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)

Three children displaying hypotonia, cardiac involvement and defects of the mitochondrial respiratory chain complexes are reported. The first case showed severe neonatal hypotonia, failure to thrive, hepatomegaly, dilation of the right cardiac cavities, profound lactic acidosis and amino aciduria. The boy died at the age of 7 weeks. In the second case hypotonia, severe cardiomyopathy, cyclic neutropenia, lactic acidosis and 3-methylglutaconic aciduria occurred. The boy died at the age of 27 months. The third case presented at the age of 16 months as an acute hypokinetic hypertrophic cardiomyopathy with transient hypotonia and mild lactic acidosis. Spontaneous clinical remission occurred. In all cases muscle biopsy was performed. Morphological studies failed to show ragged-red fibers but there was lipid storage myopathy and decreased cytochrome c oxidase activity. Biochemical studies confirmed the cytochrome c oxidase deficiency in muscle in all cases. It was associated with complex I III deficiency in case 1 and with severe deficits of all respiratory chain complexes in case 2. Post-mortem studies in case 1 indicated that complex IV was reduced in the liver but not in the heart and quantitative analysis of mtDNA revealed a depletion in muscle. Cases 1 and 2 shared some clinical features with fatal infantile myopathy associated with cytochrome c oxidase deficiency, while case 3 displayed a very unusual clinical presentation. The histochemical enzyme reaction of cytochrome c oxidase is useful for the diagnosis of mitochondrial myopathy because ragged-red fibers may be lacking. Finally, biochemical measurement of the different mitochondrial respiratory chain complexes is required because multiple defects are frequent and occasionally related to mtDNA depletion.
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PMID:Defects of the mitochondrial respiratory chain complexes in three pediatric cases with hypotonia and cardiac involvement. 132 Jun 61

In a 4.5-month-old boy presenting with marked muscular hypotonia in the neonatal period, hepatomegaly, cardiac hypertrophy, recurrent hypoglycemia, metabolic acidosis, and secondary carnitine deficiency, there was a considerable urinary excretion of 3-methylglutaconic and 3-methylglutaric acid. Estimation of 3-methylglutaconyl-CoA hydratase, 3-hydroxy-3-methylglutaryl-CoA lyase and initial enzymatic steps of cholesterol biosynthesis in cultured fibroblasts and in different tissues postmortem revealed no enzyme deficiency. Analyses of the respiratory chain in postmortem tissues demonstrated severe impairment of complex I (NADH ubiquinone oxidoreductase) and complex IV (cytochrome c oxidase) activities in skeletal muscle and reduced complex IV activity in heart.
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PMID:Multiple respiratory chain abnormalities associated with hypertrophic cardiomyopathy and 3-methylglutaconic aciduria. 769 3

Fatal infantile mitochondrial cytopathy associated with a C3303T mutation in the mitochondrial tRNA(Leu(UuR)) gene has been reported clinically, biochemically and genetically. Here we have analyzed the percentage of this mutation in various autopsied tissues, and also in single muscle fibers using a micromanupulator, to evaluate the correlation between the pathology and heteroplasmic condition using polymerase chain reaction/restriction fragment length polymorphism. A 5-month-old Japanese girl was admitted to our hospital showing generalized muscle weakness, hepatomegaly, and cardiomegaly with lactic acidosis, and died at 6 months of age. Skeletal muscle showed severe degenerating myopathy found to be full of ragged-red fibers (RRFs), an increased number of lipid droplets, and severe cytochrome c oxidase (COX) deficiency. Microscopically hepatocytes showed massive accumulation in lipid droplets, and the heart muscle showed a network pattern suggesting metabolic cardiomyopathy. The activities of respiratory chain enzyme complex I and complex IV in the skeletal muscle were significantly decreased to 23.4% and 5.0%, respectively, of the control value. The percentage of C3303T mutation in the patient tissues were variable, and ranged from 25% in the pancreas to 99% in the spinal cord. By single fiber analysis, the percentages of C3303T mutation in RRFs with COX negative (group 1; 42.4+/-7.0) and with COX positive (group 2; 58.2+/-5.8) were significantly higher than in non RRFs with normal COX staining (group 3; 10.7+/-6.3) (both P>0.001). Our patient showed a fatal infantile form of encephalopathy, myopathy and cardiomyopathy associated with widely distributed C3303T mutation in all of somatic cells.
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PMID:Inter- and/or intra-organ distribution of mitochondrial C3303T or A3243G mutation in mitochondrial cytopathy. 1127 74

The patient had hepatomegaly with liver dysfunction at the age of 1 month. Magnetic resonance imaging performed at the age of 1 year showed multiple nodules of varying size in his liver. We were able to examine the mitochondrial respiratory chain function in the liver biopsy samples because all other differential diagnoses for hepatic cirrhosis had been ruled out. Complex I and IV activities were below the normal level (<30%) of the citrate synthase (CS) ratio. Liver blue native polyacrylamide gel electrophoresis showed an extremely weak complex I and IV band. Liver respiratory chain complexes I and IV were found to be deficient in this patient. The histologic findings were highly suggestive of mitochondrial respiratory chain disorder. Findings of progressive liver cirrhosis changes were observed in magnetic resonance imaging at the age of 5 years. An examination of the mitochondrial respiratory chain function should be performed along with a liver biopsy if mitochondrial respiratory chain disorder is suspected as a possible differential diagnosis of idiopathic hepatitis.
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PMID:Case of an infant with hepatic cirrhosis caused by mitochondrial respiratory chain disorder. 2391 Aug 10

We report on the clinical, neuropathological, and genetic findings of a Japanese case with myocerebrohepatopathy spectrum (MCHS) disorder due to polymerase gamma (POLG) mutations. A girl manifested poor sucking and failure to thrive since 4 months of age and had frequent vomiting and developmental regression at 5 months of age. She showed significant hypotonia and hepatomegaly. Laboratory tests showed hepatocellular dysfunction and elevated protein and lactate levels in the cerebrospinal fluid. Her liver function and neurologic condition exacerbated, and she died at 8 months of age. At autopsy, fatty degeneration and fibrosis were observed in the liver. Neuropathological examination revealed white matter-predominant spongy changes with Alzheimer type II glia and loss of myelin. Enzyme activities of the respiratory chain complex I, III, and IV relative to citrate synthase in the muscle were normal in the biopsied muscle tissue, but they were reduced in the liver to 0%, 10%, and 14% of normal values, respectively. In the liver, the copy number of mitochondrial DNA compared to nuclear DNA was reduced to 3.3% of normal values as evaluated by quantitative polymerase chain reaction. Genetic analysis revealed compound heterozygous mutations for POLG (I1185T/A957V). This case represents the differential involvement of multiple organs and phenotype-specific distribution of brain lesions in mitochondrial DNA depletion disorders.
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PMID:Myocerebrohepatopathy spectrum disorder due to POLG mutations: A clinicopathological report. 2546 40