Read by QxMD icon Read

Glycogen storage diseases

Haiqing Yi, Fengqin Gao, Stephanie Austin, Priya S Kishnani, Baodong Sun
Patients with progressive hepatic form of GSD IV often die of liver failure in early childhood. We tested the feasibility of using recombinant human acid-α glucosidase (rhGAA) for treating GSD IV. Weekly intravenously injection of rhGAA at 40 mg/kg for 4 weeks significantly reduced hepatic glycogen accumulation, lowered liver/body weight ratio, and reduced plasma ALP and ALT activities in GSD IV mice. Our data suggests that rhGAA is a potential therapy for GSD IV.
December 2016: Molecular Genetics and Metabolism Reports
Terry D Hinds, Katherine A Burns, Peter A Hosick, Lucien McBeth, Andrea Nestor-Kalinoski, Heather A Drummond, Adbulhadi A AlAmodi, Michael W Hankins, John P Vanden Heuvel, David E Stec
Non-alcoholic fatty liver disease (NAFLD) is the most rapidly growing form of liver disease, and if left untreated can result in non-alcoholic steatohepatitis (NASH) ultimately resulting in liver cirrhosis and failure. Biliverdin reductase-A (BVRA) is a multi-functioning protein primarily responsible for the reduction of biliverdin to bilirubin. Also, BVRA can function as a kinase and transcription factor, regulating several cellular functions. We report here that liver BVRA protects against hepatic steatosis by inhibiting glycogen synthase kinase-3β (GSK3β) by enhancing serine 9 phosphorylation, which inhibits its activity...
October 10, 2016: Journal of Biological Chemistry
Carola Hedberg-Oldfors, Emma Glamuzina, Peter Ruygrok, Lisa J Anderson, Perry Elliott, Oliver Watkinson, Chris Occleshaw, Malcolm Abernathy, Clinton Turner, Nicola Kingston, Elaine Murphy, Anders Oldfors
We describe a new type of cardiomyopathy caused by a mutation in the glycogenin-1 gene (GYG1). Three unrelated male patients aged 34 to 52 years with cardiomyopathy and abnormal glycogen storage on endomyocardial biopsy were homozygous for the missense mutation p.Asp102His in GYG1. The mutated glycogenin-1 protein was expressed in cardiac tissue but had lost its ability to autoglucosylate as demonstrated by an in vitro assay and western blot analysis. It was therefore unable to form the primer for normal glycogen synthesis...
October 7, 2016: Journal of Inherited Metabolic Disease
Mireia Díaz-Lobo, Alda Lisa Concia, Livia Gómez, Pere Clapés, Ignacio Fita, Joan J Guinovart, Joan C Ferrer
Glycogen synthase (GS) and glycogen phosphorylase (GP) are the key enzymes that control, respectively, the synthesis and degradation of glycogen, a multi-branched glucose polymer that serves as a form of energy storage in bacteria, fungi and animals. An abnormal glycogen metabolism is associated with several human diseases. Thus, GS and GP constitute adequate pharmacological targets to modulate cellular glycogen levels by means of their selective inhibition. The compound 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) is a known potent inhibitor of GP...
September 26, 2016: Organic & Biomolecular Chemistry
Christopher T Turner, Maria Fuller, John J Hopwood, Peter J Meikle, Doug A Brooks
Pompe disease is caused by a deficiency in the lysosomal enzyme α-glucosidase, and this leads to glycogen accumulation in the autolysosomes of patient cells. Glycogen storage material is exocytosed at a basal rate in cultured Pompe cells, with one study showing up to 80% is released under specific culture conditions. Critically, exocytosis induction may reduce glycogen storage in Pompe patients, providing the basis for a therapeutic strategy whereby stored glycogen is redirected to an extracellular location and subsequently degraded by circulating amylases...
October 28, 2016: Biochemical and Biophysical Research Communications
Stephanie L Austin, Andrew Chiou, Baodong Sun, Laura E Case, Kenny Govendrageloo, Perrin Hansen, Priya S Kishnani
OBJECTIVE: PRKAG2 syndrome, an autosomal dominant disorder, is characterized by severe infantile hypertrophic cardiomyopathy and heart rhythm disturbances to cases with a later presentation and a spectrum of manifestations including cardiac manifestations, myopathy and seizures. The cardiac features of PRKAG2 resemble the cardiac manifestations of Pompe disease. We present a patient who was initially diagnosed with Pompe disease and treated with alglucosidase-alfa enzyme replacement therapy (ERT); however, he was eventually diagnosed to carrying a PRKAG2 pathogenic gene mutation; he did not have Pompe disease instead he was a carrier for the common adult leaky splice site mutation in the GAA gene...
September 28, 2016: Molecular Genetics and Metabolism
Eva-Maria Kuech, Graham Brogden, Hassan Y Naim
Lysosomal storage disorders are a heterogeneous group of more than 50 distinct inborn metabolic diseases affecting about 1 in 5000 to 7000 live births. The diseases often result from mutations followed by functional deficiencies of enzymes or transporters within the acidic environment of the lysosome, which mediate the degradation of a wide subset of substrates, including glycosphingolipids, glycosaminoglycans, cholesterol, glycogen, oligosaccharides, peptides and glycoproteins, or the export of the respective degradation products from the lysosomes...
September 21, 2016: Biochimie
Laure Gallay, Philippe Petiot, Isabelle Durieu, Nathalie Streichenberger, Frederic Berard
Pompe disease is an inherited lysosomal disease in which there is a decrease or absence of acid alpha-glucosidase activity. This enzyme defect induces glycogen storage in different tissues, especially muscle and heart, resulting in muscle weakness, respiratory failure and heart disease. Substitutive enzyme replacement therapy (ERT) dispensed every two weeks is the only treatment that has shown benefits. However, this treatment induces hypersensitivity for half of the treated patients. Reactions range from mild to severe, sometimes requiring ERT suspension and anti-anaphylaxis drug administration...
July 19, 2016: Neuromuscular Disorders: NMD
Benjamin Koo, Bjorn Oskarsson
Phosphoglycerate mutase enzyme deficiency in muscle causes a metabolic myopathy (glycogen storage disease X) characterized by exertional muscle contractures, weakness, hyperCKemia, and myoglobinuria. Six different autosomal recessive variants in PGAM-M have been described thus far (Salameh et al., 2013). In this case report, we report a novel disease-causing variant. A 52-year-old African-American woman presented with exertional muscle contractures, myalgias, and weakness since childhood including an episode of rhabdomyolysis...
October 2016: Neuromuscular Disorders: NMD
C A Maile, J R Hingst, K K Mahalingan, A O O'Reilly, M E Cleasby, J R Mickelson, M E McCue, S M Anderson, T D Hurley, J F P Wojtaszewski, R J Piercy
BACKGROUND: Equine type 1 polysaccharide storage myopathy (PSSM1) is associated with a missense mutation (R309H) in the glycogen synthase (GYS1) gene, enhanced glycogen synthase (GS) activity and excessive glycogen and amylopectate inclusions in muscle. METHODS: Equine muscle biochemical and recombinant enzyme kinetic assays in vitro and homology modelling in silico, were used to investigate the hypothesis that higher GS activity in affected horse muscle is caused by higher GS expression, dysregulation, or constitutive activation via a conformational change...
August 31, 2016: Biochimica et Biophysica Acta
Chang Xie, Ya-Ping Zhang, Lu Song, Jie Luo, Wei Qi, Jialu Hu, Danbo Lu, Zhen Yang, Jian Zhang, Jian Xiao, Bin Zhou, Jiu-Lin Du, Naihe Jing, Yong Liu, Yan Wang, Bo-Liang Li, Bao-Liang Song, Yan Yan
PRKAG2 cardiac syndrome is an autosomal dominant inherited disease resulted from mutations in the PRKAG2 gene that encodes γ2 regulatory subunit of AMP-activated protein kinase. Affected patients usually develop ventricular tachyarrhythmia and experience progressive heart failure that is refractory to medical treatment and requires cardiac transplantation. In this study, we identify a H530R mutation in PRKAG2 from patients with familial Wolff-Parkinson-White syndrome. By generating H530R PRKAG2 transgenic and knock-in mice, we show that both models recapitulate human symptoms including cardiac hypertrophy and glycogen storage, confirming that the H530R mutation is causally related to PRKAG2 cardiac syndrome...
October 2016: Cell Research
Chana L Glasser, Joseph A Picoraro, Preti Jain, Sivan Kinberg, Evelyn Rustia, Kara Gross Margolis, Kwame Anyane-Yeboa, Alejandro D Iglesias, Nancy S Green
Severe congenital neutropenia type IV (SCN IV) is a syndrome of severe neutropenia, cardiac and urogenital defects, prominent superficial veins, facial dysmorphism, failure to thrive (FTT), and intermittent thrombocytopenia, caused by a glucose-6-phosphatase catalytic subunit 3 (G6PC3) gene mutation. SCN IV has been linked to glycogen storage disease type 1b as both disorders involve disruption of the glucose-6-phosphatase/glucose-6-phosphate transporter complex, leading to arrested neutrophil maturation. Emerging evidence suggests that neutrophil function plays an important role in intestinal integrity, evidenced by inflammatory bowel disease in certain neutropenic patients...
October 2016: Journal of Pediatric Hematology/oncology
Edoardo Malfatti, Christine Barnerias, Carola Hedberg-Oldfors, Cyril Gitiaux, Audrey Benezit, Anders Oldfors, Robert-Yves Carlier, Susana Quijano-Roy, Norma B Romero
Glycogen storage disease type IV (GSD IV) is an autosomal recessive disorder causing polyglucosan storage in various tissues. Neuromuscular forms present with fetal akinesia deformation sequence, lethal myopathy, or mild hypotonia and weakness. A 3-year-old boy presented with arthrogryposis, motor developmental delay, weakness, and rigid spine. Whole body MRI revealed fibroadipose muscle replacement but sparing of the sartorius, gracilis, adductor longus and vastus intermedialis muscles. Polyglucosan bodies were identified in muscle, and GBE1 gene analysis revealed two pathogenic variants...
October 2016: Neuromuscular Disorders: NMD
Yohei Sato, Hiroshi Kobayashi, Takashi Higuchi, Yohta Shimada, Hiroyuki Ida, Toya Ohashi
: : Pompe disease (PD) is a lysosomal storage disease that is caused by a deficiency of the acid α-glucosidase, which results in glycogen accumulation in the lysosome. The major clinical symptoms of PD include skeletal muscle weakness, respiratory failure, and cardiac hypertrophy. Based on its severity and symptom onset, PD is classified into infantile and late-onset forms. Lysosomal accumulation of glycogen can promote many types of cellular dysfunction, such as autophagic dysfunction, endoplasmic reticulum stress, and abnormal calcium signaling within skeletal muscle...
August 18, 2016: Stem Cells Translational Medicine
Yili Lu, Liyin Wang, Jun Li, Beibei Wu, Huiping Wu, Yue Luo, Zi-Bing Jin, Xiaoou Shan
Glycogen storage disease type‑Ia (GSD‑Ia) is a rare autosomal recessive disease caused by a mutation in the gene encoding glucose‑6‑phosphate‑α (G6PC). The present study reported the case of a 3‑month‑old female Chinese patient with GSD‑Ia born to consanguineous parents. The aim of the present study was to identify the precise mutation of the G6PC gene associated with this family and to describe the phenotypic characteristics of the patient. A comprehensive examination was performed on the patient, including physical examination, vein blood gas analysis, abdominal sonography and biochemical analyses...
October 2016: Molecular Medicine Reports
Haran Yogasundaram, Ian D Paterson, Michelle Graham, Consolato Sergi, Gavin Y Oudit
No abstract text is available yet for this article.
August 2016: Circulation. Heart Failure
Valérie Decostre, Pascal Laforêt, Aleksandra Nadaj-Pakleza, Marie De Antonio, Sylvain Leveugle, Gwenn Ollivier, Aurélie Canal, Kahina Kachetel, François Petit, Bruno Eymard, Anthony Behin, Karim Wahbi, Philippe Labrune, Jean-Yves Hogrel
Glycogen storage disease type III is an inherited metabolic disorder characterized by liver and muscle impairment. This study aimed to identify promising muscle function measures for future studies on natural disease progression and therapeutic trials. The age-effect on the manual muscle testing (MMT), the hand-held dynamometry (HHD), the motor function measure (MFM) and the Purdue pegboard test was evaluated by regression analysis in a cross-sectional retrospective single site study. In patients aged between 13 and 56 years old, the Purdue pegboard test and dynamometry of key pinch and knee extension strength were age-sensitive with annual losses of 1...
September 2016: Neuromuscular Disorders: NMD
A Schänzer, D Faas, S Rust, T Podskarbi, A B P van Kuilenburg, M Scarpa, A Kunze, T Marquardt, A Hahn
No abstract text is available yet for this article.
September 2016: Klinische Pädiatrie
Monika Gjorgjieva, Margaux Raffin, Adeline Duchampt, Ariane Perry, Anne Stefanutti, Marie Brevet, Antonin Tortereau, Laurence Dubourg, Aurélie Hubert-Buron, Mylène Mabille, Coralie Pelissou, Louis Lassalle, Philippe Labrune, Gilles Mithieux, Fabienne Rajas
Glycogen storage disease type I (GSDI) is a rare metabolic disease due to glucose-6 phosphatase deficiency, characterized by fasting hypoglycemia. Patients also develop chronic kidney disease whose mechanisms are poorly understood. To decipher the process, we generated mice with a kidney-specific knockout of glucose-6 phosphatase (K.G6pc(-/-) mice) that exhibited the first signs of GSDI nephropathy after 6 months of G6pc deletion. We studied the natural course of renal deterioration in K.G6pc(-/-) mice for 18 months and observed the progressive deterioration of renal functions characterized by early tubular dysfunction and a later destruction of the glomerular filtration barrier...
July 19, 2016: Human Molecular Genetics
Philippa J Rohman, Elaine Scott, Linda Richfield, Uma Ramaswami, Derralynn A Hughes
AIM: Glycogen storage disease type II (GSD II or Pompe disease; OMIM; 232 300) is a rare autosomal recessive lysosomal storage disorder resulting from deficiency of α-glucosidase and accumulation of glycogen in muscle. Clinical symptoms include weakness of skeletal and respiratory muscles and, in infants, cardiomyopathy. Patients with GSD II receive infusions of recombinant α-glucosidase (enzyme replacement therapy; ERT), which slow the progression of the disease. ERT is given to male and female patients of all ages but as yet little is documented on the effects of continuing ERT during pregnancy...
July 7, 2016: Journal of Obstetrics and Gynaecology Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"