glycogen and Syndrome

Insulin resistance is defined as a clinical state in which a normal or elevated insulin level produces an attenuated biologic response. Specifically, the biologic response most studied is insulin-stimulated glucose disposal, yet the precise cellular mechanism responsible is not yet known. However, the presence of insulin resistance is observed many years before the onset of clinical hyperglycemia and the diagnosis of Type 2 diabetes. Insulin resistance at this stage appears to be significantly associated with a clustering of cardiovascular risk factors predisposing the individual to accelerated cardiovascular disease. An overview of insulin resistance and the associated clinical insulin resistant state will be discussed.

Topics: Animals; Biological Transport; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Glycogen; Humans; Hyperglycemia; Insulin; Insulin Resistance; Models, Chemical; Signal Transduction; Syndrome

Overtraining can be defined as "training-competition > > recovery imbalance", that is assumed to result in glycogen deficit, catabolic > anabolic imbalance, neuroendocrine imbalance, amino acid imbalance, and autonomic imbalance. Additional non-training stress factors and monotony of training exacerbate the risk of a resulting overtraining syndrome. Short-term overtraining called overreaching which can be seen as a normal part of athletic training, must be distinguished from long-term overtraining that can lead to a state described as burnout, staleness or overtraining syndrome. Persistent performance incompetence, persistent high fatigue ratings, altered mood state, increased rate of infections, and suppressed reproductive function have been described as key findings in overtraining syndrome. An increased risk of overtraining syndrome may be expected around 3 weeks of intensified/prolonged endurance training at a high training load level. Heavy training loads may apparently be tolerated for extensive periods of time if athletes take a rest day every week and use alternating hard and easy days of training. Persistent performance incompetence and high fatigue ratings may depend on impaired or inhibited transmission of ergotropic (catabolic) signals to target organs, such as: (I) decreased neuromuscular excitability, (II) inhibition of alpha-motoneuron activity (hypothetic), (III) decreased adrenal sensitivity to ACTH (cortisol release) and increased pituitary sensitivity to GHRH (GH release) resulting in a counter-regulatory shift to a more anabolic endocrine responsibility, (IV) decreased beta-adrenoreceptor density (sensitivity to catecholamines), (V) decreased intrinsic sympathetic activity, and (VI) intracellular protective mechanisms such as increased synthesis of heat-shock proteins (HSP 70) represent a complex strategy against an overload-dependent cellular damage.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Affect; Amino Acids; Autonomic Nervous System; Burnout, Professional; Catecholamines; Fatigue; Glycogen; Growth Hormone-Releasing Hormone; Heat-Shock Proteins; Human Growth Hormone; Humans; Hydrocortisone; Infections; Motor Neurons; Neuromuscular Junction; Neurosecretory Systems; Physical Endurance; Pituitary Gland; Psychomotor Performance; Receptors, Adrenergic, beta; Reproduction; Risk Factors; Sports; Stress, Physiological; Stress, Psychological; Sympathetic Nervous System; Syndrome

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.

Topics: Adult; Creatine Kinase; Glycogen; Humans; Male; Middle Aged; Muscle Cramp; Muscle Proteins; Muscles; Muscular Atrophy; Phosphorylase Kinase; Physical Exertion; Syndrome; X Chromosome

The cerebrohepatorenal syndrome of Zellweger (CHRS) is remarkable not only for a distinctive combination of congenital anomalies, but also for an unusual variety of profound metabolic disturbances. After a discussion of the clinical diagnosis of CHRS, abnormalities in the metabolism of peroxisomes, mitochondria, iron, pipecolic acid, glycogen, bile acids, and organic acids are discussed and related to the clinical and other biochemical findings in the syndrome. Attention is also drawn to syndromes with biochemical or clinical abnormalities similar to those of CHRS. Although the biochemical findings indicate major abnormalities in oxidative metabolism, the primary defect remains obscure.

Topics: Abnormalities, Multiple; Amino Acids, Dicarboxylic; Bile Acids and Salts; Brain Diseases; Glutarates; Glycogen; Humans; Iron; Kidney Diseases; Liver Diseases; Microbodies; Mitochondria; Pipecolic Acids; Syndrome

Topics: Cardiomyopathies; Fibroblasts; Glucose; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Infusions, Parenteral; Leukocytes; Liver; Male; Maltose; Microscopy, Electron; Muscles; Placenta; Skin; Syndrome

Topics: Adolescent; Alanine; Alanine Transaminase; Aspartate Aminotransferases; Diabetes Mellitus, Type 1; Female; Glycogen; Growth Disorders; Hepatomegaly; Humans; Liver; Syndrome

Topics: Adolescent; Aspartate Aminotransferases; Diabetes Mellitus, Type 1; Female; Fibrosis; gamma-Glutamyltransferase; Glycogen; Hepatocytes; Hepatomegaly; Humans; Liver; Liver Diseases; Portal System; Syndrome

PRKAG2 cardiac syndrome is a distinct form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular pre-excitation and progressive cardiac conduction disorder. However, it remains unclear how mutations in the PRKAG2 gene give rise to such a complicated disease. To investigate the underlying molecular mechanisms, we generated disease-specific hiPSC-derived cardiomyocytes from two brothers both carrying a heterozygous missense mutation c.905G>A (R302Q) in the PRKAG2 gene and further corrected the R302Q mutation with CRISPR-Cas9 mediated genome editing. Disease-specific hiPSC-cardiomyocytes recapitulated many phenotypes of PRKAG2 cardiac syndrome including cellular enlargement, electrophysiological irregularities and glycogen storage. In addition, we found that the PRKAG2-R302Q mutation led to increased AMPK activities, resulting in extensive glycogen deposition and cardiomyocyte hypertrophy. Finally we confirmed that disrupted phenotypes of PRKAG2 cardiac syndrome caused by the specific PRKAG2-R302Q mutation can be alleviated by small molecules inhibiting AMPK activity and be rescued with CRISPR-Cas9 mediated genome correction. Our results showed that disease-specific hiPSC-CMs and genetically-corrected hiPSC-cardiomyocytes would be a very useful platform for understanding the pathogenesis of, and testing autologous cell-based therapies for, PRKAG2 cardiac syndrome.

Topics: Adult; AMP-Activated Protein Kinases; Base Sequence; Calcium; Cardiomegaly; Cell Differentiation; Electrophysiological Phenomena; Glycogen; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Male; Mitochondria; Models, Biological; Mutation; Myocardial Contraction; Myocytes, Cardiac; Oxidation-Reduction; Phenotype; Reproducibility of Results; Syndrome

A mechanistic cause for Mauriac syndrome, a syndrome of growth failure and delayed puberty associated with massive liver enlargement from glycogen deposition in children with poorly controlled type 1 diabetes, is unknown. We discovered a mutation in the catalytic subunit of liver glycogen phosphorylase kinase in a patient with Mauriac syndrome whose liver extended into his pelvis. Glycogen phosphorylase kinase activates glycogen phosphorylase, the enzyme that catalyzes the first step in glycogen breakdown. We show that the mutant subunit acts in a dominant manner to completely inhibit glycogen phosphorylase kinase enzyme activity and that this interferes with glycogenolysis causing increased levels of glycogen in human liver cells. It is known that even normal blood glucose levels physiologically inhibit glycogen phosphorylase to diminish glucose release from the liver when glycogenolysis is not needed. The patient's mother possessed the same mutant glycogen phosphorylase kinase subunit, but did not have diabetes or hepatomegaly. His father had childhood type 1 diabetes in poor glycemic control, but lacked the mutation and had neither hepatomegaly nor growth failure. This case proves that the effect of a mutant enzyme of glycogen metabolism can combine with hyperglycemia to directly hyperinhibit glycogen phosphorylase, in turn blocking glycogenolysis causing the massive liver in Mauriac disease.

Topics: Adolescent; Diabetes Mellitus, Type 1; Glycogen; Glycogen Phosphorylase, Liver Form; Growth Disorders; Hepatomegaly; Humans; Male; Mutation; Phosphorylase Kinase; Puberty, Delayed; Syndrome

Mauriac syndrome is characterised by growth failure, cushingoid appearance and hepatomegaly which occurs in patients with insulin dependent diabetes and was first described shortly after the introduction of insulin as a treatment for the condition.. To describe the clinical features, histological findings and outcome of young people with glycogenic hepatopathy, the hepatic manifestation of Mauriac syndrome (MS).. Retrospective cohort study.. Young people with glycogenic hepatopathy.. Tertiary paediatric hepatology unit.. Thirty-one young people (16 M), median age of 15.1 years (IQR 14-16.2) presented within the study period. Median age of diagnosis of diabetes was 10 years (IQR 8-11). Median insulin requirement was 1.33 units/kg/day; median HbA1c was 96.7 mmol/mol (IQR 84.7-112.0). Growth was impaired: median height z-score was -1.01 (-1.73 to 0.4) and median body mass index (BMI) z-score was 0.28 (-0.12 to 0.67). Hepatomegaly was universal with splenomegaly in 16%. Transaminases were abnormal with a median aspartate aminotransferase (AST) of 76 IU/L and gamma glutamyltransferase of 71 IU/L. Liver biopsy was undertaken in 19 (61%). All showed enlarged hepatocytes with clear cytoplasm with glycogenated nuclei in 17. Steatosis was present in the majority. Inflammation was present in 8 (42%). Fibrosis was seen in 14 (73%) and was generally mild though 2 had bridging fibrosis. Megamitochondria were described in 7. Presence of megamitochondria correlated with AST elevation (p=0.026) and fibrosis on biopsy (p=0.007). At follow-up 17 children had normal or improved transaminases, in 13 there was no change. Transaminases followed the trend of the child's HbA1c.. Despite modern insulin regimens and monitoring in children with type 1 diabetes, MS still exists. Significant steatosis, inflammation and fibrosis were all seen in liver biopsies.

Topics: Adolescent; Biopsy; Diabetes Mellitus, Type 1; Fatty Liver; Female; Glycogen; Growth Disorders; Hepatitis; Hepatomegaly; Humans; Liver; Liver Cirrhosis; Male; Retrospective Studies; Syndrome

Low muscle glycogen levels due to consecutive days of extensive exercise have been shown to cause fatigue and thus decrements in performance. Low muscle glycogen levels could also lead to oxidation of the branched chain amino acids and central fatigue. Therefore, the questions become, can low muscle glycogen not only lead to peripheral and central fatigue but also to overtraining, and if so can overtraining be avoided by consuming sufficient quantities of carbohydrates? Research on swimmers has shown that those who were nonresponsive to an increase in their training load had low levels of muscle glycogen and consumed insufficient energy and carbohydrates. However, cyclists who increased their training load for 2 wk but also increased carbohydrate intake to maintain muscle glycogen levels still met the criteria of over-reaching (short-term overtraining) and might have met the criteria for overtraining had the subjects been followed for a longer period of time. Thus, some other mechanism than reduced muscle glycogen levels must be responsible for the development and occurrence of overtraining.

Topics: Athletic Injuries; Bicycling; Dietary Carbohydrates; Energy Metabolism; Fatigue; Glycogen; Humans; Hydrocortisone; Lactic Acid; Male; Muscle, Skeletal; Physical Education and Training; Stress, Psychological; Syndrome

The objectives of this study were to determine whether two preslaughter management treatments, rest and mixing, influence the muscle quality of porcine stress syndrome (PSS) heterozygous (Nn) market hogs and to verify the expected quality characteristics of carcasses produced from PSS-normal (NN) and PSS-susceptible (nn) animals. Twenty-nine Nn, 14 NN, and 9 nn market hogs were randomly assigned to preslaughter handling treatments. One-half of the animals in each genotype group received 16 h of rest before slaughter, and the remaining pigs were slaughtered immediately upon arrival at the Iowa State University Meat Laboratory. Within each group, half of the Nn animals were mixed with unfamiliar pigs during transport and lairage. Length, backfat, and loin muscle area (LMA) were not affected by mixing and rest treatment. The carcasses from nn pigs had less fat (P < .05) measured at the 10th rib (off midline) and last lumbar vertebra (midline) and possessed larger LMA than carcasses from NN pigs. Heterozygous pigs were intermediate for most carcass traits. Carcass pH values among heterozygous groups were not significantly different, except that the rested animals had higher ultimate pH values (P < .01) and higher 45-min pH values. Resting had no effect on pH of NN or nn pigs. The 45-min pH values of nn carcasses were lower (P < .01) than those of NN carcasses, but ultimate pH values were similar. Values of unrested Nn animals were between those of NN and nn genotypes but with rest approached values of NN pigs. Loin muscle Minolta-Y and Hunter-L values from unrested Nn animals were higher ( P < .05) than those of rested Nn animals. Mixing did not influence these traits. The longissimus muscle lipid content was not influenced by treatment but differed among genotypes (P < .01). Glycogen levels of rested Nn animals tended to be lower than those of NN animals and approached those of nn pigs. Mixing of Nn animals resulted in higher (P < .05) chewiness scores of cooked loin chops. No significant cooking loss or InstronTM tenderness differences were observed between the PSS-Nn treatment groups. Even though 16 h of rest before slaughter improved the color and water-holding capacity of Nn pigs, effects were small and were much less than those that were due to the PSS gene.

Topics: Animals; Genotype; Glycogen; Heterozygote; Hydrogen-Ion Concentration; Lipids; Meat; Muscles; Rest; Stress, Physiological; Swine; Swine Diseases; Syndrome; Temperature

A mutant insulin receptor, Ser323Leu, has been reported in two severely insulin-resistant patients with Rabson-Mendenhall syndrome. In both cases, extreme hyperglycaemia could not be controlled by conventional antidiabetic therapy. The SER323Leu mutant insulin receptor is inserted normally in the plasma membrane but has very low binding affinity for insulin. A monoclonal antibody directed against the extracellular domain of the insulin receptor (83.14) can mimic the natural ligand as far as the first step after ligand binding--autophosphorylation of the intracellular domain of the receptor. We have investigated whether antibody binding can imitate autophosphorylation of the Ser323Leu mutant receptor and lead to metabolic events within the cell.. The effects of insulin and the insulin-receptor monoclonal antibody on receptor autophosphorylation and glycogen synthesis were compared in Chinese hamster ovary cells expressing the wild-type human insulin receptor, mock-transfected cells, cells expressing an insulin-receptor mutant without autophosphorylation capacity, and cells expressing the Ser323Leu mutant receptor.. Cells expressing the SER323Leu mutant receptor had very low specific insulin binding and, unlike cells expressing wild-type insulin receptors, did not show autophosphorylation or stimulation of glycogen synthesis in response to insulin. However, exposure of cells expressing the Ser323Leu mutant receptor to monoclonal antibody 83.14 resulted in autophosphorylation and stimulation of glycogen synthesis similar to that seen in cells expressing wild-type insulin receptors.. Although insulin does not bind to cells expressing the Ser323Leu mutation, insulin signalling can be mimicked by exposure of the cells to an antibody to the extracellular domain of the insulin receptor. Activation by monoclonal antibodies of mutant transmembrane receptors that show normal cell-surface expression but defective ligand binding may provide an approach to the therapy of some subtypes of inherited hormone resistance for which little effective treatment is available.

Topics: Adult; Animals; Antibodies, Monoclonal; CHO Cells; Cricetinae; Glycogen; Humans; Insulin; Insulin Resistance; Male; Mutation; Phosphorylation; Receptor, Insulin; Syndrome

A 14-year-old boy with mild mental retardation, myopathy, and nonobstructive hypertrophic cardiomyopathy (HCM) with clinical and histopathologic features consistent with lysosomal glycogen storage disease with normal acid maltase is described. The case illustrates the aggressive nature of the cardiomyopathy of this syndrome. This condition is associated with malignant ventricular arrhythmias, relentlessly progressive ventricular dilatation, dysfunction, and sudden death. It is important to recognize this unusual and malignant form of HCM to precipitate low early diagnosis by muscle biopsy. Patients with this condition would be excellent candidates for life-saving heart transplant as the myopathy and mental retardation are mild and nonprogressive. The underlying biochemical defect and mode of inheritance of this syndrome are unclear. However, a significant proportion are genetically related and thus, relatives may benefit from family screening.

Topics: Adolescent; Cardiomyopathy, Hypertrophic; Glucan 1,4-alpha-Glucosidase; Glycogen; Heart Failure; Humans; Intellectual Disability; Lysosomal Storage Diseases; Male; Syndrome

Two infant boys with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) are reported. Presenting with neonatal intestinal obstruction, they underwent laparotomies that showed megacystis, microcolon, and aperistaltic shortened small bowel without any mechanical obstruction. Patient 1 gradually improved and is developing normally at home, on a normal diet without genitourinary or gastrointestinal complaints (now 11 years old). Patient 2, who underwent vesicoamniotic drainage antenatally, never developed adequate gastrointestinal or genitourinary function in spite of appropriate diversion and pharmacologic support. He showed progressive deterioration and died at the age of 7 months. Detailed histo-immuno- and ultrastructural pathology assessment, although confirming results in the existing literature in some aspects, showed previously unreported neuronal dysplastic changes associated with increased laminin and fibronectin. Although patient 1 showed ultrastructural features of vacuolar degeneration of smooth muscle as reported in the literature, patient 2 showed ultrastructural and histochemical evidence of excessive smooth muscle cell glycogen storage with severely reduced contractile fibres displaced to the extreme periphery of the cells, suggesting a fundamental defect of glycogen-energy utilization. A deficiency of fiber synthesis as the alternative primary defect is discussed. In both cases, a two-step genetic defect may explain the variability in clinical outcome and pathological findings.

Topics: Abnormalities, Multiple; Colon; Energy Metabolism; Fatal Outcome; Female; Fibronectins; Glycogen; Humans; Infant; Infant, Newborn; Intestinal Obstruction; Laminin; Male; Microscopy, Electron; Muscle, Smooth; Peristalsis; Pregnancy; Syndrome; Urinary Bladder

A 21-year-old man with childhood-onset mental retardation, non-obstructive hypertrophic cardiomyopathy, and vacuolar myopathy is presented. A histopathological study of biopsied skeletal muscle showed lysosomal glycogen storage mimicking acid maltase deficiency, but biochemical analysis showed normal acid alpha-glucosidase activity. Glycogenosomes were also recognized in endothelial cells on electronmicroscopic examination of biopsied skeletal muscle. Magnetic resonance imaging (MRI) findings in the head revealed the involvement of the central nervous system. This is a new type of lysosomal glycogen storage disease with multisystemic involvement. The specific biochemical defect in this disorder remains to be elucidated.

Topics: Adult; alpha-Glucosidases; Autophagy; Brain; Cardiomyopathies; Glycogen; Glycogen Debranching Enzyme System; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Muscles; Muscular Diseases; Syndrome; Vacuoles

The symptoms of a myopathy permanently affecting limb girdle muscles are reported in a 31-year-old woman who has been presenting an exertional muscle pain syndrome with myoglobinuria for 20 years. Investigations revealed a slightly decreased utilization of glycogen in muscle, while its storage affected only rare type 2 fibers. Active phosphorylase was undetectable and phosphorylase b kinase activity was clearly decreased in muscle cells, but normal in erythocytes, lymphocytes and cultured fibroblasts.

Topics: Adult; Atrophy; Female; Glycogen; Glycogen Storage Disease; Glycolysis; Humans; Microscopy, Electron; Muscles; Muscular Diseases; Pain; Phosphorylase b; Phosphorylase Kinase; Physical Exertion; Syndrome

We successfully treated a patient with uveal effusion syndrome and abnormal sclera with a partial-thickness sclerectomy. Part of the sclera was immediately cultured, and the excised sclera and the cultured cells were examined by electron microscopy. The sclera demonstrated increased glycosaminoglycan-like deposits between the scleral fibers. The cultured scleral cells showed large intracellular glycogen-like deposits, which were not seen in cells cultured from two control scleras. These findings may be the result of a metabolic defect, which causes a thick, impermeable sclera in some cases of uveal effusion.

Topics: Body Fluids; Cells, Cultured; Cytoplasmic Granules; Female; Fluorescein Angiography; Glycogen; Glycosaminoglycans; Humans; Middle Aged; Sclera; Syndrome; Ultrasonography; Uveal Diseases

A 30 year old man with DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) syndrome associated with myocardial disease is reported. Echocardiographic study revealed a marked symmetric left ventricular hypertrophy. Histology of the endomyocardial biopsy specimen from the right ventricle showed severe glycogen deposition in the myocytes. This case may indicate that DIDMOAD syndrome is a hereditary systemic disease affecting multiple organs, including the myocardium.

Topics: Adult; Cardiomyopathies; Deafness; Diabetes Complications; Diabetes Insipidus; Diabetes Mellitus; Endocardium; Glycogen; Humans; Male; Myocardium; Optic Atrophy; Syndrome

Topics: Colon; Colonic Neoplasms; Esophagus; Female; Ganglioneuroma; Glycogen; Hamartoma; Humans; Hyperplasia; Middle Aged; Neoplasms, Multiple Primary; Syndrome

Electron microscopy performed in a young girl suffering from keratitis, ichthyosis, and deafness syndrome showed pathologic storage of glycogen in various types of tissues. This finding may be interpreted as evidence of an underlying inborn error of metabolism.

Topics: Child; Cytoplasm; Deafness; Female; Glycogen; Humans; Ichthyosis; Keratitis; Mitochondria; Skin; Staining and Labeling; Syndrome

The significance of ketosis in this syndrome has been evaluated from several viewpoints. With respect to acid-base considerations (pH, anion gap), ketosis was not very significant. However, with respect to sustained hyperglycemia, the combustion of less glucose than normal by the brain is critical and it is likely that ketone body metabolism plays an important role in this regard. This point can be underscored by a quantitative example. First, assume that the maximum rate of new glucose production in a fasted subject is less than 100 g of glucose per day. Second, since the brain will burn 100 g of glucose per day in a non-ketotic subject, it follows that, even in the absence of glucosuria, there will be a net daily consumption of glucose. Since the hyperglycemic individual has only an extra 100 or so g of glucose, it follows that the blood glucose concentration would approach the renal threshold in several days in the absence of ketosis. Recall that this is a minimum estimate because glucose oxidation in other organs and glucosuria will remove an additional quantity of glucose. Hyperglycemia can only be maintained in the absence of glucose intake if there is a reduced rate of glucose metabolism in the brain. The brain can diminish its rate of glucose catabolism by several mechanisms, including a diminished metabolic rate in the brain and/or the consumption of non-glucose fuels (free fatty acids or beta-hydroxybutyrate) by this organ.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetone; Acidosis; Brain; Diabetic Coma; Glucose; Glycerides; Glycerol; Glycogen; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Ketosis; Proteins; Syndrome

Two cases of ophthalmoplegia-plus are described for the first time in the national literature. The clinical picture of both patients aged 7 and 15 years exhibited a characteristic triad: external ophthalmoplegia, retinitis pigmentosa and heart conduction impairments. In one patient, this triad was supplemented by neurosensory deafness, torsion dystonia and the myopathic syndrome, and in the other one, by ichthyosis, cerebellar symptomatology, the myopathic syndrome and a marked elevation of protein in the cerebrospinal fluid. In both patients, the diagnosis was supported by electron microscopic studies of a muscular biopsy-specimen which disclosed pronounced changes in the number, structure, size and form of mitochondria as well as the presence of glycogen and lipid drops accumulating near mitochondria.

Topics: Abetalipoproteinemia; Adolescent; Arrhythmias, Cardiac; Child; Female; Glycogen; Humans; Lipid Metabolism; Mitochondria, Muscle; Muscles; Ophthalmoplegia; Retinitis Pigmentosa; Syndrome

Histologic findings are presented of 28 biopsies taken from 19 insulin-dependent children of either sex with long-standing diabetes who developed the Mauriac syndrome or forms frustes of it. Using this comprehensive material, probably the largest series of biopsies related to this problem, a detailed survey is given on morphologic liver findings associated with this rare type of chronic-diabetic decompensation of metabolism. Behaviour and extent of fat and glycogen deposits, including nuclear liver glycogen, showed marked variations. Not in all cases hepatomegaly, the main clinical symptom, was reflected by corresponding histologic findings. Liver glycogenosis alone is not pathognomonic of the Mauriac syndrome. In the decompensation phase of the disease however, liver glycogenosis is found fairly frequently, whereas in the recompensation phase hepatocytic lipid deposits are a common finding.

Topics: Adolescent; Biopsy; Cell Nucleus; Child; Diabetes Mellitus, Type 1; Female; Glycogen; Growth Disorders; Hepatomegaly; Humans; Lipids; Liver; Male; Syndrome

Data of a clinico-morphological examination of 4 patients with the ophthalmoplegic form of myopathy are presented. An electronmicroscopic examination has made it possible to disclose the primary morphological defect in the mitochondria of the patients' muscles. The mitochondrial pathology manifested itself in an increase of the number of these organelles, changes of their shape and size, structural abnormalities and presence of inclusions. The pathology of the mitochondria in muscular fibres with normal structure of the latter's contractile apparatus, gradual destruction of the mitochondria, and deepening of the destructive changes in the mitochondria in parallel to the lysis of the myofibrillary apparatus give one grounds to speak about the primary character of the mitochondrial pathology in those patients, and to regard this disease as a variant of mitochondrial myopathies.

Topics: Adult; Atrophy; Female; Glycogen; Histocytochemistry; Humans; Lipid Metabolism; Male; Mitochondria, Muscle; Muscles; Myofibrils; Ophthalmoplegia; Syndrome

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.

Topics: Adolescent; Adult; Female; Glucosyltransferases; Glycogen; Glycogen Debranching Enzyme System; Glycogen Storage Disease; Glycogen Storage Disease Type III; Histocytochemistry; Humans; Male; Microscopy, Electron; Middle Aged; Muscles; Neuromuscular Diseases; Syndrome

We found marked accumulation of glycogen in the brain in one case of the cerebro-hepato-renal syndrome (CHRS). Glycogen in the form of beta-particles was deposited freely within the nucleus, perikaryon and cell processes of neurons and glial cells. The changes involved the gray matter diffusely but were more prominent in the cerebral cortex. The patient died at the age of 4 months after a clinical course characterized by severe hypotonia, seizures, and apneic episodes. Other neuropathologic findings were developmental malformations of the central nervous systen (CNS) (pachygyria, polymicrogyria, and hypoplasia of the inferior olives), white matter abnormalities (deficiency in myelination and diffuse accumulation of sudanophilic droplets within glial cells), clusters of peculiar "globoid" histiocytes with pleomorphic lipid inclusions, and microglial nodules in gray and white matter. This unusual combination of findings is regarded as characteristic of the CHRS.

Topics: Brain; Brain Diseases; Cerebral Cortex; Glycogen; Histocytochemistry; Humans; Infant; Kidney Diseases; Liver Diseases; Male; Neuroglia; Neurons; Syndrome

A patient had Sézary syndrome and lymphocytic lymphoma. Cytoplasmic inclusions within the Sézary cells were demonstrated by histochemistry and electron microscopy to be composed of fetal-type glycogen. Results of tests for the presence of virus were negative. It is suggested that the Sézary cell represents a reversion of metabolic systems to more youthful types. Previously reported differences in diastase reactivity of the PAS-positive cytoplasmic inclusions are probably based on whether the glycogen is in fetal or mature configuration.

Topics: Chlorambucil; Cytoplasmic Granules; Dermatitis, Exfoliative; Glycogen; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Syndrome; Vincristine

A case of Reis-Bückler's dystrophy in a 36-year-old man is reported. Its clinical aspect is compared with its histological and ultrastructural features. The slight reticular opacities situated superficially in the central part of the cornea, immediately beneath the epithelium, correspond to dark, irregular deposits. These replaced the basal membrane and Bowman's membrane and are composed of granular material, glycogen granules, and short fibers. These short, curved, osmiophilic fibers whose diameter is approximately 130 A are also located inside the anterior stromal lamellae. These deposits seem to be the characteristic feature of this particular and rare dystrophy, stated as by Hogan. Their nature and origin are discussed.

Topics: Adult; Basement Membrane; Cornea; Corneal Dystrophies, Hereditary; Cytoplasmic Granules; Glycogen; Humans; Male; Syndrome

Topics: Adenylyl Cyclases; Adolescent; Carnitine; Carnitine O-Palmitoyltransferase; Enflurane; Glycogen; Humans; Methyl Ethers; Muscles; Muscular Diseases; Myoglobinuria; Necrosis; Syndrome

Topics: Adenosine Triphosphate; Animals; Blood Glucose; Creatine Kinase; Female; Glycogen; Hydrogen-Ion Concentration; Lactates; Male; Muscles; Muscular Diseases; Pituitary Hormones, Anterior; Stress, Physiological; Swine; Swine Diseases; Syndrome

When compared to normal megakaryocytes, those from a patient with the giant platelet syndrome exhibited numerous cytochemical abnormalities. These reflected disturbances in the metabolism of RNA, glycogen, arginine-rich histone, and various glycolytic enzymes. Ultrastructural studies of the abnormal megakaryocytes also showed decreased glycogen and RNA (ribosomes) as well as aberrations of nuclear lobulation.

Topics: Blood Platelet Disorders; Blood Platelets; Esterases; Glycogen; Histocytochemistry; Histones; Humans; Male; Megakaryocytes; Microscopy, Electron; Middle Aged; RNA; Syndrome; Thrombocytopenia

Topics: Carbohydrate Metabolism; Carbohydrate Metabolism, Inborn Errors; Diabetes Mellitus, Type 1; Female; Fructose Intolerance; Galactose; Glucose; Glycogen; Homeostasis; Humans; Hydrocortisone; Hypoglycemia; Infant; Infant, Newborn; Malabsorption Syndromes; Male; Metabolic Diseases; Pregnancy; Pregnancy in Diabetics; Syndrome

Weanling male Sprague-Dawley rats received bilateral electrolytic lesions in the dorsomedial hypothalamic area by means of a direct cathodal current. Sham-operated rats served as controls. Ponderal and linear growth, obesity index, food intake, and several indices of intermediary metabolism of adipose tissue and muscle were measured. Cathodal lesions, as did anodal lesions reported on previously resulted in retardation of body weight, length, and food intake, while the obesity index remained in the normal range. Similarly, the metabolic data in adipose tissue and muscle are comparable to those from experiments in which dorsomedial lesions were placed by anodal current: incorporation of glucose into CO2 lipid, and glycogen of muscle tissue (diaphragm) were similar in DMN-lesioned rats and controls. The difference between anodal and cathodal lesions in this hypothalamic syndrome is a delay in the onset of hypophagia until about 30 days after the hypothalamic operation. The data support the concept that lesions in the hypothalamus, in general, exert their effect by destruction of neuronal assemblies, i.e., nerve cells and/or fiber tracts passing through the lesioned area.

Topics: Adipose Tissue; Animals; Animals, Newborn; Body Weight; Carbon Dioxide; Diaphragm; Feeding Behavior; Glucose; Glycogen; Growth Disorders; Hypothalamus; Hypothalamus, Middle; Insulin; Lipid Metabolism; Male; Muscles; Proteins; Rats; Syndrome

Topics: Anemia, Aplastic; Basophils; Blood Platelet Disorders; Blood Platelets; Bone Marrow; Bone Marrow Cells; Cell Membrane; Cytoplasmic Granules; Endoplasmic Reticulum; Eosinophils; Glycogen; Hematologic Diseases; Humans; Leukemia, Myeloid; Megakaryocytes; Microscopy, Electron; Mitochondria; Neutrophils; Peroxidases; Polyribosomes; Staining and Labeling; Syndrome; Vacuoles

Histochemical and histopathological staining methods were applied to muscle biopsy material from 13 patients with distal myopathy of late onset. Six cases showed slight to moderate histopathological changes and the normal distinction between Type I and Type II muscle fibres, based on their staining characteristics for myofibrillar ATPase, was well preserved. A selective Type I atrophy and an irregular distribution of oxidative enzyme and fat staining in Type I fibres were evident. In the other 7 cases, with moderate to advanced histopathological changes, there was a marked blurring of the normal difference observed in ATPase activity between Type I and TYpe II fibres. Thus, both types of fibre exhibited a high intensity of staining for myofibrillar ATPase at pH 9.4 without inhibition by acid preincubation (pH 4.3). These changes in phosphatase activity were found not only in atrophic fibres but also in normal-sized fibres without other signs of degeneration. Nuclear proliferation in chains and "ring fibres" were found. The early histopathological and histochemical changes in distal myopathy are strikingly similar to those of myotonic dystrophy.

Topics: Adenosine Triphosphatases; Adult; Aged; Cell Nucleus; Electromyography; Female; Glycogen; Humans; Lipid Metabolism; Male; Middle Aged; Muscles; Muscular Atrophy; Myofibrils; NADH Tetrazolium Reductase; Phosphorylases; Syndrome

As in previous studies of Meesmann dystrophy, intense vacuolation of the epithelium was observed. However, neither histochemical nor electron microscopical examination of the specimens showed any evidence of abnormal quantities of glycogen or the electron dense peculiar substance of Kuwabara and Ciccarelli. Electron microscopy indicated that the basic alteration leading to the manifestations of the dystrophy was electron dense bodies in the cytoplasm of the basal epithelial cells. These electron dense bodies appeared similar to lysosomes. In the more superficial cell layers, the electron dense bodies were engulfed by vacuoles that gradually increased in number and size to fill the cytoplasm and, finally, destroyed the most superficial cells.

Topics: Basement Membrane; Biopsy; Child; Cornea; Corneal Dystrophies, Hereditary; Cysts; Cytoplasm; Epithelial Cells; Epithelium; Glycogen; Humans; Lysosomes; Male; Microscopy, Electron; Syndrome; Vacuoles

In a postmortem study of 57 diabetic patients, 19 of 23 patients with blood glucose levels greater than 200 mg/100 ml in the 72-hour period before death showed the characteristic histologic findings of "lacy" vacuolation of the iris pigment epithelium as well as vacuolation of the renal tubules (Armanni-Ebstein nephropathy). Conversely, 33 of the remaining 34 patients with blood glucose levels below 200 mg/100 ml in the 72-hour period prior to death showed no vacuolation in the iris or kidney.

Topics: Blood Glucose; Diabetes Complications; Diabetic Nephropathies; Epithelium; Glycogen; Iris; Kidney Tubules; Syndrome; Vacuoles

The authors describe in biopsies from 6 cases of Werdnig-Hoffmann disease, including 2 of the more benign type, the ultrastructural typical aspects of denervation. They compare their findings with those of other workers. The striking points are the great variation in the diameter of the muscle fibres and the myofibrils, the disorganisation of the myofibrils, the sarcomeres and the filaments, with persistance of the relations between thick and thin filaments at various levels, the modifications of the Z-band and the triads in chains. The folds and the basement membrane are examined. Centrioles are present in a muscle fibre and in a satellite. Glycogen is very abundant. The nerves seem normal but some Schwann cells contain pi granules which are not observed usually at the age of the patient. The end plates and a muscle spindle are normal.

Topics: Basement Membrane; Cell Membrane; Child, Preschool; Cytoplasmic Granules; Demyelinating Diseases; Female; Glycogen; Humans; Infant; Male; Motor Endplate; Motor Neurons; Muscles; Muscular Atrophy; Myofibrils; Nerve Degeneration; Peripheral Nerves; Sarcoplasmic Reticulum; Syndrome

Subacute necrotizing encephalomyelopathy (SNE) has been observed in an infant with regressing psychomotor development. The concentrations of alanine, pyruvate and lactate were increased in the serum and blood as well as in the cerebrospinal fluid. Pyruvate carboxylase activity was reduced in the liver tissue. An inhibitor of thiamine-pyrophosphate-ATP-phosphotransferase was present in the urine. Thiamine treatment was followed by a decrease of serum alanine and blood pyruvate and lactate, but there was no clinical improvement during a period of 17 months. Ultrastructural investigations revealed high glycogen levels in liver tissue and skeletal muscle. These findings contrast with decreased gluconeogenesis, which is suggested by the diminished pyruvate carboxylase activity. Therefore it is concluded that reduced hepatic pyruvate carboxylase activity is not the primary cause of SNE.

Topics: Alanine; Brain Stem; Encephalomalacia; Female; Glycogen; Humans; Infant; Intellectual Disability; Lactates; Liver; Liver Glycogen; Muscles; Psychomotor Disorders; Pyruvate Carboxylase; Pyruvates; Syndrome; Thiamine

Topics: Aflatoxins; Animals; Blood Glucose; Brain Diseases; Drug Synergism; Enterovirus Infections; Fatty Acids, Unsaturated; Fatty Liver; Glycogen; Hexachlorocyclohexane; Hypoglycemia; Liver; Mengovirus; Mice; Microscopy, Electron; Mitochondria, Liver; Polychlorinated Biphenyls; Rats; Reye Syndrome; Syndrome; Toxins, Biological; Triglycerides; Valerates

Topics: Acid Phosphatase; Axons; Biopsy; Child, Preschool; Diagnosis, Differential; Disulfides; Glycogen; Hair; Histocytochemistry; Humans; Male; Microscopy, Electron; NADH, NADPH Oxidoreductases; Neurofibrils; Peripheral Nervous System Diseases; Schwann Cells; Skin Manifestations; Sulfhydryl Compounds; Syndrome; Tetrazolium Salts; Thiamine Pyrophosphate

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adult; Blepharoptosis; Deglutition Disorders; Facial Paralysis; Female; Glycogen; Hearing Disorders; Humans; Lipid Metabolism; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Myofibrils; NADH, NADPH Oxidoreductases; Neuromuscular Diseases; Ophthalmoplegia; Pedigree; Speech Disorders; Syndrome

Topics: Diabetes Mellitus; Diabetic Nephropathies; Glycogen; Humans; Kidney; Kidney Papillary Necrosis; Kidney Tubules; Syndrome

Topics: Aged; Brain; Carbohydrate Metabolism, Inborn Errors; Dementia; Electroencephalography; Female; Glycogen; Histocytochemistry; Humans; Muscles; Muscular Atrophy; Peripheral Nerves; Spinal Cord; Syndrome; Tremor

Topics: Adolescent; Biopsy; Cardiomyopathies; Diagnosis, Differential; Electromyography; Glucosidases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Male; Microscopy, Electron; Muscles; Muscular Dystrophies; Myofibrils; Syndrome

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Creatine Kinase; Fructose-Bisphosphate Aldolase; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Humans; Ischemia; Lactates; Male; Muscles; Muscular Diseases; Phosphorylase Kinase; Physical Exertion; Pyruvates; Syndrome

Topics: Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Infant; Liver; Obesity; Organ Size; Syndrome

Topics: Abortion, Therapeutic; Adult; Amniocentesis; Amnion; Cardiomyopathies; Cells, Cultured; Clinical Enzyme Tests; Consanguinity; Female; Fetus; Germany, West; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Infant Mortality; Infant, Newborn; Lysosomes; Male; Microscopy, Electron; Muscle Tonus; Muscles; Pregnancy; Pregnancy Complications; Prenatal Diagnosis; Syndrome

Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Blood Proteins; Electric Stimulation; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Lactates; Lipid Metabolism; Male; Muscles; Muscular Diseases; Pyruvates; Seizures; Syndrome

Topics: Action Potentials; Child; Child, Preschool; Congenital Hypothyroidism; Creatine Kinase; Electromyography; Female; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Hypertrophy; Hypothyroidism; L-Lactate Dehydrogenase; Lipid Metabolism; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Neuromuscular Junction; Sarcoplasmic Reticulum; Syndrome; Thyroxine

Topics: Animals; DNA, Neoplasm; Female; Glucose; Glycogen; Glycolysis; Lactates; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Experimental; Oxygen Consumption; Rats; RNA, Neoplasm; Syndrome; Thiotepa

Topics: Adipose Tissue; Adolescent; Age Factors; Animals; Biological Assay; Carbon Isotopes; Child; Child, Preschool; Diaphragm; Female; Glucose Tolerance Test; Glycogen; Humans; Insulin; Insulin Secretion; Lipodystrophy; Male; Muscles; Prediabetic State; Puberty; Rats; Syndrome; Time Factors

Topics: Autoradiography; Blood Glucose; Carbon Isotopes; Erythrocytes; Female; Galactose; Glucagon; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Leukocytes; Liver; Liver Diseases; Male; Muscles; Pedigree; Syndrome; Transferases

Topics: Animals; Cardiomegaly; Glucosidases; Glycogen; Glycogen Storage Disease; Heart Defects, Congenital; Heart Diseases; Male; Microscopy, Electron; Rats; Syndrome

Topics: Adult; Aphonia; Child; Child, Preschool; Chronaxy; Citric Acid Cycle; Demyelinating Diseases; Energy Metabolism; Female; Glycogen; Histocytochemistry; Humans; Infant; Leukodystrophy, Metachromatic; Male; Middle Aged; Muscles; Muscular Atrophy; Nerve Degeneration; Syndrome