Glycogen Storage Diseases

2018 ◽  
Author(s):  
Tammy Wang ◽  
Jocelyn Wong ◽  
Anita Honkanen
Keyword(s):  
Skeletal Muscles ◽  
Autosomal Recessive ◽  
Clinical Presentation ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Muscle Relaxants ◽  
Storage Diseases ◽  
Glycogen Storage Diseases ◽  
Organ Systems ◽  
Glucose Storage

Glycogen storage diseases result from deficiencies of various enzymes or proteins in the pathways of glycogen metabolism. The reduction in effective glucose storage and/or mobilization results in hypoglycemia and accumulation of glycogen in tissues. Diagnosis can occur at any age, from infancy to adulthood, depending on the pathway affected and the degree of enzyme deficiency. The clinical presentation varies, but the most commonly affected organ systems include the heart, liver, and skeletal muscles. In addition to the morbidity that can occur from dysfunction of these organs, important anesthetic implications include administration of glucose-containing fluids to avoid hypoglycemia, monitoring for acidosis, and caution with use of depolarizing muscle relaxants because of the potential risk of hyperkalemia and rhabdomyolysis. Inheritance is commonly autosomal recessive.

scholarly journals Biochemical and clinical aspects of glycogen storage diseases

2018 ◽  
Vol 238 (3) ◽  
pp. R131-R141 ◽  
Author(s):  
Sara S Ellingwood ◽  
Alan Cheng
Keyword(s):  
Genetic Disorders ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Clinical Aspects ◽  
Branch Points ◽  
Storage Diseases ◽  
Progressive Myoclonus Epilepsy ◽  
Glycogen Storage Diseases ◽  
Myoclonus Epilepsy ◽  
Chain Lengths

The synthesis of glycogen represents a key pathway for the disposal of excess glucose while its degradation is crucial for providing energy during exercise and times of need. The importance of glycogen metabolism is also highlighted by human genetic disorders that are caused by mutations in the enzymes involved. In this review, we provide a basic summary on glycogen metabolism and some of the clinical aspects of the classical glycogen storage diseases. Disruptions in glycogen metabolism usually result in some level of dysfunction in the liver, muscle, heart, kidney and/or brain. Furthermore, the spectrum of symptoms observed is very broad, depending on the affected enzyme. Finally, we briefly discuss an aspect of glycogen metabolism related to the maintenance of its structure that seems to be gaining more recent attention. For example, in Lafora progressive myoclonus epilepsy, patients exhibit an accumulation of inclusion bodies in several tissues, containing glycogen with increased phosphorylation, longer chain lengths and irregular branch points. This abnormal structure is thought to make glycogen insoluble and resistant to degradation. Consequently, its accumulation becomes toxic to neurons, leading to cell death. Although the genes responsible have been identified, studies in the past two decades are only beginning to shed light into their molecular functions.

scholarly journals Mechanism of glycogen synthase inactivation and interaction with glycogenin

2021 ◽  
Author(s):  
Laura Marr ◽  
Dipsikha Biswas ◽  
Leonard A Daly ◽  
Christopher Browning ◽  
John Pollard ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Moderate Increase ◽  
Storage Diseases ◽  
Future Studies ◽  
Glycogen Storage Diseases ◽  
Structure Lead

The macromolecule glycogen is the major glucose reserve in eukaryotes and defects of glycogen metabolism and structure lead to glycogen storage diseases and neurodegeneration. Glycogenesis begins with self-glucosylation of glycogenin (GN), which recruits glycogen synthase (GS). GS is activated by glucose-6-phosphate (G6P) and inactivated by phosphorylation, but how these opposing processes are coupled is unclear. We provide the first structure of phosphorylated human GS-GN complex revealing an autoinhibited GS tetramer flanked by two GN dimers. Phosphorylated N- and C-terminal tails from two GS protomers converge to form dynamic "spike" regions, which are buttressed against GS regulatory helices. This keeps GS in a constrained "tense" conformation that is inactive and more resistant to G6P activation. Mutagenesis that weaken the interaction between the regulatory helix and phosphorylated tails leads to a moderate increase in basal/unstimulated GS activity, supporting the idea that phosphorylation contributes to GS inactivation by constraining GS inter-subunit movement. We propose that multivalent phosphorylation supports GS autoinhibition through interactions from a dynamic "spike" region, thus allowing a "tuneable rheostat" for regulating GS activity. Our structures of human GS-GN provide new insights into the regulation of glycogen synthesis, facilitating future studies of glycogen storage diseases.

CARM1/PRMT4 is necessary for the glycogen gene expression programme in skeletal muscle cells

2012 ◽  
Vol 444 (2) ◽  
pp. 323-331 ◽  
Author(s):  
Shu-Ching Mary Wang ◽  
Dennis H. Dowhan ◽  
Natalie A. Eriksson ◽  
George E. O. Muscat
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Cells ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Skeletal Muscle Cells ◽  
Arginine Methyltransferase ◽  
Storage Diseases ◽  
Sirna Expression ◽  
Glycogen Storage Diseases

CARM1 (co-activator-associated arginine methyltransferase 1)/PRMT4 (protein arginine methyltransferase 4), functions as a co-activator for transcription factors that are regulators of muscle fibre type and oxidative metabolism, including PGC (peroxisome-proliferator-activated receptor γ co-activator)-1α and MEF2 (myocyte enhancer factor 2). We observed significantly higher Prmt4 mRNA expression in comparison with Prmt1–Prmt6 mRNA expression in mouse muscle (in vitro and in vivo). Transfection of Prmt4 siRNA (small interfering RNA) into mouse skeletal muscle C2C12 cells attenuated PRMT4 mRNA and protein expression. We subsequently performed additional qPCR (quantitative PCR) analysis (in the context of metabolism) to examine the effect of Prmt4 siRNA expression on >200 critical genes that control (and are involved in) lipid, glucose and energy homoeostasis, and circadian rhythm. This analysis revealed a strikingly specific metabolic expression footprint, and revealed that PRMT4 is necessary for the expression of genes involved in glycogen metabolism in skeletal muscle cells. Prmt4 siRNA expression selectively suppressed the mRNAs encoding Gys1 (glycogen synthase 1), Pgam2 (muscle phosphoglycerate mutase 2) and Pygm (muscle glycogen phosphorylase). Significantly, PGAM, PYGM and GYS1 deficiency in humans causes glycogen storage diseases type X, type V/McArdle's disease and type 0 respectively. Attenuation of PRMT4 was also associated with decreased expression of the mRNAs encoding AMPK (AMP-activated protein kinase) α2/γ3 (Prkaa2 and Prkag3) and p38 MAPK (mitogen-activated protein kinase), previously implicated in Wolff–Parkinson–White syndrome and Pompe Disease (glycogen storage disease type II). Furthermore, stable transfection of two PRMT4-site-specific (methyltransferase deficient) mutants (CARM1/PRMT4 VLD and CARM1E267Q) significantly repressed the expression of Gys1, Pgam2 and AMPKγ3. Finally, in concordance, we observed increased and decreased glycogen levels in PRMT4 (native)- and VLD (methylation deficient mutant)-transfected skeletal muscle cells respectively. This demonstrated that PRMT4 expression and the associated methyltransferase activity is necessary for the gene expression programme involved in glycogen metabolism and human glycogen storage diseases.

scholarly journals Hypertrophic Cardiomyopathy and Primary Restrictive Cardiomyopathy: Similarities, Differences and Phenocopies

2021 ◽  
Vol 10 (9) ◽  
pp. 1954
Author(s):  
Riccardo Vio ◽  
Annalisa Angelini ◽  
Cristina Basso ◽  
Alberto Cipriani ◽  
Alessandro Zorzi ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Restrictive Cardiomyopathy ◽  
Glycogen Storage ◽  
Left Ventricular ◽  
Pathophysiological Mechanism ◽  
Storage Diseases ◽  
Glycogen Storage Diseases ◽  
Similar Genetic Background ◽  
Ventricular Wall Thickness ◽  
And Storage

Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes. These “sarcomeric cardiomyopathies” also share diastolic dysfunction as the prevalent pathophysiological mechanism. Starting from the observation that patients with HCM and primary RCM may coexist in the same family, a characteristic pathophysiological profile of HCM with restrictive physiology has been recently described and supports the hypothesis that familiar forms of primary RCM may represent a part of the phenotypic spectrum of HCM rather than a different genetic cardiomyopathy. To further complicate this scenario some infiltrative (amyloidosis) and storage diseases (Fabry disease and glycogen storage diseases) may show either a hypertrophic or restrictive phenotype according to left ventricular wall thickness and filling pattern. Establishing a correct etiological diagnosis among HCM, primary RCM, and hypertrophic or restrictive phenocopies is of paramount importance for cascade family screening and therapy.

A novel starch for the treatment of glycogen storage diseases

2007 ◽  
Vol 30 (3) ◽  
pp. 350-357 ◽  
Author(s):  
K. Bhattacharya ◽  
R. C. Orton ◽  
X. Qi ◽  
H. Mundy ◽  
D. W. Morley ◽  
...  
Keyword(s):  
Glycogen Storage ◽  
Storage Diseases ◽  
Glycogen Storage Diseases ◽  
Novel Starch
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