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)

A variant strain of Rauscher leukemia virus (RLV-A) obtained from a transplantable murine monomyelocytic leukemia causes a disease characterized by frank anemia, wasting, hepatosplenomegaly and erythroblastosis. The involvement of platelets in this disease are reported here. The RLV-A induced a severe thrombocytopenia (25 percent of control level) at the terminal stage of disease. This thrombocytopenia was not associated with disseminated intravascular coagulopathy since the prothrombin times were always within normal limits. The partial thromboplastin time was elevated in the terminal stages of disease and was found to be associated with factor deficiencies, possibly owing to the presence of anti-factor antibodies, in the intrinsic coagulation pathway, especially factor VIII. Further, splenectomy did not abolish the thrombocytopenia, since splenectomized, virally infected animals also developed severe thrombocytopenia (29 percent of control levels). The ensuing splenomegaly during progression of disease was not the cause of the thrombocytopenia. A physiological response to the severe thrombocytopenia was the production of larger size platelets. At terminal stages of the disease, platelet volume increased to 4.2 mu 3 (normal is 3.0 mu 3). An increase in platelet volume was also observed in splenectomized, virally infected animals. Electron microscopy indicated that these circulating platelets contained c-type viral particles. Viral infection was associated with decreased life span of circulating platelets, as measured by 75Se-methionine at mid and terminal stages of the disease. Our results suggest that direct viral infection of platelets and/or megakaryocytes with subsequent cell lysis is a possible cause of the observed thrombocytopenia observed in RLVA-induced disease and may also occur in other retrovirally-induced diseases.
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PMID:Thrombocytopenia in a retrovirally-induced murine erythroleukemia. 145 28

Metabolic studies are described in a patient who presented at 3 weeks of age with severe anaemia, hyperbilirubinaemia and hypotonicity. Clinically, glycogen storage disease type II (Pompe disease) was suspected because of a massively enlarged heart and hepatosplenomegaly. This was confirmed biochemically by the demonstration of glycogen accumulation in skeletal muscle and undetectable acid alpha-1,4-glucosidase activity in fibroblasts. Further biochemical studies in this patient surprisingly revealed homocystinuria and methylmalonic aciduria, suggesting a defect in the uptake, transport or intracellular metabolism of vitamin B12. Studies in cultured fibroblasts from the patient revealed a low uptake of [57Co]cyanocobalamin and an impaired intracellular conversion to both 5'-deoxyadenosylcobalamin and methylcobalamin. Moreover, the incorporation of labelled propionate into proteins as well as the formation of labelled methionine from labelled 5-methyltetrahydrofolate was deficient in fibroblasts from the patient. Complementation studies revealed the presence of the cblC mutation in this patient. No treatment was initiated and the patient died at the age of 31 days. We conclude that the patient was affected by both glycogen storage disease type II and cblC disease. The remarkable combination of these two rare inborn errors can be the result of the consanguinity of the parents.
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PMID:Clinical and biochemical observations in a patient with combined Pompe disease and cblC mutation. 153 54

The acute form of tyrosinemia type I usually causes severe hepatocellular dysfunction. We report a 4-month-old infant with hepatosplenomegaly, ascites, and multiple intrahepatic mass lesions mimicking hepatoma. A marked increase of serum alpha-fetoprotein (97.6 micrograms/ml) and multiple small low-density lesions in the liver demonstrated by computed tomography suggested the presence of hepatoma. The liver specimens obtained at laparatomy showed mixed nodular cirrhosis with fatty metamorphosis. Serum levels of tyrosine (6.6 mg/100 ml) and methionine (5.9 mg/100 ml) were increased. Urinary organic acid analyses disclosed increased excretions of succinylacetone (1,330 mg/g creatinine) and delta-amino-levulinic acid (113.6 mg/g creatinine). Histological abnormalities and biochemical evidences led to the correct diagnosis. This case emphasizes the need for complete investigations of puzzling cases and warns against undue reliance on noninvasive imaging techniques.
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PMID:An acute form of tyrosinemia type I with multiple intrahepatic mass lesions. 169 41

A 1-3/12-year-old Turkish boy born of consanguineous parents was hospitalized in poor general condition with disorientation, hepatosplenomegaly, and rickets. Laboratory tests showed pronounced symptoms of hepatic dysfunction, rickets, and Fanconi's syndrome with acidosis. The diagnosis juvenile type I tyrosinemia was based on the anamnesis, hepatorenal symptoms, and elevated tyrosine and methionine blood levels as well as the pathognomic findings of heavy succinylacetonuria and absent fumarylacetoacetase activity in the fibroblasts. Etiology, pathobiochemistry, clinical symptoms, differential diagnosis, and therapy of this rare autosomal-recessive inherited metabolic disease were discussed.
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PMID:[Juvenile form of tyrosinemia type I]. 260 Dec 81

A child with intractable seizures from the age of 10 months and developmental retardation developed jaundice and hepatosplenomegaly at 23 months. She died at the age of 25 months. Methionine and tyrosine were elevated in urine, plasma, CSF, and brain. These elevations were more marked in the CNS than in the blood. 4-Hydroxyphenylpyruvate dioxygenase, an enzyme involved in the metabolism of tyrosine, was undetectable in skin fibroblasts and liver. This finding together with other biochemical data suggest that our case had an inherited disorder of tyrosine metabolism, in the category of tyrosinemia I. Disturbances of tyrosine and methionine metabolism in the CNS in tyrosinemia I may be more important than has been realized. The disorder should be considered in children with unexplained epilepsy and in those who develop hepatic dysfunction while on anticonvulsants.
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PMID:Tyrosinemia and intractable seizures. 661 Dec 56

Haematological symptoms can be helpful for the diagnosis of metabolic diseases. A megaloblastic anemia orientates to folate and cobalamine anomalies when associated with homocystinemia and decreased plasma methionine levels, or to congenital oroticuria (hypochromia), Pearson syndrome (sideroblasts and vacuolisation of precursors) and thiamine transporter abnormality (sideroblasts) in the absence of homocystinuria. An hemolytic anemia orientates to anomalies of anaerobic glycolysis, heme synthesis, or iron metabolism, and Wilson disease. A pancytopenia orientates to organic aciduria, lysinuric protein intolerance, mevalonic aciduria and lysosomal storage diseases (Gaucher, Niemann Pick, Wolman) when hepatosplenomegaly is present. Uremic hemolytic syndrome and hemophagocytic lymphohistiocytosis respectively orientate to B12 anomalies, lysinuric protein intolerance, lysosomal storage diseases and organic aciduria.
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PMID:[Hematologic manifestations of inborn errors of metabolism]. 1220 94

Citrin deficiency (CD) is an autosomal recessive disorder with SLC25A13 as causative gene that encodes citrin, the liver-type aspartate/glutamate carrier isoform 2 (AGC2). Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), the major CD phenotype at pediatric age, has been previously reported as a self-limiting condition with clinical presentations resolving between 6 months and 1 year of life. We report the prenatal diagnosis of CD in a family with a fatal NICCD proband. The proband was a 10-month-old male presenting cough for 8 days and jaundiced skin 1 day. Physical examination revealed fever, dark jaundiced sclera and skin, hoarse breathing sounds, and hepatosplenomegaly. Laboratory tests uncovered elevated cholestatic indices, increased ammonia, and prolonged activated partial thromboplastin time and prothrombin time, and reduced fibrinogen. Sonography showed the features of liver cirrhosis. Metabolome analysis uncovered large quantity of 4-hydroxyphenyllactate and dicarboxylates in urine and increased citrulline and methionine in blood. The patient passed away due to liver failure at his age of 13.5 months. Mutation analysis revealed him a homozygote of 851del4, a four-base deletion in exon 9 of SLC25A13 gene. On request of the parents who had a second fetus, prenatal diagnosis of CD was performed by PCR-electrophoresis following amniocentesis and amniocyte culture, and demonstrated the fetus a carrier of the same mutation. The fatal proband in the present report has provided clinical evidence challenging the traditional concept on NICCD prognosis. Moreover, as the first trial on CD prenatal diagnosis, this study might open a novel area for clinical management of CD.
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PMID:Prenatal diagnosis of citrin deficiency in a Chinese family with a fatal proband. 2209 53

Clinical manifestations of Niemann-Pick type C1 (NP-C1) disease include neonatal hepatosplenomegaly and in some patients progressive liver dysfunction and failure. This study involved a 1H NMR-linked metabolomics analysis of liver samples collected from a NP-C1 disease mutant mouse model in order to explore time-dependent imbalances in metabolic pathways associated with NP-C1 liver dysfunction, including fibrosis. NP-C1 mutant (Npc1-/-; NP-C1), control (Npc1+/+; WT), and NP-C1 heterozygous mice (Npc1+/-; HET) were generated from heterozygote matings. Aqueous extracts of these liver samples collected at time points of 3, 6, 9, and 11 weeks were subjected to high-resolution NMR analysis, and multivariate (MV) metabolomics analyses of data sets acquired were performed. A MV random forests (RFs) model effectively discriminated between NP-C1 and a combined WT/HET hepatic NMR profiles with very high predictive accuracy and reliability. Key distinguishing features included significant upregulations in the hepatic concentrations of phenylalanine, tyrosine, glutamate, lysine/ornithine, valine, threonine, and hypotaurine/methionine, and diminished levels of nicotinate/niacinamide, inosine, phosphoenolpyruvate, and 3-hydroxyphenylacetate. Quantitative pathway topological analysis confirmed that imbalances in tyrosine biosynthesis, and hepatic phenylalanine, tyrosine, glutamate/glutamine, and nicotinate/niacinamide metabolism were involved in the pathogenesis of NP-C1 disease-associated liver dysfunction/damage. 1H NMR-linked metabolomics analysis provides valuable biomarker information regarding hepatic dysfunction or damage in NP-C1 disease.
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PMID:1H NMR-Linked Metabolomics Analysis of Liver from a Mouse Model of NP-C1 Disease. 2750 74