Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case report is presented of a young woman in whom symptomatic porphyria cutanea tarda (PCT) developed during copper chelation therapy for Wilson's disease. The 22 year old white woman was seen in the summer of 1978 because of development of blisters on the dorsa of the hands associated with focal atrophic hypopigmentation, generalized hyperpigmentation of the skin, and hpertrichosis of the lateral forehead and face. A sibling had died in childhood with Wilson's disease. When the patient developed hepatomegaly, ascites, and an acute hepatitis syndrome at the age of 11, penicillamine therapy was empirically started, with gradual symptomatic improvement. When evaluated at the age of 22, abnormal laboratory values included a total bilirubin of 1.2 mg%; alkaline phosphatase, 96 U; serum glutamic oxaloacetic transaminase (SGOT), 175 U; serum glutamic pyruvic transaminase (SGPT), 122 U; gamma glutamyl trans peptidase (GGTP), 64 U; and Bromsulphalein (BSP) retention, 21% at 45 minutes. Skin biopsy from the hand revealed a noninflammatory subepidermal bulla with prominently PAS positive vessel walls in the festooned dermal papillae at the base of the blister. A fragmented liver biopsy failed to reveal evidence of active hepatitis or cirrhosis, but considerable stainable iron was present in both hepatocytes and Kupffer cells. A rubeanic acid stain for copper was negative. The patient was diagnosed as having Wilson's disease, hepatic hemosiderosis, and PCT. Cessation of all ethanol consumption and discontinuation of the oral contraceptives which she had been taking for 6 years, was recommended. On examination 9 and 22 months after these modifications were instituted, the patient felt asymptomatic and was without evidence of any new blisters or scars of her skin. The hyperpigmentation and hypertrichosis persisted, but she rigidly adhered to a program of penicillamine, topical sunscreen application, and abnegation of alcohol. Liver function studies were normal, and urinary porphyrin levels returned toward normal values. The clinical onset of this patient's blistering disease was temporally associated with ethanol and exogenous estrogen medication.
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PMID:Porphyria cutanea tarda complicating Wilson's disease. 720 91

The effect of histidine-supplemented stock diets on plasma cholesterol and on the amelioration of the hypercholesterolemia by simultaneous copper supplementation was examined in rats. Weanling male Sprague-Dawley rats, five groups of 10 animals each, were fed ground stock diets unsupplemented or supplemented with 8% L-histidine, 8% L-histidine plus 222.8 micrograms Zn/g and 8% L-histidine plus 56.6 micrograms Cu/g. On day 46 plasma and liver cholesterol, copper and zinc concentrations were determined by colorimetry and atomic absorption spectrophotometry. Histidine supplementation produced hepatomegaly, depressed growth, a 131.8% (P less than 0.001) increase in plasma cholesterol and significant reductions in plasma copper and zinc and liver copper concentrations. The simultaneous feeding of histidine and zinc-supplemented stock diet failed to alter the hypercholesterolemia despite elevation in plasma zinc to values in excess of control animals. The simultaneous feeding of histidine and copper-supplemented stock diets abolished the hypercholesterolemia, reduced the hepatomegaly observed with histidine alone and elevated tissue copper concentrations to values in excess of control animals. Tissue copper and cholesterol concentrations showed significant negative correlations. No correlations between zinc and cholesterol were observed. The results suggest that histidine-induced hypercholesterolemia is due to changes in copper status, and is abolished by simultaneous copper supplementation.
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PMID:Dietary L-histidine-induced hypercholesterolemia and hypocupremia in the rat. 721 37

Unexplained fractures are characteristic of both osteogenesis imperfecta (OI) and non-accidental injury (NAI) but in most cases the diagnosis is straightforward. However, in a few OI patients an initial diagnosis of NAI is made. Factors contributing to such difficulties include failure to recognise that OI can occur without a family history, without blue sclerae, without osteopenia, without an excess of Wormian bones, or with metaphyseal fractures. In addition we report on 39 patients with an unusual history in that fractures only occurred in the first year of life. Rib fractures, metaphyseal abnormalities and periosteal reactions were common. The initial diagnosis was usually OI if the fractures occurred in hospital, but NAI if they appeared to have been sustained at home. Additional findings such as anaemia, vomiting, hepatomegaly, and apnoeic attacks were often found in these patients. The disorder has some similarities to the syndrome of infantile copper deficiency. Like the latter it is particularly common in preterm infants and in twins. Therefore, we are attempting to examine the incidence of significant hypocupraemia in unselected preterm infants. We suggest that the likely cause of this "temporary brittle bone disease" is a temporary deficiency of an enzyme, perhaps a metalloenzyme, involved in the post-translational processing of collagen.
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PMID:Osteogenesis imperfecta: the distinction from child abuse and the recognition of a variant form. 817 41

Primary hemochromatosis is characterized by a specific pattern of clinical manifestations. It includes liver disease with hepatomegaly, glucose intolerance, e.g. diabetes, hyperpigmentation oft the skin, impotence/ amenorrhea, arthropathy, cardiomyopathy and fatigue. Laboratory investigation reveals significantly elevated serum ferritin and transferrin saturation with iron. The diagnosis is confirmed by liver biopsy and quantitative determination of elevated liver iron content. Wilson's disease represents a copper storage disease. Prominent clinical features are hepatomegaly and splenomegaly. Neurological alterations and detection of Kayser-Fleischer corneal rings are typical. In the acute initial phase the often young patients present with Coombs-negative hemolysis. Psychiatric alterations, cardiomyopathy, arthropathy, nephropathy, as well as thrombocytopenia and leucopenia are other clinical features. Laboratory parameters of Wilson's disease include low serum ceruloplasmin and serum copper. There is an elevated urinary copper excretion and elevated serum free copper concentration. The diagnosis is confirmed by liver biopsy with quantitative determination of an elevated liver copper content.
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PMID:[Current diagnosis: hereditary metabolic diseases of the liver (primary hemochromatosis, Wilson disease)]. 898 78

Brazil has a young population and areas of endemic mansoni schistosomiasis where Wilson's disease might be easily misdiagnosed in patients erroneously classified as having either the hepatosplenic or the hepatointestinal form of the helminthiasis. Twenty five patients with the "hepatic form" of Wilson's disease (14 males and 11 females) were investigated in Belo Horizonte, MG; the mean age was 13.7 years (3 to 22). Nineteen had hepatomegaly (76%) and nine splenomegaly (36%). Twenty two (88%) had cirrhosis. The Kaiser-Fleisher ring was detected in fifteen (60%). Four (16%) had clear neurological abnormalities. Eleven (44%) had ascitis and/or jaundice. Ninety one point three per cent and 92% had low ceruloplasmin and copper serum levels respectively. Eighty four point two per cent showed an increased 24 hours urinary copper excretion; seven patients in whom hepatic copper was determined had increased values. Six out of nine had at least a ten fold increase in 24 hours urinary copper excretion following penicillamine use ("penicillamine test"). Three out of 19 patients (15.8%) had mansoni schistosoma ova in stools examination, a common prevalence in our population. Their biopsies showed inactive cirrhosis without schistosomiasis-associated alterations. At least fourteen patients (56%) could be misdiagnosed as having hepatointestinal or hepatosplenic schistosomisis when in fact they suffered from Wilson's disease with or without asymptomatic intestinal schistosomiasis, losing the chance of an early treatment. The follow-up time of 22 patients was 52 months (1 to 96); eight (36.3%) died, four from bleeding esphageal varices, three from terminal hepatic failure and one from fulminant liver failure. The majority of the patients, including those who died, had abandomned the use of penicillamine or had taken it irregularly, due mainly to its highly expensive cost. A 17 year old patient underwent a successful liver transplant in 1989.
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PMID:[Wilson's disease ("hepatic form") in a region endemic for schistosomiasis mansoni: clinical presentation of 25 patients]. 971 8

Veal calf producers in Indiana have reported condemnation of carcasses due to icterus as well as condemnation of livers because of yellow discoloration, hepatomegaly and fibrosis. This study assessed the degree of hepatic injury in affected veal calves and correlated it with copper, iron and zinc concentrations in the liver and kidney. Tissues examined histopathologically were from slaughtered and necropsied veal calves. Hepatic lesions were divided into histopathologic categories of severity (minimal, moderate, marked or severe) based upon the degree of fibrosis, biliary epithelial hyperplasia, and inflammation. Hepatic copper levels decreased as the severity of lesions increased. The clinical observations and morphologic changes suggested initial hepatic damage before 9 w-of-age. The affected calves either died of acute copper toxicosis or survived to develop hepatomegaly, hepatic discoloration and/or fibrosis at the time of slaughter.
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PMID:Comparison of hepatic lesions in veal calves with concentrations of copper, iron and zinc in liver and kidney. 1034 10

Mutations in the Wilson disease gene ATP7B, a P-type ATPase, are responsible for copper accumulation in the liver and other organs leading to Wilson disease (WD, OMIM 277900). Clinical manifestations of Wilson disease (WD) include chronic liver disease, acute hepatic failure or neuropsychiatric diseases. Since potent medical treatments are available to prevent disabling residual symptoms, early diagnosis is crucial. To demonstrate the clinical course and genetic findings, a male patient with a novel mutation in the ATP7B gene, a 10 base pair insertion in exon 6 (1927ins 10), and a second missense mutation in exon 13 (P992L) is reported. The patient presented with signs of chronic liver disease at the age of 10 years. Clinical findings included hepatomegaly, elevated liver enzymes and coagulopathy. A combination treatment with the copper chelating agent D-penicillamine and zinc acetate was started leading to normalization of liver function and no appearance of neurological signs or Kayser-Fleischer ring after 7 years follow-up. Truncating mutations of the ATP7B gene (insertions, deletions, nonsense mutations) leading to gross loss of C-terminal parts of the protein, thereby probably completely destroying the protein function, may correlate with a hepatic phenotype and early onset as seen in the patient presented.
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PMID:Disturbed copper transport in humans. Part 2: mutations of the ATP7B gene lead to Wilson disease (WD). 1193 61

Acute hepatic failure has been reported in the presence of Epstein-Barr virus (EBV) infection. Autoimmune hemolytic anemia may also occur in the course of this infection. We report a rare case of fulminant hepatic failure and autoimmune hemolytic anemia associated with Epstein-Barr virus. A seven-year-old girl was admitted with the complaints of abdominal pain, vomiting and jaundice. She was irritable, confused and had mild hepatomegaly with marked splenomegaly. Serum aminotransferase levels were moderately elevated, while direct and indirect bilirubin levels were markedly elevated. Prothrombin time was prolonged. Hemoglobin was 3.9 g/dl. Anti-HAV IgM, HbsAg, anti-HBc IgM, anti-HCV and anti-CMV IgM were negative, while IgM VCA EBV, IgG VCA EBV and anti-CMV IgG were positive. Serum copper and ceruloplasmin levels were normal. The patient received supportive therapy for hepatic failure. Meanwhile, the cause of the deep anemia was investigated and autoimmune hemolytic anemia was ascertained by means of increased reticulocyte count and positive Coombs test. Corticosteroid therapy was administered. The prognosis was good. Although not reported before, the combination of acute hepatic failure and autoimmune hemolytic anemia may complicate the course of EBV infection. Physicians need to be aware of this association.
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PMID:Fulminant hepatic failure and autoimmune hemolytic anemia associated with Epstein-Barr virus infection. 1221 11

In order to investigate whether cholesterol intake influences the hepatic copper content of rabbits, we compared the hepatic copper content of two rabbit inbred strains after feeding the animals a control or a cholesterol-rich diet. One strain was not reactive to dietary cholesterol (IIIVO/JU), whereas the other strain was reactive to dietary cholesterol (AX/JU). The coefficient of inbreeding (F) >0.95 for both strains. Dietary cholesterol-reactive rabbits when compared with their non-reactive counterparts had a higher hepatic copper content. The consumption of a hypercholesterolemic diet decreased liver copper concentration (expressed in micro g/g dry weight) in both strains of rabbits, which was (in part) due to dietary-induced hepatomegaly. A decrease in the absolute hepatic copper content was found only in the dietary cholesterol-reactive inbred strain. It is discussed that differences in glucocorticoid levels may be responsible for the strain difference in liver copper content. The cholesterol effect on the hepatic copper content in the reactive strain might be caused by an increased bilirubin secretion.
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PMID:Cholesterol and copper in the liver of rabbit inbred strains with differences in dietary cholesterol response. 1294 76

The question addressed is whether cholesterol intake reduces the hepatic copper content in rats. For this purpose we have compared the hepatic copper content of two selected rat inbred strains after feeding the animals a control or a high fat, high cholesterol diet. One strain was dietary cholesterol resistant (SHR/OlaIpcv), whereas the other strain was susceptible to dietary cholesterol (BN-Lx/Cub). Dietary cholesterol-susceptible rats have a lower baseline hepatic copper content when compared with their resistant counterparts. The consumption of a hypercholesterolemic diet decreased the liver copper concentration (expressed in microg/g dry weight) to about the same extent in both strains. However, dietary cholesterol did not reduce the absolute (expressed as microg/whole liver) and relative (expressed as microg/whole liver/100 g body weight) copper store of rats. The decrease of liver copper concentration after the high fat, high cholesterol diet is probably not caused by a decrease in whole hepatic copper content, but rather due to dietary-induced hepatomegaly.
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PMID:Liver copper content of rats hypo- or hyperresponsive to dietary cholesterol. 1496 30


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