Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty five cases of chronic pancreatitis have been diagnosed between January 1966 to July 1983 in the Hospital A. Posadas. The diagnosis was confirmed by the presence of one or more of the following data: pancreatic calcifications positive in 35, abnormal secretin test 37, ultrasonography and computed tomography pathological findings 10. Surgical operations were carried out in 25 patients and biopsy taken in 5. Thirty nine (86.6%) were males, 6 (13.3%) females, the mean age in each group was 47.4 and 39.8 years. Chronic alcoholism was certain in 41 (91.9) patients, in the remainder 4 no other etiologic factors were found. The main clinical data were: Weight loss 38 (84.4%) diabetes 34 (75.5%) pain 33 (73.3% in 7 as acute pancreatitis) Steatorrhea 23 (51.1%) jaundice 16 (35.5%- 11 by extrahepatic biliary tree obstruction, 5 by hepatic cirrhosis) pseudocysts 12 (26.6%). The more common associated diseases were: hepatic cirrhosis 6, fatty liver 2 (17.7%) gastroduodenal ulcer 6 (13.3%) cancer 4 (8.8%--gastric 1, pancreatic 3). In order to study the frequency of the clinical data the patients were grouped according to the presence or absence of calcifications and the etiologic factor Symptoms and signs were matched and statistic analysis (coefficient association phi) was made. Only a moderate association between acute pancreatitis in no calcified group and diabetes in calcified group were found. The chronologic study of certains clinical data shows that acute pancreatitis, jaundice, pseudo-cyst and surgical operations were significative more frequent in the first five years while diabetes has little more frequency in the second five year period. Twenty six surgical operations were carried out in 25 patients; 20 (76.9%) due to complications, 6 (23.1%) secondary to pain (pancreatic resection 3, pancreatoyeyunostomy 2, exploration 1). Twenty three patients were lost to follow-up, 12 died and 10 are still alive. This last group was followed at regular period, 8 remained asymptomatic and 2 have intermittent abdominal pain related to alcoholic ingestion.
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PMID:[Chronic calcified pancreatitis. Our experience]. 639 6

We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L. kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous for a T-deletion in exon 26, which converts tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an apoB-75.7 carrier, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.
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PMID:Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene. 1159 Feb 10

Homozygous familial hypobetalipoproteinaemia (Ho-FHBL) is a rare co-dominant disorder characterized by extremely low levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). Most patients with Ho-FHBL have mutations in APOB gene resulting in truncated apoBs. Some patients are asymptomatic, while others have fatty liver, intestinal fat malabsorption and neurological dysfunctions. We investigated three adult subjects with severe hypobetalipoproteinaemia and a family history of FHBL. Proband FHBL-47 had liver cirrhosis with hepatocarcinoma and a renal carcinoma but no clinical manifestations related to FHBL. He was a compound heterozygote for a 7-bp deletion in exon 21 and a base insertion in exon 26 resulting in truncated apoBs (apoB-22.46/apoB-66.51). Proband FHBL-53, with severe hepatic steatosis and fibrosis, had a nonsense mutation in exon 19 resulting in a truncated apoB (apoB-20.61) and a rare nucleotide substitution in intron 14 (c.2068-4T>A). The latter was also present in her daughter, found to have low plasma LDL-C and apoB. Proband FHBL-82 had chronic diarrhoea and steatorrhoea. She was found to be homozygous for a nonsense mutation in exon 24 resulting in a truncated apoB (apoB-26.65). In adult subjects, the presence of chronic liver disease and chronic diarrhoea, when associated with severe hypobetalipoproteinaemia, may lead to the diagnosis of Ho-FHBL.
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PMID:Variable phenotypic expression of homozygous familial hypobetalipoproteinaemia due to novel APOB gene mutations. 1849 86

Current lipid-lowering drugs are often unable to achieve low density lipoprotein cholesterol (LDL-C) goals. Moreover, despite LDL-C lowering mostly by statins, a considerable residual vascular risk remains. This is partly associated with atherogenic dyslipidemia where apolipoprotein (apo) B-containing lipoproteins predominate. Mitochondrial Triglyceride (TG) transfer protein (MTP) is a key enzyme for apoB-containing lipoprotein assembly and secretion. This is mostly attributed to its capacity to transfer lipid components (TGs, cholesterol esters and phospholipids) to the endoplasmic reticulum lumen, where these lipoproteins are assembled. Several agents were developed to inhibit MTP wherever it is expressed, namely the liver and/or the intestine. Liver-specific MTP inhibitors reduce secretion of very low density lipoproteins (VLDL) mostly containing apoB100, while the intestine-specific ones reduce secretion of chylomicrons containing apoB48. These drugs can significantly reduce total cholesterol, LDL-C, TGs, VLDL cholesterol, as well as apoB levels in vivo. They may also exert anti-atherosclerotic and insulin-sensitizing effects. Limited clinical data suggest that these compounds can also improve the serum lipid profile in patients with homozygous familial hypercholesterolemia (HoFH). The accumulation of unsecreted fat in the liver and intestinal lumen is associated with elevation of aminotransferases and steatorrhea. Liver steatosis can be avoided by the use of intestine-specific MTP inhibitors, while steatorrhea by low-fat diet. Future indications for these developing drugs may include dyslipidemia associated with insulin resistant states, familial combined hyperlipidemia and HoFH. Future clinical trials are warranted to assess the efficacy and safety of MTP inhibitors in various clinical states.
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PMID:Mitochondrial triglyceride transfer protein inhibition: new achievements in the treatment of dyslipidemias. 2331 3

Extremely low LDL-cholesterol concentrations are very unusual and generally related with comorbidities accompanying malnutrition. Less frequently low LDL-cholesterol levels result from mutations in the APOB, PCSK9, ANGPTL3, SAR1B and MTTP genes (primary hypobetalipoproteinemia). We investigated three patients with plasma LDL-cholesterol levels below the fifth percentile of the Spanish population. We recorded data on demographic and anthropometric characteristics, life style habits, physical examination, liver ultrasound and lipid and lipoprotein levels, in the probands and their first-degree relatives. Secondary causes of hypocholesterolemia were ruled out by clinical study, complementary tests and follow-up. The APOB, MTTP and SAR1B genes were sequenced. Patients were found to be heterozygotes for point mutations located in the exon 26 of the APOB gene. One patient, with fatty liver, carried a previously described mutation (c.7600C>T) (Arg2507X), causing the formation of truncated Apo B-55.25. The other two mutations producing truncations are new. One asymptomatic patient carried the Arg3672X (Apo B-80.93) and the other with fatty liver and steatorrhea carried the Ser2184fsVal2193X (Apo B-48.32). Our study reinforces the concept that in the heterozygous carriers of truncated Apo Bs, the clinical manifestations of FHBL are dependent on the size of the truncations.
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PMID:Familial hypobetalipoproteinemia: analysis of three Spanish cases with two new mutations in the APOB gene. 2400 80

Abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL) are genetic diseases characterized by low density lipoprotein deficiency. ABL presents early in life with the gastroenterological manifestations of fat malabsorption, steatorrhea, and failure to thrive, and later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E. Heterozygous FHBL subjects are usually asymptomatic, but may develop fatty liver disease. In homozygous (compound heterozygous) FHBL, the clinical and biochemical features are indistinguishable from those of ABL and treatment recommendations are the same: dietary fat restriction to prevent steatorrhea, and long-term high-dose vitamin E and A supplementation to prevent or at least slow the progression of neuromuscular and retinal degenerative disease. Despite their low plasma vitamin E levels, individuals with heterozygous FHBL do not require vitamin E supplementation. There are conflicting reports on whether increased oxidative stress is seen in ABL; these differences may relate to the small size of patient groups as well as differences in patient age and dose of vitamin E supplementation, or the contribution from dietary sources of vitamin E. High density lipoproteins in ABL appear to be severely oxidized yet able to inhibit platelet aggregation by binding to scavenger receptor B1. We review the role of vitamin E and oxidative stress in ABL and FHBL.
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PMID:Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia. 2608 16