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)

Hypolipidemias can be divided in primary, familial and hereditary forms and symptomatic forms which may accompany other diseases. The primary hypolipidemias (abetalipoproteinemia, hypobetalipoproteinemia and analphalipoproteinemia) are very rare. Severe hypolipidemia can be found in some peoples (e.g. the Masai). This article is chiefly devoted to secondary hypolipidemias such as those associated with malabsorption, malnutrition and maldigestion including protein-losing gastroenteropathy, with liver diseases, endocrine diseases (hyperthyroidism, hirsutism) and anemia. Finally, the hypolipidemias secondary to the formation of autoantibodies against HDL and LDL in M-gradient, carcinoma and rheumatoid arthritis are briefly reviewed.
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PMID:[Hypolipidemias]. 17 Jun 75

A new kindred with asymptomatic hypobetalipoproteinemia is reported. The proband, age 67, differs from previously described cases in several respects: (a) unusually low levels of low density lipoprotein (LDL) cholesterol (4-8 mg/dl); (b) normal triglyceride levels; (c) low levels of high density lipoprotein; (d) mild fat malabsorption; and (e) a defect in chylomicron clearance. On a high-carbohydrate diet his plasma triglyceride levels, instead of rising, actually fell. Turnover of triglycerides in very low density lipoproteins (VLDL) was low (2.8 mg/kg per h). Fractional catabolic rate of LDL protein was just above the normal range (0.655/d) but net turnover was <10% of normal (0.65 mg/kg per d). The half-life of his chylomicrons was 29 min, five times the normal value. Postheparin lipoprotein lipase activity was normal and apolipoprotein C-II, the activator protein for lipoprotein lipase, was present and functional. Apolipoprotein C-III(1), however, was not detected in the VLDL fraction, a finding previously reported in patients with abetalipoproteinemia. Fecal excretion of cholesterol was almost twice normal; total sterol balance was increased by congruent with40%. The unusual features in the proband that distinguish him from previously described cases and from his affected first-degree relatives suggested that, in addition to the basic gene defect affecting LDL metabolism, he might have a second abnormality affecting clearance of chylomicrons and VLDL. The ratio of apolipoprotein E(3) to E(2) in his VLDL fraction was 0.93, just below the lower limit of normal, suggesting heterozygosity for E(3) deficiency. Whether or not this contributes to his hypertriglyceridemia remains to be established.
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PMID:Metabolic studies in an unusual case of asymptomatic familial hypobetalipoproteinemia with hypolphalipoproteinemia and fasting chylomicronemia. 22 46

A new case of homozygous familial hypobetalipoproteinemia is reported in a 16-yr-old girl. Apoprotein B was absent from plasma and the patient had acanthocytes and steatorrhea, but minimal neurologic dysfunction. Total body cholesterol synthesis was assessed intermittently over a 30-mo period by sterol balance techniques. The rate of synthesis of cholesterol was higher (15.0 +/- 2.9 mg/kg/day) in the patient (8.3 +/- 0.4 mg/kg/day than in 3 control children, p less than 0.005). Bile acid synthesis was similar (4.6 +/- 1.8 versus 4.0 +/- 1.7 mg/kg/day) in the patient and controls, but total body sterol synthesis was significantly higher (19.6 +/- 3.0 versus 12.2 +/- 2.0, p less than 0.005). The absorption of orally administered [1,2,(3)H] cholesterol in the patient was low and less than 0.5% of the label appeared in the total plasma volume at all times up to 48 hr. Estimates of the extent that malabsorption of biliary cholesterol contributes to the enhanced excretion of neutral sterols in this case indicate that all of the increase can be explained on this basis. Thus, although the mechanisms for the increased sterol synthesis in this case may relate to the absence of chylomicrons and low density lipoproteins in plasma, the magnitude of the increase can be fully explained on the basis of a compensatory mechanism to maintain cholesterol homeostasis in the face of enhanced fecal losses.
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PMID:Sterol balance in abetalipoproteinemia: studies in a patient with homozygous familial hypobetalipoproteinemia. 49 73

In a family in which the father was the mother's uncle, 3 of the 7 children were affected by a syndrome of malabsorption with various clinical symptoms. Diarrhea appeared in 2 of the children at birth, and in the third child at six months. The diarrhea led to failure-to-thrive, muscular wasting and abdominal swelling. However, the children improved spontaneously over the years. During childhood all 3 had manifest steatorrhea. Serum cholesterol was between 39 and 100 mg/dl, while triglycerides were normal to high. Reevaluation during the past year revealed areflexia, deficiency of vitamins A and E and of apoproteins A and B, and prolonged PT time in 2 of the children. Electron and light microscopy of small intestinal biopsies revealed vacuoles in the enterocytes. Electrophysiological tests revealed major disturbances in sensory conduction and brain-stem function. These cases differ from those described in the literature. Although in hypobetalipoproteinemia, 1 of the parents would be expected to be heterozygous and have low serum levels of APO B, in this family the parents had normal levels. Their children had low levels of serum APO A, while in patients with hypobetalipoproteinemia the levels are normal. There is a report of a case of deficiencies of both apolipoproteins, but the patient was asymptomatic, had chylomicronemia after a prolonged fast, and lower cholesterol levels than our patients. 8 other cases of apolipoprotein deficiency have been reported with biochemical characteristics similar to those of our patients, but with retention of chylomicrons in the small intestine.
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PMID:[Familial hypobetalipoproteinemia with steatorrhea and malabsorption]. 180 Feb 74

A case of hypobetalipoproteinemia is described; a 16-year-old girl had been suffering for nearly 2 years from diffuse abdominal pain. The only clinical features were liver steatosis, slightly increased amino transferases and an incipient polyneuropathy. No sign of malabsorption or gastrointestinal disease was found. She had extremely low levels of cholesterol and triacylglycerol in her serum, slightly decreased serum phospholipids and normal HDL-cholesterol levels. Apolipoprotein B-100 was approx. 8% of normal, whereas B-48 was present at essentially normal levels. Electron microscopy of lipoprotein particles showed normal morphology of LDL. Examination of close relatives showed no abnormalities. Southern blots revealed no major deletions or rearrangements at the genomic level. Although rare, a- and hypobetalipoproteinemia should be considered as possible etiologies in patients with unexplained steatosis in the liver.
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PMID:Liver steatosis in hypobetalipoproteinemia. A case report. 191 73

A familial study of four cases with hypobetalipoproteinemia is reported. Three members are heterozygous and one is homozygous. This congenital fat malabsorption in homozygous state is commonly associated with an absence of serum apoprotein B and LDL. Neuromuscular and ophthalmological signs are absent in this case. The major role of upper digestive endoscopy in the diagnostic procedure is emphasized. Histochemical and immunoenzymatic stains of enterocytes and intestinal organ culture show defective synthesis apo B in the homozygous patient. Studies of DNA polymorphism in the homozygous patient have shown that the apo B gene doesn't certain major insertions or deletions. These results are discussed.
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PMID:[Familial hypobetalipoproteinemia. Familial study of 4 cases]. 209 30

Eight infants presented with a malabsorption syndrome, normal fasting triglycerides, hypocholesterolemia (64.3 +/- 10.0 mg/dl), and deficiency of vitamins A and E. Plasma low-density lipoprotein, apolipoprotein B, and apolipoprotein A-I were decreased. After a fatty meal, plasma triglycerides did not increase and chylomicrons could not be identified. Lipoprotein composition was characterized by normal apoproteins, high phospholipids, and low cholesterol. Increased triglycerides were present in low-density lipoproteins. Immunoperoxidase localization of apolipoprotein B on fasting biopsy specimens showed increased staining of the lipid-laden intestinal epithelial cells compared to normals. On electron microscopy after a fat load, the enterocytes contained large numbers of fat particles vesiculating the endoplasmic reticulum. These particles, morphologically similar to chylomicrons, were also present as aggregates of well-individualized lipid droplets within dilated vesicles in the Golgi zone, but were not seen in the intercellular spaces and lacteals. This recessively transmitted condition differs from abetalipoproteinemia and from the homozygous form of hypobetalipoproteinemia and may be caused by a defect in the final assembly of chylomicrons or in the mechanism of their exocytosis.
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PMID:Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B. Chylomicron retention disease. 379 76

Rare instances of symptomatic fat malabsorption have been reported in patients with heterozygous hypobetalipoproteinemia, but with an unclear pathogenesis. An 8-month-old boy with chronic diarrhea and failure to thrive was found to have abnormally low plasma total cholesterol (85 mg/dl), LDL-cholesterol (48 mg/dl), apoB (52 mg/dl), apoA-I (53 mg/dl), and vitamin E (0.22 mg/dl). Decreased plasma LDL-C and apoB were noted in the father (34 and 40 mg/dl, respectively), as well as several other family members. Fasting triglycerides were normal but did not increase normally in response to a fat meal test. Lipoprotein composition showed an abnormal profile of very low density (VLDL, d 1.006 g/ml), low density (LDL, d 1.063 g/ml), and high density (HDL, d 1.21 g/ml) lipoproteins. A fasting jejunal biopsy revealed lipid-laden enterocytes. Electron microscopy of the jejunal biopsy revealed the absence of lipid particles in the intercellular spaces after a fat meal. Jejunal explants cultured with [14C]palmitate and [3H]leucine showed limited synthesis of triglycerides and apolipoproteins (36 and 42% of controls, respectively), whereas the father's results were close to normal. At 1 year of age, improvement in intestinal fat absorption was accompanied by the presence of chylomicrons in the intercellular space, concomitant with the enhanced synthesis of lipids and apoB by jejunal explants. These data provide evidence that heterozygous hypobetalipoproteinemia may present early in life as transient, symptomatic lipid malabsorption. The mechanisms responsible for improved lipid transport despite persistent hypobetalipoproteinemia remain to be established.
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PMID:Variable expression of familial heterozygous hypobetalipoproteinemia: transient malabsorption during infancy. 789 15

The fifth- and ninety-fifth-percentile concentrations of low-density lipoprotein (LDL) cholesterol in most Western populations are approximately 90 and 200 mg/dl, respectively. Persons with LDL cholesterol levels equal to or less than the fifth percentile are defined as having hypobetalipoproteinemia. Epidemiologic studies show that such individuals have lower-than-average risk for atherosclerotic cardiovascular disease but higher risk for a variety of cancers, pulmonary, and gastrointestinal diseases than persons with higher levels of cholesterol. The reasons for this are not known, nor are the causes of most cases of hypobetalipoproteinemia. However, in some well-studied kindreds the hypobetalipoproteinemia phenotype is inherited as an autosomal dominant trait. Heterozygotes in such kindreds are usually healthy and have no difficulty absorbing dietary fat. In most kindreds, the molecular variants responsible for the hypobetalipoproteinemia are unknown, but a subset of kindreds have strong genetic linkages between the low-cholesterol phenotype and truncation-producing mutations of the apolipoprotein (apo) B-100 gene. The truncations of apoB are named according to a centile nomenclature. The full-length 4536-amino acid protein is called apoB-100, and the 25 truncations identified to date have been named apoB-2 to apoB-89. The mutations introduce premature termination codons resulting from frameshift-producing base additions or deletions. The mutations produce slowed rates of secretion of the truncated apoBs relative to the apoB-100s present in the heterozygotes. In addition, the apoB-100 molecules of the heterozygotes are also secreted at rates slower than those observed in closely matched normolipidemic controls. These physiologic results account for the hypobetalipoproteinemia of these subjects. The response of the plasma lipoproteins of heterozygotes to the manipulation of various dietary components remains to be determined. Additional low-cholesterol syndromes are autosomal recessive forms of hypobetalipoproteinemia, chylomicron retention disease, and abetalipoproteinemia. The molecular causes of the first two are unknown. Abetalipoproteinemia is an autosomal recessive condition resulting from mutations of the microsomal triglyceride transfer protein. All three conditions are characterized by vanishingly small concentrations of LDL, dietary fat malabsorption, and failure to thrive in infancy.
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PMID:The hypobetalipoproteinemias. 852 19

For decades, research interest has focused on hypertriglyceridemia and hypercholesterolemia, because of their association with atherosclerosis. Recently, however, increasing attention has been paid to rare hypolipidemic states that can cause adverse consequences in young patients. Studies of genetic disorders of fat transport have afforded new insights into the mechanisms involved in intestinal lipid handling and lipoprotein metabolism. This article reviews briefly the current state of knowledge about inherited lipoprotein deficiencies, including abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease. These disorders share many common characteristics: they all cause fat malabsorption, low levels of circulating lipids and fat-soluble vitamins, failure to thrive in early childhood, ataxic neuropathy and visual impairment. However, their etiology is genetically different. Abetalipoproteinemia is caused by the absence of microsomal transfer protein, whereas hypobetalipoproteinemia is due to defects in the apolipoprotein B gene. The etiopathogenesis of chylomicron retention disease is as yet unexplained. Research on these rare, inherited fat disorders of absorption will continue to provide significant advances in our understanding of human physiology and may yield novel therapeutic approaches to atherosclerosis.
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PMID:The genetic basis of primary disorders of intestinal fat transport. 888 69


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