glycogen and Intellectual-Disability

Topics: alpha-Glucosidases; Diagnosis, Differential; Glucan 1,4-alpha-Glucosidase; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Intellectual Disability; Lysosomes; Muscle, Skeletal; Myocardium

Congenital enzymopathic hyperlactacidemia results from a defect of utilisation of pyruvate either at the level of the pyruvate junction (pyruvate-carboxylase, pyruvate-dehydrogenase and Kreb's cycle), or at the level of the unidirectional enzymes on neo-glucogenesis and of neo-glycogenogenesis, e.g. glucose-6-phosphatase, phosphoenol-pyruvate-carboxykinase and glycogen synthetase. The enzymopathies which affect neoglucogenesis associate hyper-lactacidemia and fasting hypoglycemia and more or less marked hepatomegaly. Type I glycogenesis (von Gierke's disease) is the best known example. Enzymopathies which affect the pyruvate junction and the Krebs cycle, may be manifested in addition by: --either chronic neuropathies, e.g. Leigh's disease, recurrent ataxia, and moderate hyperalactacidemia,--or, as in congenital lactic acidoses, which have a rapid and severe prognosis with major hyperlactacidemia. Functional investigation, in particular, loading tests are of great value in orientation and justify the practice of tissue biopsy which permits the enzyme diagnosis. Recent, still unconfirmed knowledge of the pathogenesis of these diseases emphasizes the considerable importance of estimation of blood lactic acid in the investigation of metabolic acidoses of hereditary origin.

Topics: Acidosis; Ataxia; Brain Stem; Carbohydrate Metabolism, Inborn Errors; Citric Acid Cycle; Encephalomalacia; Fructose-1,6-Diphosphatase Deficiency; Glucose; Glycogen; Glycogen Storage Disease Type I; Glycogen Synthase; Humans; Infant; Infant, Newborn; Intellectual Disability; Lactates; Phosphoenolpyruvate Carboxykinase (GTP); Psychomotor Disorders; Pyruvate Carboxylase Deficiency Disease; Pyruvate Dehydrogenase Complex Deficiency Disease; Pyruvates

To elucidate the complex impact of hypoxia on adipose tissue, resulting in biased metabolism, insulin resistance and finally diabetes we used mature adipocytes derived from a Simpson-Golabi-Behmel syndrome patient for microarray analysis. We found a significantly increased transcription rate of genes involved in glycolysis and a striking association between the pattern of upregulated genes and disease biomarkers for diabetes mellitus and insulin resistance. Although their upregulation turned out to be HIF-1α-dependent, we identified further transcription factors mainly AP-1 components to play also an important role in hypoxia response. Analyzing the regulatory network of mentioned transcription factors and glycolysis targets we revealed a clear hint for directing glycolysis to glutathione and glycogen synthesis. This metabolic switch in adipocytes enables the cell to prevent oxidative damage in the short term but might induce lipogenesis and establish systemic metabolic disorders in the long run.

Topics: Adipocytes; Adipogenesis; Arrhythmias, Cardiac; Biomarkers; Cell Hypoxia; Gene Expression Profiling; Gene Expression Regulation; Genetic Diseases, X-Linked; Gigantism; Glutathione; Glycogen; Glycolysis; Heart Defects, Congenital; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Insulin Resistance; Intellectual Disability; Oligonucleotide Array Sequence Analysis; Protein Interaction Mapping; Signal Transduction; Transcription Factor AP-1; Transcription, Genetic

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

Muscle biopsies from three patients with cardiomyopathy, mental retardation and increased serum creatine kinase levels revealed scattered fibers with tiny intracytoplasmic vacuoles containing basophilic and acid phosphatase-positive material and slightly increased amounts of PAS-positive granules. These findings are consistent with those seen in the so-called lysosomal glycogen storage disease with normal acid maltase. In addition to the vacuoles, there were occasional folds or indentations in the sarcolemma which were connected to the membrane enclosing the vacuoles. These membranes were well demonstrated histochemically by the nonspecific esterase and acetylcholinesterase stains. On electron microscopy, most of the vacuoles were bounded by membranes with basal lamina. The vacuolar membrane stained positively with antibodies raised to dystrophin, dystrophin-associated glycoproteins, laminin and type 4 collagen, and it was identical to the sarcolemma and its basal lamina. Therefore, the membrane abnormality which causes sarcolemmal folding is probably critical to understanding the pathomechanism of this disease.

Topics: Adolescent; Adult; Basement Membrane; Biopsy; Cardiomyopathies; Cell Membrane; Dystrophin; Glycogen; Humans; Immunohistochemistry; Intellectual Disability; Male; Microscopy, Electron; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Sarcolemma; Staining and Labeling; Vacuoles

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

Morphological changes are shown in the muscle biopsy specimens of an 8-year-old girl who suffered from a triosephosphate isomerase (TPI) deficiency, resulting in a chronic, nonspherocytic, hemolytic anemia, mental retardation and neuromuscular impairment. The newly introduced enzyme histochemical reaction for TPI demonstrated a total lack of histochemically detectable enzyme activity, whereas biochemical analysis of muscle tissue revealed less than 10% of the normal enzyme activity. Electron microscopy showed a degenerative myopathy with an increase in the amount of intracellular glycogen. Additionally, mitochondrial changes within the muscle fibers were observed to be similar to those in mitochondrial myopathies. The disturbed balance between glycerin-aldehyde phosphate and dihydroxyacetone phosphate, due to the deficiency of the TPI enzyme, is interpreted as the biochemical background of an impaired electron transport across the mitochondrial membrane, resulting in the coexistence of an impaired glycolytic pathway and an impaired mitochondrial metabolism of muscle cells.

Topics: Carbohydrate Epimerases; Child; Female; Glycogen; Humans; Intellectual Disability; Mitochondria; Muscular Diseases; Triose-Phosphate Isomerase

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: Acid Phosphatase; Adult; Alanine; Brain Chemistry; Cerebrosides; Child, Preschool; Chromatography, Paper; Chromatography, Thin Layer; Creatinine; Female; Gangliosides; Glucuronidase; Glycine; Glycogen; Humans; Intellectual Disability; Kidney; Lipids; Liver; Male; Pedigree

Topics: Adolescent; Biopsy; Child; Child, Preschool; Female; Gangliosides; Glycogen; Glycogen Storage Disease; Golgi Apparatus; Humans; Infant; Intellectual Disability; Intestine, Small; Leukocytes; Lipid Metabolism, Inborn Errors; Lysosomes; Macrophages; Male; Microscopy, Electron; Mucopolysaccharidoses

Topics: Acid Phosphatase; Biopsy; Child; Glucosidases; Glucosyltransferases; Glucuronidase; Glycogen; Glycogen Storage Disease; Hexosaminidases; Histocytochemistry; Humans; Intellectual Disability; Male; Microscopy; Microscopy, Electron; Muscles; Muscular Atrophy; Muscular Diseases

Topics: Abnormalities, Multiple; Age Determination by Skeleton; Bone and Bones; Consanguinity; Developmental Disabilities; Female; Foot; Glycogen; Growth Disorders; Hand; Humans; Infant; Intellectual Disability; Male; Microscopy, Electron; Muscles; Muscular Atrophy; Myofibrils; Nerve Degeneration; Pedigree; Rubinstein-Taybi Syndrome; Sarcoplasmic Reticulum

Topics: Carbohydrate Metabolism, Inborn Errors; Child; Child, Preschool; Colloids; Cytoplasmic Granules; Female; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Hydrogen-Ion Concentration; Inclusion Bodies; Intellectual Disability; Iron; Kupffer Cells; Liver; Male; Microscopy; Microscopy, Electron; Oxidation-Reduction; Phosphotungstic Acid; Silver Nitrate

Topics: Adult; Biological Transport; Brain; Cerebellum; Cerebral Cortex; Cerebral Palsy; Diffuse Cerebral Sclerosis of Schilder; Dysentery; Glycogen; Hepatolenticular Degeneration; Humans; Intellectual Disability; Kernicterus; Lipidoses; Medulla Oblongata; Neuroglia; Neurons; Pons; Synapses

Topics: Adolescent; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Dwarfism; Female; Glycogen; Humans; Hypogonadism; Infant; Intellectual Disability; Male; Microcephaly; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Xeroderma Pigmentosum

Topics: Basement Membrane; Biopsy; Cell Nucleus; Child, Preschool; Cytoplasm; Extracellular Space; Female; Glycogen; Humans; Intellectual Disability; Microscopy, Electron; Muscles; Muscular Diseases; Myofibrils; Neuromuscular Diseases; Pinocytosis; Reflex, Abnormal; Sarcolemma; Thigh

Topics: Congenital Hypothyroidism; Female; Glycogen; Humans; Ichthyosis; Infant; Intellectual Disability; Linoleic Acids; Lipid Metabolism; Liver; Liver Glycogen; Microscopy, Electron; Muscle Spasticity; Myxedema; Palmitic Acids; Retinal Degeneration

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Amino Acids; Carcinoma, Hepatocellular; Child, Preschool; Cysteine; Diet Therapy; Female; Galactosemias; Glycogen; Humans; Infant; Intellectual Disability; Liver Neoplasms; Male; Maple Syrup Urine Disease; Methionine; Middle Aged; Neuroblastoma; Phenylketonurias; Portal Vein; Pyridoxine; Serine; Sulfisoxazole; Tyrosine

Topics: Congenital Hypothyroidism; Down Syndrome; Glycogen; Humans; Intellectual Disability; Myotonia