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)

The ability to recognize diverse clinical forms of xanthomas, such as tuberous, planar, eruptive and tendinous, is important in the detection of underlying systemic disease. A variety of primary genetic disorders, as well as numerous secondary conditions such as diabetes, obstructive liver disease, thyroid disease, renal disease, and pancreatitis, can lead to hyperlipoproteinemia that results in the formation not only of xanthomas but also of life-threatening vascular atherosclerosis. An understanding of the pathogenesis of the underlying lipoprotein alterations provides a rational approach to therapy utilizing dietary manipulations and drugs. Such treatment is capable of correcting most disorders of lipid metabolism, and, if appropriate therapy is initiated at the first sign of xanthoma evolution, it may prevent progression of atherosclerosis, provide resolution of xanthomas, and in some instances prevent serious pancreatitis.
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PMID:Xanthomas and hyperlipidemias. 403 Nov 42

The cutaneous markers associated with dyslipoproteinemia are reviewed in the context of the current view of lipid and lipoprotein metabolism. The utility of determining the plasma levels of lipoproteins and certain apoproteins in children or adults with xanthomas or xanthelasma is discussed. We hope that early identification and appropriate treatment of such patients will reduce the morbidity and mortality from the two major complications of dyslipoproteinemia--atherosclerotic cardiovascular disease and pancreatitis.
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PMID:Dyslipoproteinemia and xanthomatosis. 643 4

Specific physical findings are associated with the different phenotypes of hyperlipoproteinemia and may point up the need for further medical work-up to determine whether hyperlipoproteinemia is primary or secondary. The clinical manifestations of severe elevations in plasma lipid levels include xanthomas, which may be tendinous, tuberous, or eruptive. Xanthelasma is a common type of xanthoma that is seen in the creases of the eyelids. Other clinical manifestations of hyperlipoproteinemia include corneal arcus, lipemia retinalis, abdominal pain and pancreatitis. In patients with certain types of xanthoma whose serum cholesterol and triglyceride levels are normal, hyperlipoproteinemia has been diagnosed on the basis of abnormalities in plasma apoproteins and their subfractions.
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PMID:Clinical diagnosis of hyperlipoproteinemia. 684 79

A both useful and simple classification of primary hyperlipidemias must be at the disposal of all medical doctors, namely general practitioners and cardiologists. The practical classification we have proposed and published since 1971, fulfills this aim. Three main frames of hyperlipidemias are individualized: 1) pure or essential hypercholesterolemia 2) mixed or combined hyperlipidemias 3) major hyperglyceridemia: either exogenous or endogenous. In each of these frames, some clinical specific features, as well as some very simple biologic characteristics allow sometimes an immediate orientation towards some definite varieties of primary hyperlipidemias, now perfectly identified at the level of molecular genetic (tendinosum xanthoma with or without planar xanthomas, palm creases syndrome, tuberous or tubero eruptive xanthomas, etc...). Similarly, occurrence of cardiovascular complications, chiefly coronary, in a rather early age, and with a striking repetition in other members of family, as well of attacks of acute or subacute pancreatitis in other forms, helps considerably for orientation of the diagnosis. For all these reasons, systematic reconstitution of genetic tree on, at least, three generations in absolutely necessary. Prevalence, in various populations, of the genetic origin of these various primary disorders of lipid metabolism is round one out of 500 at the heterozygote state. Even if all the genes candidates are not yet finished to be identified, much of them are now perfectly known, in their localisation on DNA and in their multiple mutations. Possibility of combination of different gene defects can be also met; and more and more are described. This extraordinary and explosive knowledge in this field is now to be described.
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PMID:[Frameworks of recognition and classification of primary hyperlipidemia]. 807 78

Familial apolipoprotein (apo) CII deficiency is a rare autosomal recessive inborn error of metabolism clinically resembling lipoprotein lipase deficiency. A number of mutations of the apo CII gene are known to date; they are located in the promoter region, the coding exons, or in the splice junctions. We present a simple assay based on PCR and denaturing gradient gel electrophoresis, which allows scanning of the promoter, the entire coding sequence, and the splice junctions of the apo CII gene for sequence variants. All gene fragments are amplified using a common PCR protocol and are examined for mutations on a single gradient gel. Using this method and direct sequencing, we identified homozygosity for a donor splice-site mutation in the second intron, previously designated apo CII-Hamburg, as the genetic cause of apo CII deficiency in a 9-year-old boy presenting with chylomicronemia, eruptive xanthoma, and pancreatitis. In addition, the method allowed us to detect all of six different other known mutations of the apo CII gene. We conclude, therefore, that our assay is highly sensitive; in addition, it is easy to perform and may facilitate the differential diagnosis of disorders of lipoprotein metabolism at the genetic level.
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PMID:Detection of mutations in the apolipoprotein CII gene by denaturing gradient gel electrophoresis. Identification of the splice site variant apolipoprotein CII-Hamburg in a patient with severe hypertriglyceridemia. 966 14

Because hyperlipidemia may present as xanthomas, a dermatologist may be the first to diagnose these skin lesions and associated lipid abnormalities. Xanthomas are of concern because of their association with coronary artery disease and pancreatitis. We describe the case of a 40-year-old white male with chest pain and eruptive xanthomas. Laboratory tests revealed severe hypercholesterolemia, hypertriglyceridemia, and diabetes mellitus, and the histopathology of the skin lesions was consistent with eruptive xanthomas. Surprisingly, even with overwhelming risk factors for both atherosclerosis and pancreatitis, this patient did not show evidence of either disease process. After initiating therapy for the diabetes and hyperlipidemia, the patient has had no recurrence of chest pain, and the skin lesions have gradually resolved. The most likely explanation for this patient's pattern of symptoms and laboratory results is the chylomicronemia syndrome, which can be seen in patients with type I or type V hyperlipoproteinemia.
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PMID:Eruptive xanthomas and chest pain in the absence of coronary artery disease. 1132 91

Xanthoma and xanthelasma are typical symptoms of lipid and lipoprotein metabolism impairment. On the basis of their incidence and morphology, it is even possible to specify the impairment type. Hypercholesterolemia or certain liver dysfunctions are characterized by slow development of surface xanthelasmas usually located on mechanically stressed regions (e.g. eyelids). Tuberous and tendinous xanthomas are typical for familiar hypercholesterolemia and are common symptoms of homozygous familiar hypercholesterolemia. Small and quickly developing eruptive xanthomas are typical for mixed hyperlipoproteinemia (secondary hyperlipoproteinemia is typical for diabetes). Mechanism of accumulation of lipids in skin morphs is similar to the development of atheroma, especially when talking about the role of modified LDL and the way of accumulation of lipids in macrophages. The following factors are very important for etiopathogenesis of skin xanthomas development: mechanical stress of tissues, increased permeability of skin capillaries and reaction of proteoglycans in sparse connective tissue. Xanthomas and xanthelasmas are typical indicators of other complicating diseases as e.g. development of acute pancreatitis during hyperlipoproteinemic crisis, aggravation of insulin resistance, and decompensation of type 2 diabetes mellitus. The therapy focuses on adjustment of dietary regime (elimination of dietary fat and concentrated saccharides); no food and sufficient hydration via infusion of crystalloid solutions is indicated in cases of serious hyperlipoproteinemic crisis. In vital indication, it is possible to perform repeated plasmapheresis (or better continual plasmapheresis) that can correct even serious hyperlipoproteinemic crises within several hours. And what is more, continual plasmapheresis can significantly reduce the period when hyperlipoproteinemic crisis might induce acute necrotizing pancreatitis. In the long run, we require that patients strictly observe their dietary regime based on the type of hyperlipoproteinemia. As for medicamentous therapy, fibrates and atorvastatin (from statin family) are the preparations of choice. It is very important not to focus on symptoms, i.e. xanthoma or xanthelasma, but fully compensate lipid metabolism impairment or the disease that underlies hyperlipoproteinemia (e.g. type 2 diabetes mellitus or metabolic syndrome). Unfortunately, it still can be seen that dermatologists, ophthalmologists or plastic surgeons remove extensive xanthelasmas, while the underlying cause is not approached diagnostically and therapeutically at all.
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PMID:[Internist's view on skin manifestations of hyperlipidemia in diabetic patients]. 1677 Oct 91

Lipoprotein lipase (LPL) deficiency is a rare autosomal recessive inherited disorder, characterized by marked hypertriglyceridemia, eruptive xanthoma, hepatosplenomegaly, recurrent attacks of pancreatitis, and markedly low or absent LPL activity in postheparin plasma. A majority of LPL deficient patients have been reported to have point mutations in the LPL gene; however, we find a complex deletion-insertion mutation by Alu elements, mobile retrotransposons, in a patient with LPL deficiency. This patient suffered from acute pancreatitis, showed chylomicronemia and lacked detectable LPL activity or mass in her postheparin plasma. Southern blot analysis and long-range PCR of the patient's DNA demonstrated a 2.2-kb deletion encompassing exon 2. Sequence analysis revealed (1) a 2.3-kb deletion between an AT-rich region adjacent to an Alu element in intron 1 and another Alu element in intron 2; (2) an insertion of approximately 150bp 5'-truncated Alu sequence with a poly (A) tail at the deletion point. The inserted sequence belongs to Alu Yb9, the youngest subfamily of Alu elements. The deletion occurred at the consensus cleavage site (3'-A|TTTT-5') without target site duplication. These findings indicated that Alu retrotransposition caused the complex deletion-insertion. The patient was homozygous for this complex mutation, which eliminates exon 2 and leads to LPL deficiency. To our knowledge, the patient is the first case with LPL deficiency due to a complex deletion-insertion mediated by Alu repetitive elements.
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PMID:A novel complex deletion-insertion mutation mediated by Alu repetitive elements leads to lipoprotein lipase deficiency. 1770 45