Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K1 resulted in the normalization of these coagulation factors. After taking liver biopsies it was demonstrated that the coagulation abnormality was accompanied by a defective gamma-glutamyl-carboxylase, which had a decreased affinity for both vitamin K hydroquinone and propeptide. This observation prompted us to study in a well-defined in vitro system the possible allosteric interaction between the propeptide binding site and the vitamin K hydroquinone binding site on carboxylase. It was shown that by the binding of a propeptide-containing substrate to gamma-glutamylcarboxylase the apparent KM for vitamin K hydroquinone is decreased about 20-fold. On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully explained.
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PMID:Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats. 145 98

The second step in the pathway for synthesis of bile acids from cholesterol is catalysed by the enzyme 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase. Deficiency of this enzyme has been reported to produce cholestatic liver disease with progressive cirrhosis. Treatment with chenodeoxycholic acid led to clinical and biochemical improvement in one patient. We report a further child with this disorder who presented with prolonged neonatal jaundice followed by symptoms of malabsorption of fat-soluble vitamins. Bile acid replacement therapy resulted in clinical and biochemical improvement; it was also possible to demonstrate improvement in the histological appearance of the liver biopsy 4 months after commencing treatment.
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PMID:3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency; effect of chenodeoxycholic acid therapy on liver histology. 158 74

The alpha 1-antitrypsin deficient subject (protease inhibitor (PI) phenotype ZZ) has an increased susceptibility to liver disease. The condition is most commonly identified in early infancy as a conjugated hyperbilirubinaemia with hepatitis (11%) or a bleeding state due to vitamin K malabsorption (2%). 50% of cases have cirrhosis and 25% die in the first decade of life. A further 2% present with cirrhosis in later childhood. Adult males are at risk of hepatoma development with or without cirrhosis. Diagnosis is by isoelectric focussing or allele-specific oligonucleotide hybridization. The treatment is that of cholestasis and cirrhosis including transplantation. The pathobiology of the deficiency state, the mechanism of liver damage and the vulnerability of the newborn liver are discussed in this review. A plea is made for a trial of infusions of alpha 1-antitrypsin in early infancy, as is used safely but without proven efficacy in the emphysematous PIZZ subject. Prospects of therapy by gene modification are also reviewed.
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PMID:Alpha 1-antitrypsin deficiency and liver disease: clinical presentation, diagnosis and treatment. 174 15

The alimentary surveys carried out on various sectors of the population in industrialized countries have shown the existence of chronic clinically silent deficiency in micronutrients. In some cases, as in folates, their lability against conservation techniques, the change in alimentary habits, the abuse of alcohol and the great quantity of frequently used drugs which interfere in their absorption, diminish their content in the diet and their bio-availability. The appearance of macrocytic anemia is a late deficiency sign, and therefore in situations of an increase need and in patients included in the risk groups, a supplemental intake must be given in order to avoid irreversible lesions if it is not possible to monitor the folate levels. There are risk groups in which various etiological factors come into play, acting at a different metabolic level on the folates and making more difficult their dietetic or pharmacological compensation even if supply is considerably increased. We studied these factors independently and in each specific situation (old people, patients with liver disease, alcoholics, pregnant women and nursing mothers, neonates, children, malabsorption syndromes, gastrectomy, AIDS, anaesthesia and patients being treated with antifolic medication), evaluating their mechanisms of action and their potentiation in determined specific situations.
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PMID:[Folates in human nutrition, Different clinical situations in which folate deficiencies exist]. 176 30

Little information has been reported on the metabolic characteristics of the totally pancreatectomized patient or the efficacy of medical management after radical pancreatic surgery. The prospective evaluation of 49 such patients, with 31% followed for 48 or more months, forms the basis of this report. The major immediate postoperative challenge is control of diarrhea and weight stabilization. Chronically patients have an increased daily caloric requirement (mean +/- SE, 56 +/- 1 kcal/kg), not wholly explained by moderate steatorrhea (fecal fat excretion, 16% +/- 2% of unrestricted fat intake). Despite persistent malabsorption, deficiencies in fat-soluble vitamin, magnesium, and trace element serum levels can be prevented in most patients. Pancreatogenic diabetes is characterized by (1) absence of the major glucoregulatory hormones insulin and glucagon, (2) instability, and (3) frequent hypoglycemia, with the latter parameters improving with rigorous home glucose monitoring. No patient has developed clinically overt diabetic micro- or macrovascular disease. Performance status in long-term survivors has been reasonable. However adverse chronic sequelae of the operation occur and include an unusual frequency of liver disease, characterized by accelerated fatty infiltration, and osteopenia, with an 18% reduction in radial bone mineral content noted in pancreatectomized patients studied more than 5 years after surgery.
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PMID:Metabolic consequences of (regional) total pancreatectomy. 186 20

While the rate of malnutrition is relatively modest in alcoholic patients without alcoholic liver disease, the rate of malnutrition is virtually 100% in patients with alcoholic hepatitis and/or alcoholic cirrhosis. The reasons for malnutrition in the alcoholic hepatitis patient include various factors such as anorexia, poor diet, malabsorption, and altered metabolic state. When the patient is hospitalized, the malnutrition frequently worsens because of fasting for tests, continued anorexia, and complications such as gastrointestinal bleeding. Patients with severe acute hepatitis appear to be both hypermetabolic and hypercatabolic, whereas data are much more conflicting concerning patients with more stable liver disease. Most studies suggest that patients with alcoholic liver disease require at least 60 g of protein per day to maintain positive nitrogen balance. Consistent alterations in plasma amino acid profiles occur in alcoholic liver disease, and specialized nutritional formulations have been devised to correct this amino acid profile with the intent of improving overall nutritional status, hepatic encephalopathy, and mortality. The effects of nutritional support (including use of specialized products) on outcome, on acute hepatic encephalopathy, and on chronic or latent portal systemic encephalopathy are reviewed.
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PMID:Nutrition and alcoholic liver disease. 190 86

The active transport of conjugated bile acids by the ileum is responsible for the enterohepatic circulation of bile acids, a physiological process that ensures an ample supply to the intestine of these key biological surfactants, irrespective of the rate of their biosynthesis from cholesterol. The ileal bile acid transport system is a high capacity, low affinity secondary active Na+ co-transport system that differs in substrate specificity from that present in the hepatocyte. Ileal transport is homeostatically regulated by feedback inhibition of the bile acids that are transported. The enterohepatic circulation is responsible for the concentration profile present in the intestine--high concentrations in the small intestine and low concentrations in the large intestine. Loss of ileal absorption, when mild, leads to a sequence of events that result in increased concentrations in the large intestine causing diarrhea. Severe bile acid malabsorption causes decreased concentrations in the small intestine which in turn lead to fat maldigestion and fat malabsorption. The increased passage of fatty acids into the colon contributes to diarrhea. Fat maldigestion and malabsorption also causes increased absorption of dietary oxalate from the colon which causes hyperoxaluria and contributes to nephrolithiasis. In cholestatic liver disease, inappropriate upregulation of ileal bile acid transport is likely to cause retention of hepatotoxic endogenous bile acids. In familial hypercholesterolemia, efficient bile acid absorption contributes to downregulation of LDL receptors and the maintenance of elevated plasma cholesterol levels; upregulation of bile acid transport during bile acid sequestrant therapy could diminish its efficacy. Efforts are in progress to develop a suitable bile acid analogue to be administered orally for conditions of bile acid deficiency in the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biological and medical aspects of active ileal transport of bile acids. 206 93

The prevalence, type, and factors that may influence the development of bone disease in primary biliary cirrhosis, have been investigated in 20 consecutive patients, who, in addition to liver function tests and mineral and vitamin D metabolism studies, were submitted to a transiliac bone biopsy after tetracycline double-labeling for quantitative histomorphometric examination. Intestinal calcium absorption was also assessed in 16 patients. Seven patients (35%) had reduced bone volume and were considered osteoporotic. Three also had bone mineralization impairment, but did not have criteria for osteomalacia. Bone formation was depressed in 15 patients, and bone resorption was low or normal in 19 cases. Eroded surfaces were reduced in all osteoporotic patients. Duration of primary biliary cirrhosis was significantly longer in patients with osteoporosis (6.3 +/- 0.6 yr) than in those without osteoporosis (2.6 +/- 0.6, p = 0.004). Moreover, osteoporosis was more prevalent in postmenopausal women, and in those who had intestinal calcium malabsorption, which was present in 80% of osteoporotic patients but in only 18% of nonosteoporotic patients (p = 0.03). Osteoporosis and mineralization bone impairment were unrelated to the severity of cholestasis. 25-Hydroxyvitamin D was significantly lower in those patients with intestinal calcium malabsorption. The results of this study indicate that osteodystrophy in primary biliary cirrhosis is characterized mainly by "low-turnover" osteoporosis, which is related to the duration of the liver disease, postmenopausal condition, and calcium malabsorption.
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PMID:Factors influencing the development of metabolic bone disease in primary biliary cirrhosis. 222 Jul 29

Fractional absorption of calcium was determined in 9 children aged 4.9 to 16.9 yr with chronic cholestatic liver disease to determine the role of calcium malabsorption in the development of metabolic bone disease. Radiological evidence of rickets was absent in all patients, but bone density, measured by single beam photon absorptiometry of the distal radius, was reduced in eight of nine subjects. Serum calcium and phosphorus concentrations were normal in all except one subject. Serum 25-hydroxyvitamin D concentration was decreased compared with controls in only one of nine patients, but serum 1,25-dihydroxyvitamin D concentrations were diminished in seven of nine subjects. In all subjects, dietary calcium and phosphorus intakes were greater than 80% of the RDA. Fractional absorption of calcium, determined by oral and intravenous administration of stable calcium isotopes, was similar in cholestatic compared with control subjects (37.1% +/- 12.5% vs. 34.0% +/- 16.4%). In the cholestatic subjects, calcium absorption correlated with serum 1,25-dihydroxyvitamin D (r = 0.871, p less than 0.002) but not 25-hydroxyvitamin D concentrations. Calcium balance, assessed by the duplicate diet method, was positive in four of five subjects. Anthropometric measurements were performed to examine the relationship between nutritional status and bone mineral content. Heights of all subjects were less than or equal to the 10th percentile and fat stores and somatic protein stores were less than the 25th percentile in six of nine subjects. We conclude that factors other than calcium malabsorption and decreased serum 25-hydroxyvitamin D concentration contribute to diminished bone mass in children with cholestatic liver disease.
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PMID:Calcium absorption in bone disease associated with chronic cholestasis during childhood. 222 18

Deficiency of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, the second enzyme in the sequence that catalyses the synthesis of bile acids from cholesterol, leads to chronic liver disease in childhood as well as to malabsorption of fat and fat soluble vitamins. A 4 year old boy with this condition has been successfully treated by oral administration of a bile acid--chenodeoxycholic acid. He had been jaundiced since birth, grew poorly because of rickets, and had severe pruritus. Plasma transaminase activities were persistently raised. Chenodeoxycholic acid 125 mg twice daily for two months, and then 125 mg daily, cured his jaundice and pruritus, returned his transaminase activities to normal, and eliminated the need for calcitriol for prevention of rickets. On this treatment he has so far remained well for two years. A diagnosis of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency should be considered in any child with unexplained chronic hepatitis or cirrhosis, especially if the liver disease is accompanied by a clinically obvious malabsorption of fat soluble vitamins. A simple colorimetric test of the urine confirms the diagnosis and effective treatment can be started.
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PMID:Treatment of chronic liver disease caused by 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency with chenodeoxycholic acid. 224 2


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