Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-1-antitrypsin deficiency is an inborn metabolism error which can cause emphysema and liver disease. As regards the pathophysiology of liver disease, this deficiency is poorly understood, and it is also not known why only a small proportion of Pi ZZ individuals progress towards cirrhosis and liver failure. Since there is no specific therapy for end-stage liver disease associated with alpha-1-antitrypsin deficiency, patients are considered candidates for liver transplantation. In this paper, the natural history of 16 children who underwent liver transplantation is reviewed. Fourteen patients had neonatal cholestasis as a first symptom of the disease and hepatosplenomegaly was present in all children by the age of 12 months. In 11 children, jaundice recurred, always with liver function deterioration. Two patients had a histological paucity of interlobular bile ducts and required early transplantation due to rapid progression of liver failure. At the time of pretransplant assessment, all the patients in this study had portal hypertension and seven of them had experienced at least one episode of gastrointestinal bleeding. One child had moderate intrapulmonary shunts with hypoxemia, but the others had normal spirometry and blood gases. There was no other extrahepatic complication of alpha-1-antitrypsin deficiency. Eighteen orthotopic liver transplantations were performed in 16 patients. One patient died 8 days after retransplantation due to graft necrosis. Fifteen patients (94%) were alive after a median follow-up of 22 months with an excellent quality of life, normal serum alpha-1-antitrypsin levels and without evidence of liver disease recurrence or pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver transplantation for end-stage liver disease associated with alpha-1-antitrypsin deficiency in children: pretransplant natural history, timing and results of transplantation. 820 Dec 25

BALB/c mice injected at birth with (BALB/c x C57BL/6)F1 hybrid spleen cells developed host versus graft disease (HVGD) with immunological features, such as various autoantibodies, immune complex nephritis, hepatosplenomegaly, and malignant lymphomas. In addition we found that the increased IgE levels correlated strongly with the histological grades or stages of the liver disease. In the sera of mice with HVGD and liver alterations, anti-smooth muscle antibodies (ASMA) and anti-nuclear antibodies (ANA) were detected. The subclass of ASMA was IgG1, whereas the subclasses of ANA were IgG1, IgG2a, and IgG2b. When the recipient BALB/c mice were injected at birth and at Day 3 in addition also with monoclonal anti-IL-4 antibody 11B11, the increase of IgE and IgG1 was markedly reduced and the liver disease was drastically prevented. These observations suggest that IL-4 plays an important role in the initiation of the immunoregulatory function or pathogenesis of the allogeneic effects and that the monoclonal anti-IL-4 antibody 11B11 prevents the immunodysfunctions and the autoimmune hepatopathy in mice with HVGD. The increased IgE level in the serum is a good marker of HVGD.
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PMID:Increased IgE level as a marker of host-versus-graft disease: inhibition of this HVGD with a monoclonal antibody to IL-4. 851 6

Indian childhood cirrhosis (ICC) is an almost uniformly fatal disease whose outcome may be modified with penicillamine if given at a sufficiently early stage. Twenty nine children with ICC seen in Pune, India, in 1980-7, who had survived at least five years from onset of penicillamine treatment, were reviewed aged 6.3 to 13 years. They were assessed clinically, biochemically, histologically, and by duplex Doppler ultrasound examination. None had symptoms suggestive of liver disease. There were no toxic effects of penicillamine other than asymptomatic proteinuria. Hepatosplenomegaly reduced significantly and liver function tests returned to normal in all. In four children, significant hepatosplenomegaly was associated with an abnormal duplex Doppler hepatic vein flow pattern and micronodular cirrhosis on biopsy. Clinical findings, growth and development, and ultrasound examination were normal in the remainder. Review of serial liver biopsy specimens showed a sequence of recovery from ICC through inactive micronodular cirrhosis to virtually normal histological appearances. The four children who still have micronodular cirrhosis beyond four years from onset remain on penicillamine treatment. In the others penicillamine was stopped after 1-7 (mean 3.5) years without relapse, strong evidence that ICC is not due to an inborn error of copper metabolism.
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PMID:Long term survival in Indian childhood cirrhosis treated with D-penicillamine. 866 42

Type IV glycogenosis is usually a rapidly progressive disease of early childhood, causing death before 4 years of age. It is characterized by hepatosplenomegaly, cirrhosis, and chronic hepatic failure. Muscle involvement is generally overshadowed by liver disease. A mild non-infantile variant of type IV glycogenosis has been described in a few patients. In some of them, the patients suffered foremost from chronic progressive myopathy. We here report on a female patient aged 51 years who had experienced difficulties in climbing stairs for 2 years due to leg weakness. EMG revealed a myopathic pattern. The muscle biopsy findings revealed polyglycosan bodies. Biochemical investigation showed absence of branching enzyme in muscle but not in leukocytes and fibroblasts.
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PMID:A mild adult myopathic variant of type IV glycogenosis. 866 68

A 40-year-old man with a large spleno-caval shunt through the azygos vein is described. This was considered a rare case, because the patient had no accompanying advanced liver disease, or episodes of hepatic encephalopathy. During checks after abnormal liver function test results, a shunt vessel was detected incidentally by ultrasonography. Computed tomography, magnetic resonance imaging, and angiography demonstrated that it was a large shunt between the splenic vein and superior vena cava through the coronary and azygos veins. The patient was a hepatitis B virus carrier and was positive for anti-HBe, and had a history of heavy drinking. However, on laparoscopic examination, the liver was not cirrhotic and the biopsy revealed only mild chronic hepatitis without bridging fibrosis. There were no esophageal varices or hepatosplenomegaly. On hemodynamic evaluation, the wedge hepatic vein pressure was slightly elevated and hepatic blood flow was reduced to half the normal value. Despite the large portal-systemic shunt, the patient had no history or signs of hepatic encephalopathy. The clinical features of this rare case are discussed.
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PMID:Large spleno-caval shunt not accompanied by cirrhosis or encephalopathy. 868 May 52

Four newborn infants with Down syndrome and manifestations of neonatal leukemia are described. One of the four was stillborn, two died shortly after birth, and a fourth survived and all evidence of leukemia disappeared in the first month of life. Three of the four cases had hydrops fetalis, and a fourth was a macerated stillborn. Nine other similar reported cases are reviewed. We conclude that neonatal leukemia in Down syndrome is a form of leukemia that is usually transient, with spontaneous recovery, but may be fatal at or around the time of birth with manifestations of hydrops fetalis, hepatosplenomegaly, and/or progressive liver disease.
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PMID:Hydrops fetalis and neonatal leukemia in Down syndrome. 871 5

Inherited mutations of the Fas/Apo1/CD95 gene, a cell-surface receptor involved in cell death signaling and in the control of self-reactivity, characterize the recently identified autoimmune lymphoproliferative syndromes. A patient with type 2 autoimmune hepatitis with the immunologic and genetic features of autoimmune lymphoproliferative syndrome is described. The clinical picture was dominated by liver disease with hepatosplenomegaly and positivity for anti-liver-kidney microsome 1 and anti-liver-cytosol 1 antibodies. A marked increase in CD3+CD4-CD8-T lymphocytes and inherited mutations in Fas alleles that led to the expression of a soluble form of the protein were also found. Fas-mediated apoptosis was deficient in the patient as it was in her mother and her sister, who carried the same allele 2 mutation. This observation links type 2 autoimmune hepatitis, an organ-specific disease, with a genetically determined defect in peripheral tolerance control.
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PMID:Fas/Apo1 mutations and autoimmune lymphoproliferative syndrome in a patient with type 2 autoimmune hepatitis. 961 60

The biological activity of blood coagulation factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen and prekallikrein was assessed in 15 healthy subjects and 60 patients with endemic Egyptian hepatosplenomegaly. The degree of liver disease was graded according to the Child-Pugh classification, the intensity of S. mansoni infection was monitored by determination of circulating schistosome immune complexes (CSIC) level using a monoclonal antibody and hemostasis activation was detected by measurement of hemostatic markers D-dimer and prothrombin fragment 1 + 2 (F1+2). Functional activity of antithrombin III, alpha2-antiplasmin and protein C as well as quantitative determination of plasma concentrations of alpha1-antitrypsin, C1 activator inhibitor and alpha2-macroglobulin were also carried out. The progressive deterioration of liver function which matched the severity of the disease and the intensity of schistosomal infection led to a reduction in anticoagulant proteins (decreases in antithrombin III and protein C) resulting in hypercoagulability and thrombin generation (increased F1+2) subsequently followed by consumption (prolongation of coagulation screening tests, thrombocytopenia, hypofibrinogenemia and decreased factor VIII resulting in hypocoagulability and secondary fibrinolysis (increased D-dimer and decreased alpha2-antiplasmin). A significant decline in fibrinogen and factors VII, XII and prekallikrein was detected in bleeders compared with ascitic patients. The decline in factor XII was closely related to CSIC high titers in all disease groups, but was not correlated to D-dimer or F1+2 concentrations. This suggests that circulating schistosome immune complexes may exert an inhibitory effect on contact factor XII which should be taken into account when considering the reasons for schistosomal coagulopathy and bleeding in hepatosplenic schistosomiasis.
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PMID:The coagulation profile in hepatosplenic schistosomiasis. 962 18

We describe two patients with mevalonate kinase deficiency and prominent hematologic abnormalities and cholestatic liver disease. Patient R.B. was not anemic at birth, but developed petechiae and cutaneous extramedullary hematopoiesis, hepatosplenomegaly, leukocytosis, and recurrent febrile events without positive bacterial or viral cultures. Patient N.M. manifested minor anomalies, hepatosplenomegaly, anemia, thrombocytopenia, recurrent febrile crises, and facial rashes. Mevalonic aciduria was found by urinary organic acid analysis, and mevalonate kinase deficiency was documented in both. The clinical spectrum of normocytic hypoplastic anemia, leukocytosis, thrombocytopenia, and abnormal blood cell forms led to diagnoses of congenital infection, myelodysplastic syndromes, or chronic leukemia in these patients before recognition of mevalonate kinase deficiency. Mevalonate kinase deficiency represents a single-gene abnormality that may be associated with significant hematologic findings. Recognition of the variability of this disorder with some patients manifesting only mild neurologic findings, yet significant hepatosplenomegaly, normocytic anemia, thrombocytopenia, and leukocytosis is important for all specialists who need to be aware of this organic aciduria.
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PMID:Hematological abnormalities and cholestatic liver disease in two patients with mevalonate kinase deficiency. 971 5

Deficiency of 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-HSDH), the enzyme that catalyses the second reaction in the principal pathway for the synthesis of bile acids, has been reported to present with prolonged neonatal jaundice with the biopsy features of neonatal hepatitis. It has also been shown to present between the ages of 4 and 46 months with jaundice, hepatosplenomegaly, and steatorrhoea (a clinical picture resembling progressive familial intrahepatic cholestasis). This paper reports two children with 3beta-HSDH deficiency who developed rickets during infancy and did not develop clinically evident liver disease until the age of 3 years. Bile acid replacement resulted in considerable clinical and biochemical improvement. The importance of thorough investigation of fat soluble vitamin deficiencies in infancy is emphasised.
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PMID:An inborn error of bile acid synthesis (3beta-hydroxy-delta5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets. 1020 55


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