1/8. A study of fatty liver disease and plasma lipoproteins in a kindred with familial hypobetalipoproteinemia due to a novel truncated form of apolipoprotein B (APO B-54.5).BACKGROUND/AIMS: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by reduced plasma levels of low-density lipoproteins. It can be caused by mutations in the gene encoding apolipoprotein b-100 (apo B), leading to the formation of truncated apo Bs which have a reduced capacity to export lipids from the hepatocytes as lipoprotein constituents. case reports suggest the occurrence of liver disease in FHBL, but there are no studies of liver involvement in FHBL with defined apo B gene mutations. The presence of fatty liver disease was investigated in a large FHBL kindred. methods: plasma lipoprotein and apolipoprotein analysis, liver function tests, and apo B gene sequence were performed in 16 members of a FHBL kindred. The presence of fatty liver was assessed by ultrasound and computed tomography scanning. RESULTS: The proband, a non-obese heavy drinker male with hypobetalipoproteinemia, had steatohepatitis with fibrosis. He was heterozygous for a novel non-sense mutation of apo B gene producing a truncated apo B of 2745 amino acids (designated apo B-54.5, having half the size of normal apo B-100). Seven other members of his kindred carried apo B-54.5. Although all of them were hypolipidemic, their lipid levels showed a large inter-individual variability not accounted for by polymorphisms of genes involved in apo B metabolism. Four carriers (two heavy drinkers and two teetotallers), irrespective of their plasma lipid levels, had ultrasonographic evidence of fatty liver. In the other four carriers no evidence of fatty liver was found. CONCLUSIONS: In this kindred apo B-54.5 predisposes to fatty liver, which however may require some additional factors to become clinically relevant.- - - - - - - - - - ranking = 1keywords = fatty liver, fatty (Clic here for more details about this article) |
2/8. Liver dysfunction and steatosis in familial hypobetalipoproteinemia.A 32-year-old man presented with increases in serum alanine aminotransferase activity, iron concentration, and transferrin saturation, suggestive of hepatic dysfunction and iron overload. In addition, he had unusually low plasma concentrations of LDL-cholesterol and apolipoprotein (apo) B. Hepatic ultrasonography was consistent with fatty liver. On liver biopsy, marked steatosis and moderate to marked iron deposition were observed. The patient was found to carry the HFE C282Y and H63D mutations, which are associated with hereditary hemochromatosis, and the alpha(1)-antitrypsin PiZ variant. An immunoblot of plasma for apoB showed the presence of a truncated apoB species, indicative of familial hypobetalipoproteinemia. dna sequence analysis revealed that the patient was heterozygous for the apoB-80.5 (c.11040T>G) mutation. This unique case shows an unusual combination of underlying disorders that could all be contributing to liver dysfunction and fatty liver.- - - - - - - - - - ranking = 0.22222222222222keywords = fatty liver, fatty (Clic here for more details about this article) |
3/8. Pediatric gallstone disease in familial hypobetalipoproteinemia.Familial hypobetalipoproteinemia (FHBL) is an monogenic co-dominant disorder characterized by reduced plasma levels of cholesterol, low density lipoproteins (LDL) and apolipoprotein B (apoB) often associated with non-alcoholic fatty liver disease (NAFLD). It has been suggested that FHBL might predispose to gallstone disease (GD). We report a hypocholesterolemic 10 year old girl with obstructive jaundice due to cholesterol stones in gallbladder and common bile duct which required cholecistectomy. The analysis of patient's plasma lipoproteins revealed a marked reduction of LDL and apoB, a lipid profile consistent with the clinical diagnosis of heterozygous FHBL. The same profile was found in her mother who had severe NAFLD. The analysis of apoB gene, the main candidate gene in FHBL, revealed that the patient and her mother were heterozygotes for a novel nonsense mutation (Y1220X) predicted to cause the formation of a short truncated apoB (apoB-26.87) not secreted into the plasma. The presence of cholesterol stones could result from increased biliary cholesterol secretion as a compensatory mechanism for the reduced capacity of the liver to export cholesterol incorporated into apoB-containing lipoproteins. FHBL should be considered as a possible predisposing factor for cholesterol gallstones in children (190).- - - - - - - - - - ranking = 0.11111111111111keywords = fatty liver, fatty (Clic here for more details about this article) |
4/8. Lipid composition and lipolytic activities in milk from a patient with homozygous familial hypobetalipoproteinemia.We have investigated the composition of breast milk from a patient with abetalipoproteinemia. Activity level and specific activity of lipoprotein lipase in milk samples obtained at 0.5 and 3 mo postpartum were higher than those found in normal milk; activity of bile salt-activated lipase was found to be higher in the milk at 6 mo postpartum than in normal milk but average specific activity of this enzyme in milk samples was not increased. Except for higher protein content of patient's milk, there was no apparent abnormality in the protein pattern as determined by SDS-polyacrylamide gel electrophoresis. Lipid analysis indicated a shift in the molecular weight distribution of triglycerides, which favored lower molecular weight forms and reflected an increase in medium-chain and a major decrease in long-chain essential fatty acids (omega 6 and omega 3) in milk triglycerides.- - - - - - - - - - ranking = 0.0007680924036693keywords = fatty (Clic here for more details about this article) |
5/8. fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B.fatty liver has been anecdotally associated with heterozygous hypobetalipoproteinemia. The aim of this study was to characterize the molecular defect in a subject with heterozygous hypobetalipoproteinemia (low-density lipoprotein cholesterol, 52 mg/dL; apolipoprotein [apo] B, 15 mg/dL) and otherwise unexplained fatty liver. plasma lipoproteins were separated by ultracentrifugation, and apo B was analyzed by electrophoresis and immunoblotting. A fragment of genomic dna corresponding to the 5' end of exon 26 of the apo B gene was amplified by polymerase chain reaction and sequenced. The plasma lipoproteins of the proband contained, besides normal apo B-100, a 200-kilodalton truncated apo B whose size suggested the presence of a mutation in exon 26 of the apo B gene. The nucleotide sequence of a fragment of the 5' end of exon 26 revealed that the proband was a heterozygote for a 14-nucleotide deletion, producing a frameshift resulting in a premature stop codon at residue 1768. This truncated apo B was named apo B-38.95. The proband's father was a carrier of the same mutation. fatty liver in this subject with familial heterozygous hypobetalipoproteinemia most likely results from the inability of apo B-38.95 to export lipids from hepatocytes into the blood stream. Heterozygous hypobetalipoproteinemia should be considered in a hypolipidemic subject with an otherwise unexplained fatty liver.- - - - - - - - - - ranking = 0.22222222222222keywords = fatty liver, fatty (Clic here for more details about this article) |
6/8. fatty liver in a case with heterozygous familial hypobetalipoproteinemia.We herein present a case of fatty liver in a patient with heterozygous familial hypobetalipoproteinemia. A 34-yr-old male presented with abnormally elevated levels of transaminases and a fatty liver. He was asymptomatic, and the physical examination showed nothing remarkable. The serum total cholesterol, triglyceride, LDL-cholesterol, and apolipoprotein B levels all ranged from low normal to one-half normal. His other laboratory data were all in the normal range. The patient's body mass index measured was 25.7 kg/m2, and he did not demonstrate obesity. He had no history of alcohol consumption. It was thus thought that the fatty liver in this case might be associated with heterozygous hypobetalipoproteinemia. Heterozygous hypobetalipoproteinemia with a bright liver by ultrasound was also found in several of the patient's family members. Based on these rare findings, heterozygous hypobetalipoproteinemia should thus be considered as a possible cause in patients presenting with an unexplained fatty liver.- - - - - - - - - - ranking = 0.44444444444444keywords = fatty liver, fatty (Clic here for more details about this article) |
7/8. Persistent transaminase elevation due to heterozygous (familial) apolipoprotein B deficiency.Homozygous apolipoprotein B deficiency can present with fatty liver and raised levels of transaminases. Subjects with heterozygous deficiency are almost always asymptomatic. We report an asymptomatic 26-year-old man with persistently raised transaminases, in whom the diagnosis of heterozygous (familial) apolipoprotein B deficiency was made on the basis of characteristic lipid profile.- - - - - - - - - - ranking = 0.11111111111111keywords = fatty liver, fatty (Clic here for more details about this article) |
8/8. Diffuse fatty liver in familial heterozygous hypobetalipoproteinemia.A 34-year-old man had asymptomatic hepatomegaly, slightly increased serum alanine aminotransferase and gamma-glutamyl transpeptidase levels, and a sonographic pattern suggesting diffuse hepatic steatosis. Liver biopsy revealed fatty change in 25% to 50% of hepatocytes. The patient also had low serum levels of cholesterol and triglycerides and met clinical, biochemical, and familial diagnostic criteria of heterozygous hypobetalipoproteinemia. We could not relate his hepatic steatosis to any already known cause of fatty liver and could only attribute it to heterozygous hypobetalipoproteinemia. Familial heterozygous hypobetalipoproteinemia should be ruled out in patients with unexplained hepatic steatosis.- - - - - - - - - - ranking = 0.55632364795922keywords = fatty liver, fatty (Clic here for more details about this article) |