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 fatal case of systemic carnitine deficiency is reported. The patient suffered from slowly progressive muscle weakness since early childhood. After the age of 17 years her weakness progressed more rapidly until her death at the age of 20. A pregnancy during the last year of the patient's life was followed by rapid deterioration in her condition. An episode of renal insufficiency occurred at the age of 17 years and hepatomegaly, increased BSP dye retention and intermittent ketoacidosis were present during the last month of her life. Biopsy and autopsy specimens of muscle showed a lipid storage myopathy. Type 1 fibers were selectively severely affected, and many Type 1 fibers were atrophic. Abundant large mitochondria, some also containing abnormal inclusions, were also present in the muscle fibers. At autopsy there was marked accumulation of sudanophilic lipid deposits in all hepatocytes, in the renal tubular epithelial cells, and a patchy increase of lipid material was found in the myocardial fibers. There was marked carnitine deficiency in the patient's liver as well as muscel, while the carnitine palmityltransferase activities in these tissues were abnormally high. The basic metabolic abnormality is assumed to be a defect in carnitine biosynthesis.
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PMID:Fatal systemic carnitine deficiency with lipid storage in skeletal muscle, heart, liver and kidney. 18 38

Five patients, 4 men and 1 woman, had adult-onset and slowly progressive weakness. There was distal wasting in 2, hepatomegaly in 3, and congestive heart failure in 2. Electromyography showed a mixed pattern with abundant fibrillations. Serum creatine phosphokinase was increased 5- to 45-fold. Blood glucose failed to respond to epinephrine or glucagon, and venous lactate did not rise after ischemic exercise. Muscle biopsy showed vacuolar myopathy affecting both fiber types. By electron microscopy the vacuoles corresponded to large pools of glycogen not limited by a membrane. Glycogen concentration was 3 to 5 times normal in muscle and 7 to 21 times normal in erythrocytes. In the presence of iodine, muscle glycogen showed a spectrum characteristic of phosphorylase-limit-dextrin. Debrancher activity was measured by a spectrophotometric assay and by a radioactive reverse reaction. The activity was lacking in muscle and erythrocytes of 4 patients according to both assays; in 1 patient the reverse reaction was not impaired. Though previously reported in only 5 patients, debrancher deficiency myopathy may not be rare and should be considered in the differential diagnosis of adult-onset hereditary myopathies.
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PMID:Debrancher deficiency: neuromuscular disorder in 5 adults. 28 18

This report deals with two sisters who died with eight, respectively ten weeks under the signs of respiratory failure caused by progressive muscular weakness. Only an elevated cerebrospinal fluid protein was suspicious of an additional disturbance of the central nervous system. Muscle biopsy revealed a vacuolar myopathy. Histochemistry showed lipid storage, increased mitochondrial enzyme activity, and to a lower degree, glycogen accumulation especially in type I muscle fibers. Electron microscopy confirmed elevated lipid content in combination with increased, enlarged and abnormally structured mitochondria. Biochemical studies on muscle biopsy, in comparison with normal children, showed a significant decrease of carnitine content and an increased activity of carnitine palmityltransferase. Retrospectively from a clinical point of view this disease is suggestive of "systemic carnitine deficiency", even if some symptoms (hepatomegaly, cardiomyopathy) were not present and serum- and liver carnitine was not measured because the children died before the diagnosis of muscle carnitine deficiency was confirmed. The clinical picture of these two fatal cases is compared with another observation of muscle caritine deficiency. This child shows only a mild course of muscle disorder, but very similar morphological changes in muscle biopsy. Biochemically, there was a clear decrease in muscular carnitine, while the serum levels were in the normal range. The activity of muscular carnitine palmityltransferase was also normal.
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PMID:[Clinical, morphological and biochemical studies on muscle carnitine deficiency (author's transl)]. 50 58

A fatal case of carnitine deficiency is described. The patient had intermittent metabolic acidosis, fluctuating hepatomegaly, and progressive muscle weakness since 22 months of age. One of two liver biopsies revealed lipid accumulation in the hepatocytes, and a muscle biopsy at age 5 years showed a lipid storage myopathy. Type 1 fibres were the most severely affected. Satellite and vascular endothelial cells also contained abnormal lipid deposits. Quantitative electron microscopy demonstrated an approximately 50-fold increase in lipid material, and a twofold increase in mitochondria in myofibres. The muscle carnitine level was less than one-seventh of the lowest value encountered in 74 biopsies from non-weak or neuromuscular disease controls. The basic abnormality in this patient is assumed to be a defect in carnitine biosynthesis.
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PMID:Carnitine deficiency: clinical, morphological, and biochemical observations in a fatal case. 87 8

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

A 3-month-old girl was admitted to the hospital because of hypotonia and frequent vomiting. She had severe metabolic acidosis and her liver function was abnormal. Hepatomegaly and rapidly progressive liver failure developed, and she died at 4 months of age. Two half-siblings from a different mother had died in infancy of an undiagnosed myopathy. The liver was fatty and hepatocytes were filled with large and small lipid droplets. Other tissues were morphologically normal. The respiratory chain enzymes containing subunits encoded by mitochondrial DNA were markedly decreased in liver, partially decreased in muscle, but normal in other tissues. Southern blot analysis showed 90% depletion of mitochondrial DNA in liver, 53% depletion in muscle, and normal amounts in other tissues. This is the second case of fatal infantile liver failure associated with mitochondrial DNA depletion. This pathogenetic mechanism should be considered in infants with multiple respiratory chain defects and variable tissue expression.
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PMID:Fatal infantile liver failure associated with mitochondrial DNA depletion. 144 52

In this retrospective study from five centres, 139 patients over 10 years of age with glycogen storage disease types I, III, VI and IX are described. Almost half of the patients with glycogen storage disease type Ia had retarded growth and most had hyperlipidaemia. One-third of the patients had adenomas, although none of these showed malignant transformations. With increasing age the growth, liver size and hyperlipidaemia of patients with glycogen storage disease type III improve. However, there was a high incidence of myopathy and cardiomyopathy. Patients with glycogen storage disease types VI and IX had a normal growth pattern after childhood. Hepatomegaly and hypercholesterolaemia, however, were still present in half of the patients.
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PMID:The long-term outcome of patients with glycogen storage diseases. 212 9

Phosphorylase b kinase deficiency affecting muscle has been observed infrequently in children with weakness and hepatomegaly, and in 2 adults with cramps on exertion. We observed 2 additional adults with phosphorylase b kinase deficiency: Patient 1, aged 58, had progressive, predominantly distal weakness since age 46 but no cramps on exertion; Patient 2, aged 26, had cramps on exertion since age 6 but no weakness. Lactate production on ischemic exercise was impaired only in Patient 1. The serum creatine kinase level was elevated in both. Muscle specimens showed focal glycogen excess in both, and a necrotizing myopathy and mild denervation atrophy in Patient 1. Muscle phosphorylase b kinase activity was 0.5% and 8.9% of the lowest control value in Patients 1 and 2, respectively; erythrocyte phosphorylase b kinase activity was normal in both; liver phosphorylase b kinase activity, measured in Patient 1, was also normal. Other glycolytic enzymes in muscle were preserved in both.
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PMID:Adult phosphorylase b kinase deficiency. 225 64

The proband, a 17-year-old boy, was admitted to our department because of the difficulty in standing on heel. Physical examination revealed a marked weakness and atrophy of bilateral lower legs, especially anterior tibial muscles. Patellar and Achilles tendon reflexes were abolished. Marked hepatomegaly and moderate splenomegaly were noted on abdominal echogram and CT scanning. Serum creatine kinase, lactate dehydrogenase, GOT and GPT were markedly increased. There were no abnormal findings in thyroid function, serum lipid analysis and serum lactate level after ischemic forearm exercise test. EMG of anterior tibial and calf muscles showed a mixture of myogenic and neurogenic patterns and biopsy specimen of calf muscle was compatible with a dystrophic change. Liver biopsy specimen revealed no noticeable change except a slight ballooning of hepatocytes in light microscopy. However, electron microscopic examination showed a marked increase of intracellular vesicles and enlarged smooth ER in which low-density, cotton-like materials were contained. In family study, both his father and paternal uncle were also affected with advanced scapuloperoneal-type myopathy associated with a marked elevation of serum creatine kinase and hepatomegaly. The disorder differs from Miyoshi's distal muscular dystrophy, which shows an early involvement of flexor muscles in lower extremities and is inherited as an autosomal-recessive trait. Although the etiology of hepatomegaly in this case remains to be elucidated, the special findings on electron microscopic study imply the possibility of some unknown metabolic disorder involving both muscle and liver. This disease seems to be a new type of scapuloperoneal-type myopathy, probably having an autosomal-dominant inheritance.
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PMID:[Familial scapuloperoneal-type myopathy associated with a marked elevation of serum creatine kinase and hepatomegaly]. 275 61

Muscle was cultured from a 7-month-old boy affected by generalized weakness, macroglossia, cardiomegaly, hepatomegaly and increasing dyspnea. Muscle biopsy showed a vacuolar myopathy with glycogen accumulation (Pompe's disease). The muscle was cultured to verify whether the abnormality could be expressed in culture during myogenesis. In the living muscle cultures, phase-contrast microscopy revealed that myotubes as young as two weeks were vacuolated and that the vacuolization was higher in the older cultures compared to parallel control cultures. Fluorescent microscopy by acridine orange staining of the cultures showed a marked increase in acridine orange positive material (presumptive lysosomes) throughout the sarcoplasm. Electron microscopic data revealed myofibrillar destruction in the muscle biopsy and vacuolized cytoplasm in the Schwann cells. Cytochemically, the patient's myotubes stained very intensely for acid phosphatases. The increased acid phosphatase activity was quantitatively confirmed by cytophotometric evaluation performed on patient and control parallel myotubes. This is the first evidence that an increase in acid phosphatases has been quantitatively demonstrated in cultured muscle from a patient with acute infantile onset acid maltase deficiency (Pompe's disease) although the enzymatic activity was assayed at only one time of incubation.
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PMID:Infantile-acute acid maltase deficiency (Pompe's disease): studies of muscle cultures. 644 May 27


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