glycogen and Glycogen-Storage-Disease-Type-I

Topics: Animals; Diabetes Mellitus, Type 2; Glucose; Glucosides; Glycogen; Glycogen Storage Disease Type I; Hypoglycemia; Rats

The glycogen storage diseases are a group of inherited metabolic disorders that are characterized by specific enzymatic defects involving the synthesis or degradation of glycogen. Each disorder presents with a set of symptoms that are due to the underlying enzyme deficiency and the particular tissues that are affected. Autophagy is a process by which cells degrade and recycle unneeded or damaged intracellular components such as lipids, glycogen, and damaged mitochondria. Recent studies showed that several of the glycogen storage disorders have abnormal autophagy which can disturb normal cellular metabolism and/or mitochondrial function. Here, we provide a clinical overview of the glycogen storage disorders, a brief description of autophagy, and the known links between specific glycogen storage disorders and autophagy.

Topics: Animals; Autophagy; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogenolysis; Humans; Muscle, Skeletal

Glycogen storage diseases (GSDs) type I (GSDI) and type III (GSDIII), the most frequent hepatic GSDs, are due to defects in glycogen metabolism, mainly in the liver. In addition to hypoglycemia and liver pathology, renal, myeloid, or muscle complications affect GSDI and GSDIII patients. Currently, patient management is based on dietary treatment preventing severe hypoglycemia and increasing the lifespan of patients. However, most of the patients develop long-term pathologies. In the past years, gene therapy for GSDI has generated proof of concept for hepatic GSDs. This resulted in a recent clinical trial of adeno-associated virus (AAV)-based gene replacement for GSDIa. However, the current limitations of AAV-mediated gene transfer still represent a challenge for successful gene therapy in GSDI and GSDIII. Indeed, transgene loss over time was observed in GSDI liver, possibly due to the degeneration of hepatocytes underlying the physiopathology of both GSDI and GSDIII and leading to hepatic tumor development. Moreover, multitissue targeting requires high vector doses to target nonpermissive tissues such as muscle and kidney. Interestingly, recent pharmacological interventions or dietary regimen aiming at the amelioration of the hepatocyte abnormalities before the administration of gene therapy demonstrated improved efficacy in GSDs. In this review, we describe the advances in gene therapy and the limitations to be overcome to achieve efficient and safe gene transfer in GSDs.

Topics: Animals; Clinical Trials as Topic; Dependovirus; Disease Models, Animal; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Hepatocytes; Humans; Hypoglycemia; Liver; Transgenes

Glycogen storage disease type I and glycogenic hepatopathy are the most common type of primary and secondary hepatic glycogenosis, with presenting common radiological features of hepatomegaly, hepatic signal, or density change. Beyond that, glycogen storage disease type I shows hepatocellular adenomas or fatty liver, while glycogenic hepatopathy does not.

Topics: Diagnosis, Differential; Glycogen; Glycogen Storage Disease Type I; Humans; Liver; Liver Diseases; Magnetic Resonance Imaging; Predictive Value of Tests; Tomography, X-Ray Computed

Glycogen storage disorders (GSDs) are inborn errors of metabolism with abnormal storage or utilization of glycogen. The present review focuses on recent advances in hepatic GSD types I, III and VI/IX, with emphasis on clinical aspects and treatment.. Evidence accumulates that poor metabolic control is a risk factor for the development of long-term complications, such as liver adenomas, low bone density/osteoporosis, and kidney disease in GSD I. However, mechanisms leading to these complications remain poorly understood and are being investigated. Molecular causes underlying neutropenia and neutrophil dysfunction in GSD I have been elucidated. Case series provide new insights into the natural course and outcome of GSD types VI and IX. For GSD III, a high protein/fat diet has been reported to improve (cardio)myopathy, but the beneficial effect of this dietary concept on muscle and liver disease manifestations needs to be further established in prospective studies.. Although further knowledge has been gained regarding pathophysiology, disease course, treatment, and complications of hepatic GSDs, more controlled prospective studies are needed to assess effects of different dietary and medical treatment options on long-term outcome and quality of life.

Topics: Animals; Cardiomyopathies; Diet, Carbohydrate-Restricted; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Disease Models, Animal; Glycogen; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Glycogen Storage Disease Type VI; Humans; Liver; Liver Cirrhosis

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

Topics: 1,4-alpha-Glucan Branching Enzyme; Animals; Bacteria; Biodegradation, Environmental; Chick Embryo; Chickens; Glucosidases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Goats; Humans; Liver; Mice; Mutation; Rabbits; Sugar Phosphates

Topics: Adipose Tissue; Adult; Blood Glucose; Carbohydrate Metabolism; Child; Child, Preschool; Female; Gluconeogenesis; Glucose; Glucose-6-Phosphate Isomerase; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycoside Hydrolases; Hepatomegaly; Humans; Infant; Infant, Newborn; Liver; Male; Muscles; Myoglobinuria; Phosphofructokinase-1; Phosphoglucomutase; Phosphorylases

Topics: Animals; Blood Cells; Cricetinae; Cytoplasm; Dogs; Epinephrine; Fetus; Glucocorticoids; Glucose-6-Phosphatase; Glucosyltransferases; Glycogen; Glycogen Storage Disease Type I; Glycoside Hydrolases; Gonadal Steroid Hormones; Guinea Pigs; Humans; Intestines; Kidney; Membranes; Mice; Muscles; Phosphotransferases; Rabbits; Rats

Topics: Animals; Blood Glucose; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Hydrolases; Kinetics; Models, Biological; Models, Chemical; N-Glycosyl Hydrolases; Phosphotransferases; Pyrophosphatases; Rats

Topics: Blood Cells; Blood Platelets; Erythrocytes; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Leukocytes; Phagocytosis

Topics: Digestive System; Female; Gastrointestinal Diseases; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycoside Hydrolases; Humans; Male

Topics: Amylases; Biochemical Phenomena; Biochemistry; Classification; Enzymes; Glucose-6-Phosphatase; Glucosidases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Liver Diseases; Lysosomes; Metabolism; Oligosaccharides; Pentosephosphates; Phosphoglucomutase; Phosphorylase Kinase; Polysaccharides

Mutations in. We utilized an inducible mouse model of GSD1b, TM-G6PT. In proximal tubule cells, G6PT suppression stimulates the upregulation and activity of hexokinase-I, which increases availability of the reabsorbed glucose for intracellular metabolism. Dapagliflozin prevented glycogen accumulation and improved kidney morphology by promoting a metabolic switch from glycogen synthesis toward lysis and by restoring expression levels of the main proximal tubule functional markers.. We provide proof of concept for the efficacy of dapagliflozin in preserving kidney function in GSD1b mice. Our findings could represent the basis for repurposing this drug to treat patients with GSD1b.

Topics: Animals; Disease Models, Animal; Glucose; Glycogen; Glycogen Storage Disease Type I; Kidney; Kidney Tubules, Proximal; Mice; Sodium-Glucose Transporter 2

Glycogen storage disorders occur due to enzyme deficiencies in the glycogenolysis and gluconeogenesis pathway, encoded by 26 genes. GSD's present with overlapping phenotypes with variable severity. In this series, 57 individuals were molecularly confirmed for 7 GSD subtypes and their demographic data, clinical profiles and genotype-phenotype co-relations are studied. Genomic DNA from venous blood samples was isolated from clinically affected individuals. Targeted gene panel sequencing covering 23 genes and Sanger sequencing were employed. Various bioinformatic tools were used to predict pathogenicity for new variations. Close parental consanguinity was seen in 76%. Forty-nine pathogenic variations were detected of which 27 were novel. Variations were spread across GSDIa, Ib, III, VI, IXa, b and c. The largest subgroup was GSDIII in 28 individuals with 24 variations (12 novel) in AGL. The 1620+1G>C intronic variation was observed in 5 with GSDVI (PYGL). A total of eleven GSDIX are described with the first Indian report of type IXb. This is the largest study of GSDs from India. High levels of consanguinity in the local population and employment of targeted sequencing panels accounted for the range of GSDs reported here.

Topics: Asian People; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Mutation

Glycogen storage diseases (GSDs) represent a model of pathological accumulation of glycogen disease in the kidney that, in animal models, results in nephropathy due to abnormal autophagy and mitochondrial function. Patients with Glycogen Storage Disease 1a (GSD1a) accumulate glycogen in the kidneys and suffer a disease resembling diabetic nephropathy that can progress to renal failure. In this study, we addressed whether urine-derived epithelial cells (URECs) from patients with GSD1a maintain their biological features, and whether they can be used as a model to study the renal and metabolic phenotypes of this genetic condition. Studies were performed on cells extracted from urine samples of GSD1a and healthy subjects. URECs were characterized after the fourth passage by transmission electron microscopy and immunofluorescence. Reactive oxygen species (ROS), at different glucose concentrations, were measured by fluorescent staining. We cultured URECs from three patients with GSD1a and three healthy controls. At the fourth passage, URECs from GSD1a patients maintained their massive glycogen content. GSD1a and control cells showed the ciliary structures of renal tubular epithelium and the expression of epithelial (E-cadherin) and renal tubular cells (aquaporin 1 and 2) markers. Moreover, URECs from both groups responded to changes in glucose concentrations by modulating ROS levels. GSD1a cells were featured by a specific response to the low glucose stimulus, which is the condition that more resembles the metabolic derangement of patients with GSD1a. Through this study, we demonstrated that URECs might represent a promising experimental model to study the molecular mechanisms leading to renal damage in GSD1a, due to pathological glycogen storage.

Topics: Epithelial Cells; Glucose; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Kidney; Phenotype; Reactive Oxygen Species

Glycogen storage disease type Ia (GSD Ia) is caused by autosomal mutations in glucose-6-phosphatase α catalytic subunit (G6PC) and can present with severe hypoglycemia, lactic acidosis and hypertriglyceridemia. In both children and adults with GSD Ia, there is over-accumulation of hepatic glycogen and triglycerides that can lead to steatohepatitis and a risk for hepatocellular adenoma or carcinoma. Here, we examined the effects of the commonly used peroxisomal proliferated activated receptor α agonist, fenofibrate, on liver and kidney autophagy and lipid metabolism in 5-day-old G6pc -/- mice serving as a model of neonatal GSD Ia. Five-day administration of fenofibrate decreased the elevated hepatic and renal triglyceride and hepatic glycogen levels found in control G6pc -/- mice. Fenofibrate also induced autophagy and promoted β-oxidation of fatty acids and stimulated gene expression of acyl-CoA dehydrogenases in the liver. These findings show that fenofibrate can rapidly decrease hepatic glycogen and triglyceride levels and renal triglyceride levels in neonatal G6pc -/- mice. Moreover, since fenofibrate is an FDA-approved drug that has an excellent safety profile, our findings suggest that fenofibrate could be a potential pharmacological therapy for GSD Ia in neonatal and pediatric patients as well as for adults. These findings may also apply to non-alcoholic fatty liver disease, which shares similar pathological and metabolic changes with GSD Ia.

Topics: Acyl-CoA Dehydrogenases; Animals; Animals, Newborn; Autophagosomes; Autophagy; Fatty Acids; Fenofibrate; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Kidney; Lipid Metabolism; Liver; Mice; Mice, Knockout; Microscopy, Electron, Transmission; PPAR alpha; Triglycerides

Glycogen storage disease (GSD) type 1a is an inborn error of metabolism caused by defective glucose-6-phosphatase catalytic subunit (G6PC) activity. Patients with GSD 1a exhibit severe hepatomegaly due to glycogen and triglyceride (TG) accumulation in the liver. We have shown that the activity of carbohydrate response element binding protein (ChREBP), a key regulator of glycolysis and de novo lipogenesis, is increased in GSD 1a. In the current study, we assessed the contribution of ChREBP to nonalcoholic fatty liver disease (NAFLD) development in a mouse model for hepatic GSD 1a.. Liver-specific G6pc-knockout (L-G6pc. Attenuation of hepatic ChREBP induction in GSD 1a liver aggravates hepatomegaly because of further accumulation of glycogen and lipids as a result of reduced glycolysis and suppressed VLDL-TG secretion. TM6SF2, critical for VLDL formation, was identified as a ChREBP target in mouse liver. Altogether, our data show that enhanced ChREBP activity limits NAFLD development in GSD 1a by balancing hepatic TG production and secretion.

Topics: Adipose Tissue, White; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Dependovirus; Disease Models, Animal; Gene Knockdown Techniques; Genetic Vectors; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Glycolysis; Hepatocytes; Humans; Lipogenesis; Lipoproteins, VLDL; Liver; Male; Mice; Mice, Knockout; Non-alcoholic Fatty Liver Disease; RNA, Small Interfering; Triglycerides

Glucose-6-phosphatase α (G6Pase) deficiency, also known as von Gierke's Disease or Glycogen storage disease type Ia (GSD Ia), is characterized by decreased ability of the liver to convert glucose-6-phosphate to glucose leading to glycogen accumulation and hepatosteatosis. Long-term complications of GSD Ia include hepatic adenomas and carcinomas, in association with the suppression of autophagy in the liver. The G6pc-/- mouse and canine models for GSD Ia were treated with the pan-peroxisomal proliferator-activated receptor agonist, bezafibrate, to determine the drug's effect on liver metabolism and function. Hepatic glycogen and triglyceride concentrations were measured and western blotting was performed to investigate pathways affected by the treatment. Bezafibrate decreased liver triglyceride and glycogen concentrations and partially reversed the autophagy defect previously demonstrated in GSD Ia models. Changes in medium-chain acyl-CoA dehydrogenase expression and acylcarnintine flux suggested that fatty acid oxidation was increased and fatty acid synthase expression associated with lipogenesis was decreased in G6pc-/- mice treated with bezafibrate. In summary, bezafibrate induced autophagy in the liver while increasing fatty acid oxidation and decreasing lipogenesis in G6pc-/- mice. It represents a potential therapy for glycogen overload and hepatosteatosis associated with GSD Ia, with beneficial effects that have implications for non-alcoholic fatty liver disease.

Topics: Animals; Autophagy; Bezafibrate; Disease Models, Animal; Dogs; Glucose; Glucose-6-Phosphatase; Glucose-6-Phosphate; Glycogen; Glycogen Storage Disease Type I; Lipid Metabolism; Liver; Mice; Mice, Knockout; Triglycerides

Topics: Adult; Diabetes Complications; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Glycogen; Glycogen Storage Disease Type I; Hepatomegaly; Humans; Liver; Liver Diseases; Liver Neoplasms; Male; Tomography, X-Ray Computed

In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We present a GSD III liver natural history study in children to better understand changes in hepatic parameters with age.. We reviewed clinical, biochemical, histological, and radiological data in pediatric patients with GSD III, and performed a literature review of GSD III hepatic findings.. Liver fibrosis can occur at an early age, and may explain the decrease in aminotransferases and Glc

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Cholesterol; Female; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Humans; Liver; Liver Cirrhosis; Liver Diseases; Male; Oligosaccharides; Transaminases; Triglycerides; Young Adult

Topics: Animals; Autophagy; Disease Models, Animal; Fatty Acids; Fatty Liver; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Liver; Mice; Mice, Knockout; Mitochondria, Liver; Organelle Biogenesis; Organophosphonates; Oxidation-Reduction; Thyroid Hormone Receptors beta; Triglycerides

The respective contributions to endogenous glucose production (EGP) of the liver, kidney and intestine vary during fasting. We previously reported that the deficiency in either hepatic or intestinal gluconeogenesis modulates the repartition of EGP via glucagon secretion (humoral factor) and gut-brain-liver axis (neural factor), respectively. Considering renal gluconeogenesis reportedly accounted for approximately 50% of EGP during fasting, we examined whether a reduction in renal gluconeogenesis could promote alterations in the repartition of EGP in this situation.. We studied mice whose glucose-6-phosphatase (G6Pase) catalytic subunit (G6PC) is specifically knocked down in the kidneys (K-G6pc. Compared with WT mice, K-G6pc. A diminution in renal gluconeogenesis that is accompanied by a decrease in blood vitamin D promotes a novel repartition of EGP among glucose producing organs during fasting, featured by increased intestinal gluconeogenesis that leads to sparing glycogen stores in the liver. Our data suggest a possible involvement of a crosstalk between the kidneys and intestine (via the vitamin D system) and the intestine and liver (via a neural gut-brain axis), which might take place in the situations of deficient renal glucose production, such as chronic kidney disease.

Topics: Animals; Blood Glucose; Fasting; Gluconeogenesis; Glucose; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Hypoglycemia; Insulin; Kidney; Liver; Liver Glycogen; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Vitamin D

OBJECTIVE To characterize clinical findings for polysaccharide storage myopathy (PSSM) in warmblood horses with type 1 PSSM (PSSM1; caused by mutation of the glycogen synthase 1 gene) and type 2 PSSM (PSSM2; unknown etiology). SAMPLE Database with 3,615 clinical muscle biopsy submissions. PROCEDURES Reported clinical signs and serum creatine kinase (CK) and aspartate aminotransferase (AST) activities were retrospectively analyzed for horses with PSSM1 (16 warmblood and 430 nonwarmblood), horses with PSSM2 (188 warmblood and 646 nonwarmblood), and warmblood horses without PSSM (278). Lameness examinations were reviewed for 9 warmblood horses with PSSM2. Muscle glycogen concentrations were evaluated for horses with PSSM1 (14 warmblood and 6 nonwarmblood), warmblood horses with PSSM2 (13), and horses without PSSM (10 warmblood and 6 nonwarmblood). RESULTS Rhabdomyolysis was more common for horses with PSSM1 (12/16 [75%] warmblood and 223/303 [74%] nonwarmblood) and nonwarmblood horses with PSSM2 (221/436 [51%]) than for warmblood horses with PSSM2 (39/147 [27%]). Gait abnormality was more common in warmblood horses with PSSM2 (97/147 [66%]) than in warmblood horses with PSSM1 (1/16 [7%]), nonwarmblood horses with PSSM2 (176/436 [40%]), and warmblood horses without PSSM (106/200 [53%]). Activities of CK and AST were similar in warmblood horses with and without PSSM2. Muscle glycogen concentrations in warmblood and nonwarmblood horses with PSSM1 were significantly higher than concentrations in warmblood horses with PSSM2. CONCLUSIONS AND CLINICIAL RELEVANCE Rhabdomyolysis and elevated muscle glycogen concentration were detected in horses with PSSM1 regardless of breed. Most warmblood horses with PSSM2 had stiffness and gait abnormalities with CK and AST activities and muscle glycogen concentrations within reference limits.

Topics: Animals; Biopsy; Female; Glycogen; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Synthase; Horse Diseases; Horses; Male; Muscular Diseases; Mutation; Polysaccharides; Retrospective Studies; Rhabdomyolysis

The liver maintains glucose and lipid homeostasis by adapting its metabolic activity to the energy needs of the organism. Communication between hepatocytes and extracellular environment via endocytosis is key to such homeostasis. Here, we addressed the question of whether endosomes are required for gluconeogenic gene expression. We took advantage of the loss of endosomes in the mouse liver upon Rab5 silencing. Strikingly, we found hepatomegaly and severe metabolic defects such as hypoglycemia, hypercholesterolemia, hyperlipidemia, and glycogen accumulation that phenocopied those found in von Gierke's disease, a glucose-6-phosphatase (G6Pase) deficiency. G6Pase deficiency alone can account for the reduction in hepatic glucose output and glycogen accumulation as determined by mathematical modeling. Interestingly, we uncovered functional alterations in the transcription factors, which regulate G6Pase expression. Our data highlight a requirement of Rab5 and the endosomal system for the regulation of gluconeogenic gene expression that has important implications for metabolic diseases.

Topics: Animals; Computer Simulation; Diabetes Mellitus, Experimental; Endosomes; Gene Knockdown Techniques; Gluconeogenesis; Glucose; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Hepatomegaly; Hyperglycemia; Hypoglycemia; Insulin; Lipid Metabolism; Liver; Mice, Knockout; Models, Biological; Proteomics; rab5 GTP-Binding Proteins; Signal Transduction

Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (-/-) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (-/-) mice. Untreated G6pase (-/-) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia.

Topics: Animals; Bone and Bones; Dogs; Female; Genetic Therapy; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Growth Hormone; Insulin-Like Growth Factor I; Lipid Metabolism; Liver; Male; Mice; Mice, Knockout; Osteogenesis; Radiography

Genetic deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage disease type Ia (GSD-Ia, also known as von Gierke disease; MIM 232200), an autosomal recessive disorder of metabolism associated with life-threatening hypoglycemia and growth retardation. We tested whether helper-dependent adenovirus (HDAd)-mediated hepatic delivery of G6Pase would lead to prolonged survival and sustained correction of the metabolic abnormalities in G6Pase knockout (KO) mice, a model for a severe form of GSD-Ia. An HDAd vector encoding G6Pase was administered intravenously (2 or 5 x 10(12)vector particles/kg) to 2-week-old (w.o.) G6Pase-KO mice. Following HDAd vector administration survival was prolonged to a median of 7 months, in contrast to untreated affected mice that did not survive past 3 weeks of age. G6Pase levels increased more than tenfold between 3 days and 28 weeks after HDAd injection (P < 0.03). The weights of untreated 2 w.o. G6Pase-KO mice were approximately half those of their unaffected littermates, and treatment stimulated their growth to the size of wild-type mice. Severe hypoglycemia and hypercholesterolemia, which are hallmarks of GSD-Ia both in humans and in mice, were also restored to normalcy by the treatment. Glycogen accumulation in the liver was markedly reduced. The efficacy of HDAd-G6Pase treatment in reversing the physiological and biochemical abnormalities associated with GSD-Ia in affected G6Pase-KO mice justifies further preclinical evaluation in murine and canine models of GSD-Ia.

Topics: Adenoviridae; Animals; Genetic Therapy; Genetic Vectors; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Liver; Mice; Mice, Knockout

In glycogen storage disease type 1 (GSD1), children present with severe hypoglycemia, whereas the propensity for hypoglycemia may decrease with age in these patients. It was the aim of this study to elucidate the mechanisms for milder hypoglycemia symptoms in young adult GSD1 patients. Four patients with GSD1 [body mass index (BMI) 23.2 +/- 6.3 kg/m, age 21.3 +/- 2.9 yr] and four healthy controls matched for BMI (23.1 +/- 3.0 kg/m) and age (24.0 +/- 3.1 yr) were studied. Combined (1)H/(31)P nuclear magnetic resonance spectroscopy (NMRS) was used to assess brain metabolism. Before and after administration of 1 mg glucagon, endogenous glucose production (EGP) was measured with d-[6,6-(2)H(2)]glucose and hepatic glucose metabolism was examined by (1)H/(13)C/(31)P NMRS. At baseline, GSD1 patients exhibited significantly lower rates of EGP (0.53 +/- 0.04 vs. 1.74 +/- 0.03 mg.kg(-1).min(-1); P < 0.01) but an increased intrahepatic glycogen (502 +/- 89 vs. 236 +/- 11 mmol/l; P = 0.05) and lipid content (16.3 +/- 1.1 vs. 1.4 +/- 0.4%; P < 0.001). After glucagon challenge, EGP did not change in GSD1 patients (0.53 +/- 0.04 vs. 0.59 +/- 0.24 mg.kg(-1).min(-1); P = not significant) but increased in healthy controls (1.74 +/- 0.03 vs. 3.95 +/- 1.34; P < 0.0001). In GSD1 patients, we found an exaggerated increase of intrahepatic phosphomonoesters (0.23 +/- 0.08 vs. 0.86 +/- 0.19 arbitrary units; P < 0.001), whereas inorganic phosphate decreased (0.36 +/- 0.08 vs. -0.43 +/- 0.17 arbitrary units; P < 0.01). Intracerebral ratios of glucose and lactate to creatine were higher in GSD1 patients (P < 0.05 vs. control). Therefore, hepatic defects of glucose metabolism persist in young adult GSD1 patients. Upregulation of the glucose and lactate transport at the blood-brain barrier could be responsible for the amelioration of hypoglycemic symptoms.

Topics: Adult; Blood Glucose; Brain; Butyrates; C-Reactive Protein; Fatty Acids, Nonesterified; Female; Glucose; Glycogen; Glycogen Storage Disease Type I; Humans; Insulin; Lactates; Liver; Magnetic Resonance Spectroscopy; Male; Phosphates

An elevated serum biotinidase activity in patients with glycogen storage disease (GSD) type Ia has been reported previously. The aim of this work was to investigate the specificity of the phenomenon and thus we expanded the study to other types of hepatic GSDs. Serum biotinidase activity was measured in a total of 68 GSD patients and was compared with that of healthy controls (8.7 +/- 1.0; range 7.0-10.6 mU/ml; n = 26). We found an increased biotinidase activity in patients with GSD Ia (17.7 +/- 3.9; range: 11.4-24.8; n = 21), GSD I non-a (20.9 +/- 5.6; range 14.6-26.0; n = 4), GSD III (12.5 +/- 3.6; range 7.8-19.1; n = 13), GSD VI (15.4 +/- 2.0; range 14.1-17.7; n = 3) and GSD IX (14.0 +/- 3.8; range: 7.5-21.6; n = 22). The sensitivity of this test was 100% for patients with GSD Ia, GSD I non-a and GSD VI, 62% for GSD III, and 77% for GSD IX, indicating reduced sensitivity for GSD III and GSD IX, respectively. In addition, we found elevated biotinidase activity in all sera from 5 patients with Fanconi-Bickel Syndrome (15.3 +/- 3.7; range 11.0-19.4). Taken together, we propose serum biotinidase as a diagnostic biomarker for hepatic glycogen storage disorders.

Topics: Biomarkers; Biotinidase; DNA Mutational Analysis; Glycogen; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type VI; Humans; Liver; Liver Diseases; Sensitivity and Specificity; Specimen Handling

The deficiency of glucose-6-phosphatase (G6Pase) underlies life-threatening hypoglycemia and growth retardation in glycogen storage disease type Ia (GSD-Ia). An adeno-associated virus (AAV) vector encoding G6Pase was pseudotyped as AAV8 and administered to 2-week-old GSD-Ia mice (n = 9). Median survival was prolonged to 7 months following vector administration, in contrast to untreated GSD-Ia mice that survived for only 2 weeks. Although GSD-Ia mice were initially growth-retarded, treated mice increased fourfold in weight to normal size. Blood glucose was partially corrected by 2 weeks following treatment, whereas blood cholesterol normalized. Glucose-6-phosphatase activity was partially corrected to 25% of the normal level at 7 months of age in treated mice, and blood glucose during fasting remained lower in treated, affected mice than in normal mice. Glycogen storage was partially corrected in the liver by 2 weeks following treatment, but reaccumulated to pre-treatment levels by 7 months old (m.o.). Vector genome DNA decreased between 3 days and 3 weeks in the liver following vector administration, mainly through the loss of single-stranded genomes; however, double-stranded vector genomes were more stable. Although CD8+ lymphocytic infiltrates were present in the liver, partial biochemical correction was sustained at 7 m.o. The development of efficacious AAV vector-mediated gene therapy could significantly reduce the impact of long-term complications in GSD-Ia, including hypoglycemia, hyperlipidemia and growth failure.

Topics: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Dependovirus; Genetic Therapy; Genetic Vectors; Glucose-6-Phosphatase; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycogen; Glycogen Storage Disease Type I; Immunohistochemistry; Injections, Intravenous; Kidney; Liver; Mice; Mice, Knockout; Models, Animal; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Transduction, Genetic

Thermodynamic-based constraints on biochemical fluxes and concentrations are applied in concert with mass balance of fluxes in glycogenesis and glycogenolysis in a model of hepatic cell metabolism. Constraint-based modeling methods that facilitate predictions of reactant concentrations, reaction potentials, and enzyme activities are introduced to identify putative regulatory and control sites in biological networks by computing the minimal control scheme necessary to switch between metabolic modes. Computational predictions of control sites in glycogenic and glycogenolytic operational modes in the hepatocyte network compare favorably with known regulatory mechanisms. The developed hepatic metabolic model is used to computationally analyze the impairment of glucose production in von Gierke's and Hers' diseases, two metabolic diseases impacting glycogen metabolism. The computational methodology introduced here can be generalized to identify downstream targets of agonists, to systematically probe possible drug targets, and to predict the effects of specific inhibitors (or activators) on integrated network function.

Topics: Algorithms; Animals; Biological Transport; Citric Acid Cycle; Computer Simulation; Energy Metabolism; Enzymes; Glycogen; Glycogen Storage Disease Type I; Glycogen Storage Disease Type VI; Glycolysis; Hepatocytes; Humans; Metabolic Diseases; Models, Biological; Oxidative Phosphorylation; Thermodynamics

High lactate concentrations occur in type I glycogen storage disease (GSD) whenever glycogenolysis occurs. Not only does hyperlactataemia cause acute clinical deterioration, but chronic lactate elevations have also been associated with many of the long-term complications in GSD. A portable finger-stick blood lactate meter has recently been marketed as a training tool for high-performance athletes, but it has not been tested as a clinical diagnostic tool. This study was performed to assess the accuracy of the portable lactate meter in subjects with GSD I who are predisposed to high lactate concentrations. A total of 166 intravenous and 39 capillary samples from 13 subjects were tested concomitantly on three different lactate meters. The meter readings were compared with the lactate concentration determined by the laboratory gold-standard enzymatic colorimetric assay. Almost no inter-meter variability was found. The lactate meter values had outstanding correlation with the laboratory lactate determination, although the meters were found to run 0.5 mmol/L higher than the laboratory assay. The meter deviation was independent of lactate concentration. More variability was noted with finger-stick capillary lactate determinations, but monitoring of trends with capillary samples should prove valuable as a method for determining long-term control or acute deterioration. The portable lactate meter is a highly accurate tool for monitoring lactate concentrations, and should prove valuable for monitoring metabolic control in patients with GSD type I and other disorders associated with hyperlactataemia.

Topics: Adolescent; Adult; Biochemistry; Chemistry, Clinical; Child; Child, Preschool; Colorimetry; Evaluation Studies as Topic; Female; Glucose; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Humans; Infant; Lactates; Lactic Acid; Male; Monitoring, Ambulatory; Regression Analysis; Reproducibility of Results

Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type Ia (GSD-Ia), an autosomal recessive disorder characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. G6Pase is an endoplasmic reticulum-associated transmembrane protein expressed primarily in the liver and the kidney. Therefore, enzyme replacement therapy is not feasible using current strategies, but somatic gene therapy, targeting G6Pase to the liver and the kidney, is an attractive possibility. Previously, we reported the development of a mouse model of G6Pase deficiency that closely mimics human GSD-Ia. Using neonatal GSD-Ia mice, we now demonstrate that a combined adeno virus and adeno-associated virus vector-mediated gene transfer leads to sustained G6Pase expression in both the liver and the kidney and corrects the murine GSD-Ia disease for at least 12 months. Our results suggest that human GSD-Ia would be treatable by gene therapy.

Topics: Adenoviridae; Animals; Dependovirus; Genetic Therapy; Genetic Vectors; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Kidney; Liver; Mice

Therapy in glycogen storage disease type Ia (GSD Ia), an inherited disorder of carbohydrate metabolism, relies on nutritional support that postpones but fails to prevent long-term complications of GSD Ia. In the canine model for GSD Ia, we evaluated the potential of intravenously delivered adeno-associated virus (AAV) vectors for gene therapy. In three affected canines, liver glycogen was reduced following hepatic expression of canine glucose-6-phosphatase (G6Pase). Two months after AAV vector administration, one affected dog had normalization of fasting glucose, cholesterol, triglycerides, and lactic acid. Concatamerized AAV vector DNA was confirmed by Southern blot analysis of liver DNA isolated from treated dogs, as head-to-tail, head-to-head, and tail-to-tail concatamers. Six weeks after vector administration, the level of vector DNA signal in each dog varied from one to five copies per cell, consistent with variation in the efficiency of transduction within the liver. AAV vector administration in the canine model for GSD Ia resulted in sustained G6Pase expression and improvement in liver histology and in biochemical parameters.

Topics: Animals; Blood Glucose; Cholesterol; Dependovirus; Dogs; Genetic Therapy; Genetic Vectors; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Lactic Acid; Liver; Models, Animal; Time Factors; Transduction, Genetic; Triglycerides

In type I glycogenosis, mutation of the glucose-6-phosphatase gene results in absent glucose-6-phosphatase activity in liver cells leading to fasting hypoglycemia. Liver transplantation is expected to normalize glucose homeostasis.. Endogenous glucose production (6,6 2H2 glucose) was measured after an overnight fast and during exogenous 13C-labeled glycerol infusion in a patient with glycogenosis type I 24 months after liver transplantation and in a group of healthy subjects.. Compared with healthy subjects, the glycogenosis patient had normal fasting glucose production and glucose and insulin concentrations after liver transplantation, but mildly elevated plasma glucagon concentrations. Gluconeogenesis from exogenous glycerol (13C glucose synthesis) was similar and did not lead to enhancement of glucose production in both healthy controls and the patient.. Liver glucoregulatory function is restored by orthotopic liver transplantation in type I glycogenosis.

Topics: Adolescent; Blood Glucose; Carbon Isotopes; Deuterium; Female; Glucagon; Gluconeogenesis; Glucose; Glycerol; Glycogen; Glycogen Storage Disease Type I; Humans; Insulin; Kinetics; Liver Transplantation; Reference Values

In order to investigate the glomerular size and renal localization of apolipoprotein in type Ia glycogen storage disease, a renal biopsy was performed in two proteinuric patients. Histopathological examination of the biopsy specimens revealed focal sclerotic glomerular sclerosis in both patients. The mean glomerular area was 21.6 +/- 11.6 x 10(3) microns 2, indicating enlargement of the glomeruli. Immunohistochemical staining of the specimens for apolipoprotein showed localization of apolipoprotein AI on the inner side of the glomerular capillary wall, and in proximal tubular epithelial cells. In one patient with a history of several episodes of hypoglycemia, treatment with corn starch improved the carbohydrate and lipid metabolic profile and reduced the daily urinary protein excretion from 2.23 to 0.5 g. These results suggest that focal sclerotic glomerular lesions associated with type Ia glycogen storage disease may be related to disorders of carbohydrate and lipid metabolism.

Topics: Adult; Apolipoproteins; Biopsy; Complement C3d; Fats; Glomerular Mesangium; Glycogen; Glycogen Storage Disease Type I; Humans; Immunoglobulin A; Immunoglobulin M; Immunohistochemistry; Kidney; Kidney Diseases; Kidney Glomerulus; Male; Middle Aged

Children with glycogen storage disease type I (GSD I) lack the ability to convert glucose 6-phosphate to glucose and yet are able to produce glucose endogenously. To test the hypothesis that the source of this glucose is increased cycling of glucose moieties through hepatic glycogen, six children with GSD I were studied on two occasions during which they received enteral glucose for 6 h at 35 or 50 mumol.kg-1.min-1 along with [6,6-2H2]glucose to measure plasma glucose flux and [1-13C]galactose to label intrahepatic uridyl diphosphate (UDP)-glucose. After 3 h, acetaminophen was given to estimate UDP-glucose flux (reflecting the rate of glycogen synthesis). Mean steady-state plasma glucose concentrations (4.8 +/- 0.2 vs. 5.8 +/- 0.1 mM) and total flux (34.8 +/- 1.7 vs. 47.5 +/- 2.0 mumol.kg-1.min-1) were increased (P < 0.05 or better) on the high-infusion day. Endogenous glucose production was detectable only on the low-infusion day (2.0 +/- 0.5 mumol.kg-1.min-1). UDP-glucose flux was increased (P < 0.05) on the high-infusion day (25.8 +/- 1.6 vs. 34.7 +/- 4.1), ruling out cycling of glucose moieties through glycogen with release of glucose by debrancher enzyme as the source of glucose production.

Topics: Blood Glucose; Carbon Isotopes; Child; Deuterium; Enteral Nutrition; Glucose; Glycogen; Glycogen Storage Disease Type I; Humans; Liver; Uridine Diphosphate Glucose

Glycogen storage disease type Ia (GSD-Ia) (von Gierke's disease) was identified in two 47-day-old littermate Maltese puppies. The puppies were presented for necropsy with a history of failure to thrive, mental depression, and poor body condition. Gross findings included small body size and emaciation (212 and 246 g versus 595 g for normal littermate), severely enlarged pale livers (48 and 61 g), and pale kidneys. Histologically, there was marked diffuse vacuolation of hepatocytes with large amounts of glycogen and small amounts of lipid. Renal tubular epithelium was mildly to moderately vacuolated. Soft tissue mineralization was present in renal tubules and pulmonary alveolar septa. Biochemical analysis showed that levels of glucose-6-phosphatase were markedly reduced in liver (0.3 and 0.4 microM/minute/g tissue versus 4.7 +/- 1.5 microM/minute/g tissue for controls) and kidney (0.45 and 0.4 microM/minute/g tissue versus 4.1 microM/minute/g tissue for controls) and that glycogen content was increased in liver (9.4% and 9.4% versus 1.3% +/- 1.4% for controls). This is the first confirmed report of animals with glycogen storage disease type Ia.

Topics: Animals; Body Height; Dog Diseases; Dogs; Epithelium; Female; Glucosephosphate Dehydrogenase; Glycogen; Glycogen Storage Disease Type I; Kidney; Kidney Tubules; Liver; Male; Phosphorylases

We report the case of a young child with Glycogen Storage Disease (GSD) type-Ia who developed echogenic kidneys, medullary calcium deposition and disturbance of renal function. These severe renal abnormalities are seen in young adults whose GSD-I has been ineffectively treated. Renal disease can be considered a major problem in GSD-I.

Topics: Calcium; Child, Preschool; Glycogen; Glycogen Storage Disease Type I; Humans; Infant; Kidney; Kidney Medulla; Male; Nephrocalcinosis; Ultrasonography

Hypertension and proteinuria were observed in a 2-year-old child with type IA (von Gierke's) glycogen storage disease (GSD). She had evidence of hyperfiltration and had elevated selective renal vein renins. On renal biopsy, increased mesangial cell matrix and cellularity were observed with focal thickening and irregularity of the basement membrane. This case may be representative of the early renal findings in type IA GSD.

Topics: Female; Glycogen; Glycogen Storage Disease Type I; Histocytochemistry; Humans; Hypertension, Renal; Infant; Kidney; Kidney Diseases; Proteinuria

Three children had renal histopathologic findings indicative of glycogen storage disease type I. Glomerular basement membrane (GBM) alterations were present in the three patients, particularly so in the two patients with proteinuria. Thickening, lamellation, and glycogen deposition were the characteristic alterations in the GBM. Glomerulosclerosis was prominent in one patient. We suggest that the GBM alteration is related to the glomerular sclerosis and that both are related to metabolic derangements of glycogen storage disease type I.

Topics: Adolescent; Basement Membrane; Child, Preschool; Female; Glycogen; Glycogen Storage Disease Type I; Humans; Infant, Newborn; Kidney Glomerulus; Kidney Tubules; Male; Nephrosclerosis

Topics: Adolescent; Child; Child, Preschool; Erythrocytes; Glycogen; Glycogen Debranching Enzyme System; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type IV; Humans; Infant; Leukocytes; Liver; Liver Diseases; Phosphorylase a

A biochemical study was performed in a Lapland dog suspected of glycogen storage disease type II (acid alpha-glucosidase deficiency, Pompe's disease). Glycogen content was substantially elevated in heart and skeletal muscle but not in the liver. Severely reduced activities of acid alpha-glucosidase (EC 3.2.1.20) were found in heart, skeletal muscle, liver and cultured tongue fibroblasts. The deficiency was located in the glycoprotein fraction, which supported its lysosomal origin. The electrophorogram showed after acid incubation that the affected dog was missing the activity band, while after neutral incubation the pattern was similar to control. The obtained biochemical data are compared with the known data of the human pathology.

Topics: alpha-Glucosidases; Animals; Cells, Cultured; Dog Diseases; Dogs; Female; Fibroblasts; Glucosidases; Glycogen; Glycogen Storage Disease Type I; Kinetics; Liver Glycogen; Muscles; Myocardium; Tongue

The contradictory data obtained in studies of type 1b glycogenosis would be explained by an anomeric preference for the capture of glucose-6-phosphate by hepatic microsomes. The alpha anomers of hexoses would be utilized preferentially by glycogenolysis and gluconeogenesis, while the beta anomers of hexoses would be preferentially utilized for glycolysis.

Topics: Gluconeogenesis; Glucose-6-Phosphatase; Glucosephosphates; Glycogen; Glycogen Storage Disease Type I; Glycolysis; Humans; Microsomes, Liver; Models, Biological; Permeability; Stereoisomerism; Structure-Activity Relationship

The essential biochemical characteristic of von Gierke's disease is an inborn glucose-6-phosphatase deficiency and glycogen storage in the liver and kidney. This expresses itself morphometrically as an increased volume of glycogen per unit volume of the hepatocellular cytoplasm. Since glucose-6-phosphatase activity in patients studied is practically at the zero level, and the endoplasmic reticulum loses a large part of its membrane values, we conclude that the remaining endoplasmic reticulum represents glucose-6-phosphatase free membranes. A typical structural feature of the endoplasmic reticulum in von Gieke's disease is the appearance of "double contoured vesicles" (= pockets). These vesicles comprise approximately 3,5% of the total membrane system. The mitochondria play an important role in glycolysis and glycogen synthesis. It is thus to be expected that these organelles change in terms of their morphometric parameters in the course of glycogenosis type I. An important point in this direction is numerical mitochondrion reduction in combination with an unchanged mitochondrial volume.

Topics: Child, Preschool; Endoplasmic Reticulum; Glycogen; Glycogen Storage Disease Type I; Humans; Infant; Kidney; Liver; Male; Mitochondria, Liver

Topics: Allopurinol; Bicarbonates; Blood Glucose; Diazoxide; Gluconeogenesis; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Growth Disorders; Humans; Hypoglycemia; Liver; Liver Glycogen; Uric Acid

Five patients with glycogen storage disease are described. Hypoglycemia was observed in all patients after an overnight fast, and glycemic and lactatemic curves obtained after oral administration of glucose or galactose were typical of those seen in Type III glycogenosis. An increase of liver glycogen up to 12-16% and complete absence of liver amylo-1,6-glucosidase were found in liver tissue samples obtained by needle biopsy. The patients were diagnosed as having Type III glycogenosis. In two patients the absence of amylo-1,6-glycosidase was accompanied by a sharp decline of liver phosphorylase activity. In one patient a decline of glucose-6-phosphatase activity was observed. The structure of liver glycogen was different in different patients, and so were the types of glycemic and lactatemic curves obtained upon protein tolerance tests. The above phenomena might be explained by some secondary disturbances in the activity of enzymes (phosphorylase, glucose-6-phosphatase) involved in the metabolism of liver glycogen of these patients.

Topics: Blood Glucose; Child; Child, Preschool; Erythrocytes; Female; Galactose; Glucose Tolerance Test; Glucosyltransferases; Glycogen; Glycogen Debranching Enzyme System; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Humans; Hypoglycemia; Lactates; Liver; Male; Phosphorylases

Topics: Adenylyl Cyclases; Animals; Child; Fetus; Fructose-1,6-Diphosphatase Deficiency; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Liver Glycogen; Rats

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

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diagnosis, Differential; Fasting; Female; Galactose; Glucagon; Glucose; Glucose Tolerance Test; Glucosyltransferases; Glycogen; Glycogen Storage Disease Type I; Hexosaminidases; Humans; Hydrocortisone; Hypoglycemia; Infant; Insulin; Liver; Male; Metabolism, Inborn Errors

Topics: Child; Child, Preschool; Fatty Acids, Nonesterified; Female; Fructose-Bisphosphatase; Gluconeogenesis; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Growth Hormone; Humans; Hydrocortisone; Infant; Insulin; Liver; Liver Diseases; Male; Phosphofructokinase-1

Topics: Glucosidases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycoside Hydrolases; Histocytochemistry; Histological Techniques; Humans; Liver Glycogen

Topics: Carbon Isotopes; Glucose; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycoside Hydrolases; Hepatitis; Humans; Jaundice, Chronic Idiopathic; Liver Diseases; Liver Glycogen; Molecular Weight; Muscular Diseases; Phosphorylases; Ultracentrifugation

Topics: Adolescent; Carcinoma, Hepatocellular; Cortisone; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Hepatitis; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Microscopy, Electron; Norethandrolone

Topics: Coronary Disease; Diagnosis, Differential; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycolysis; Heart Failure; Histocytochemistry; Humans; Hypokalemia; Lactates; Myocardium; Potassium; Rheumatic Heart Disease

Topics: Amylases; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans

Topics: Albinism; Alleles; Animals; Blood Glucose; Genes, Lethal; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Heterozygote; Homozygote; Kidney; Liver; Mice; Radiation Genetics; Thymus Gland

Topics: Adolescent; Adult; Blood Glucose; Child; Child, Preschool; Epinephrine; Female; Glucagon; Glucose-6-Phosphatase; Glucosidases; Glucosyltransferases; Glycerol; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Injections, Intravenous; Lactates; Liver; Liver Glycogen; Male; Muscles

Topics: Adult; Glycogen; Glycogen Storage Disease Type I; Gout; Humans; Male

Topics: Adult; Female; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Infant; Leukocytes; Male; Triamcinolone

Topics: Antihypertensive Agents; Child; Diazoxide; Drug Eruptions; Drug Hypersensitivity; Glucose Tolerance Test; Glycerides; Glycogen; Glycogen Storage Disease Type I; Humans; Hyperglycemia; Hyperlipidemias; Hypoglycemia; Insulin; Lipids; Male; Triglycerides; Xanthomatosis

Topics: Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans

Topics: Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Muscles

Topics: Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Medical Records

Topics: Carcinoma, Hepatocellular; Child; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Infant; Liver Neoplasms

Topics: Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Liver

Topics: Glycogen; Glycogen Storage Disease Type I; Heart; Humans; Phosphoric Monoester Hydrolases

Topics: Glycogen; Glycogen Storage Disease Type I; Humans; Liver; Muscles

Topics: Glycogen; Glycogen Storage Disease Type I; Humans; Liver; Muscles