible therapeutic role for replacement therapy of apo C-II by synthetic or recombinant apo C-II in those patients with severe hypertriglyceridemia and recurrent pancreatitis may be possible in the future.
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PMID:Apolipoprotein C-II deficiency syndrome. Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients. 394 67

Disorders in lipoprotein metabolism (dyslipidemia) can result in premature atherosclerosis or pancreatitis. Dyslipidemias can be classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low density lipoprotein cholesterol and decreased levels of HDL cholesterol predispose to premature atherosclerosis. Triglyceride levels greater than 1,000 mg/dL increase the risk for pancreatitis. In the appraisal of the dyslipidemias, measurement of serum cholesterol, triglycerides, HDL-cholesterol and obtaining the LDL cholesterol by Friedewald equation is usually sufficient in the majority of patients. However, in some cases, such as the diagnosis of the Type III dyslipidemia and when triglycerides are > or = 400 mg/dL, ultracentrifugation is required to determine the VLDL or LDL cholesterol. Lipoprotein electrophoresis can be useful in the diagnosis of Type III dyslipidemia (broad beta band) and also to detect chylomicrons. In young subjects with coronary artery disease with a normal LDL cholesterol an apolipoprotein B-100 level may be a useful test. In children and young adults with severe hypertriglyceridemia, measurement of lipoprotein lipase activity or assaying apolipoprotein C-II levels can be useful in elucidating the cause. Also, laboratory tests are useful in excluding a secondary cause of dyslipidemia (urinalysis, plasma creatinine, TSH, glucose, protein electrophoresis, alkaline phosphatase and transaminases). Thus, laboratory investigations play an important role in the management of dyslipidemia.
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PMID:A practical approach to the laboratory diagnosis of dyslipidemia. 870 23

The chylomicronemia syndrome is a disorder characterized by severe hypertriglyceridemia and massive accumulation of chylomicrons in plasma. This hypertriglyceridemia can lead to the development of eruptive xanthomas, lipemia retinalis, and is clinically important when plasma triglyceride levels predispose to pancreatitis (above 2000 mg/dl). Three genetic disorders have been described in which chylomicrons accumulate in plasma: familial lipoprotein lipase deficiency, familial apolipoprotein C-II deficiency, and familial inhibitor to lipoprotein lipase. In addition, chylomicronemia is seen in other states with the simultaneous occurrence of familial forms of moderate hypertriglyceridemia and other acquired causes for hypertriglyceridemia such as diabetes mellitus, certain drug therapies and alcohol use. Treatment should be directed at both the familial and the acquired disorder. This review discusses the chylomicronemia syndrome presenting the pathophysiologic characteristics of triglyceride and chylomicrons metabolism, diagnosis, prevalence and treatment.
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PMID:[Chylomicronemia syndrome]. 1190 95

A 56-year-old male with apolipoprotein C-II deficiency experienced a myocardial infarction without pancreatitis. A coronary angiogram showed complete occlusions of both the right and circumflex coronary arteries. His serum lipid levels were as follows: fasting total cholesterol 3.15 mmol/l; postprandial total cholesterol 3.62 mmol/l; fasting triglycerides 1.46 mmol/A; postprandial triglycerides 6.14 mmol/l; fasting high-density lipoprotein-cholesterol 0.47 mmol/l; and postprandial high-density lipoprotein cholesterol 0.36 mmol/l. His fasting level of plasma apolipoprotein C-II was 0.005 g/l, but his plasma levels of other apolipoproteins were within normal ranges. A DNA sequence analysis of the apolipoprotein C-II gene showed no mutations in exon 1, 2, 3, or 4, where most gene mutations related to apolipoprotein C-II deficiency occur. We report this patient's very rare heterozygous apolipoprotein C-II deficiency with coronary artery disease. Although this patient had some risk factors for coronary artery disease, coronary atherosclerosis in this patient might have occurred as a result of lipoprotein abnormalities caused by at least one mutation in the apolipoprotein C-II gene.
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PMID:A case of apolipoprotein C-II deficiency with coronary artery disease. 1204 86

Acute and chronic recurrent pancreatitis have been reported in patients with a variety of inborn errors of metabolism. Among these are hyperlipidaemias, various disorders of branched-chain amino acid degradation, homocystinuria, haemolytic disorders, acute intermittent porphyria and several amino acid transporter defects. Some of these disease entities are exceedingly rare. In most of these disorders, pancreatitis is not very common and, with the exception of lipoprotein lipase and apolipoprotein C-II deficiency, is neither the leading nor the clinically most distressing manifestation of the underlying metabolic defect. The majority of these syndromes are, however, inherited, and often entire kindreds are carriers of well-defined germline mutations that can, to varying degrees, be associated with pancreatitis. We have reviewed the clinical, biochemical and genetic characteristics of those inborn errors of metabolism because interesting information can be gained from the in regard to the pathophysiology of pancreatitis and because they need to be distinguished from other hereditary causes of the disease.
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PMID:Acute and chronic pancreatitis in patients with inborn errors of metabolism. 1212 Feb 23

A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes.
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PMID:A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis. 1643 Dec 16

A case of chylomicronemia syndrome is reported in a 72-year-old male with distinctive features of chronic pancreatic damage, severe hypertriglyceridemia, polidistrectual atherosclerosis and premature cognitive impairment. Although the patient had a positive history for recurrent episodes of pancreatitis the characteristic lesions of the hyperchylomicronemia syndrome, such as eruptive xanthomas and lipemia retinalis, were not present and splenomegaly could not be documented due to a previous post-traumatic splenectomy. Based on clinical phenotype, an apolipoprotein C-II deficiency was excluded by a fresh plasma infusion test, in which clarification of the patient plasma was not obtained. The absence of changes in the lipoprotein electrophoretic plasma after heparin infusion can be secondary to a lipoprotein lipase deficiency, a rare genetic disorder with an incidence of one per million. In relation to the resistance to diet and drugs, plasma exchange therapy was performed. After 3 years of this treatment there was no significant progression of atherosclerosis.
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PMID:Cognitive impairment and polidistrectual atherosclerotic disease in chylomicronemia syndrome: a case report. 2387 65

This Review discusses new developments in understanding the basis of chylomicronaemia--a challenging metabolic disorder for which there is an unmet clinical need. Chylomicronaemia presents in two distinct primary forms. The first form is very rare monogenic early-onset chylomicronaemia, which presents in childhood or adolescence and is often caused by homozygous mutations in the gene encoding lipoprotein lipase (LPL), its cofactors apolipoprotein C-II or apolipoprotein A-V, the LPL chaperone lipase maturation factor 1 or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1. The second form, polygenic late-onset chylomicronaemia, which is caused by an accumulation of several genetic variants, can be exacerbated by secondary factors, such as poor diet, obesity, alcohol intake and uncontrolled type 1 or type 2 diabetes mellitus, and is more common than early-onset chylomicronaemia. Both forms of chylomicronaemia are associated with an increased risk of life-threatening pancreatitis; the polygenic form might also be associated with an increased risk of cardiovascular disease. Treatment of chylomicronaemia focuses on restriction of dietary fat and control of secondary factors, as available pharmacological therapies are only minimally effective. Emerging therapies that might prove more effective than existing agents include LPL gene therapy, inhibition of microsomal triglyceride transfer protein and diacylglycerol O-acyltransferase 1, and interference with the production and secretion of apoC-III and angiopoietin-like protein 3.
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PMID:Chylomicronaemia--current diagnosis and future therapies. 2573 19


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