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Glycogen storage disease

Glycogen storage disease

Kreuder, J. Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa: an observational study. Keutzer, Storae.

Glycogen storage disease -

The most promising treatments are then moved into clinical trials, with the goal of identifying new ways to safely and effectively prevent, screen for, diagnose, or treat a disease.

Speak with your doctor about the ongoing progress and results of these trials to get the most up-to-date information on new treatments. Participating in a clinical trial is a great way to contribute to curing, preventing and treating liver disease and its complications.

Start your search here to find clinical trials that need people like you. Glycogen Storage Disease Type 1 von Gierke. What is Liver Disease? How Many People Have Liver Disease? Facts at-a-Glance Also known as von Gierke disease , is a more severe form of Glycogen Storage Disease.

All Glycogen Storage diseases together affect fewer than 1 in 40, persons in the United States. Information for the Newly Diagnosed What are the symptoms of GSD I?

What causes GSD I? How is GSD I diagnosed? How is GSD I treated? Who is at risk for GSD I? Questions to Ask Your Doctor Do I have type 1 or type 2 GSD? When both parents pass the misspelled gene to a child, the child has no normal copy of that gene and therefore develops GSD.

In most cases GSD is diagnosed within the first year of life, but in some cases the diagnosis may not be made until later in childhood. Many different enzymes are used by the body to process glycogen. As a result, there are several types of GSD.

This type of GSD does not cause hypoglycemia. A thorough medical history can also lead the doctor to suspect GSD since it is inherited. Other diagnostic tests may include:. Each type of GSD centers on a certain enzyme or set of enzymes involved in glycogen storage or break down. GSD mostly affects the liver and the muscles, but some types cause problems in other areas of the body as well.

Types of GSD with their alternative names and the parts of the body they affect most include:. GSD types VI and IX can have very mild symptoms and may be underdiagnosed or not diagnosed until adulthood.

Currently, there is no cure for GSD. Treatment will vary depending on what type of GSD your child has; however, the overall goal is to maintain the proper level of glucose in the blood so cells have the fuel they need to prevent long-term complications. Until the early s, children with GSDs had few treatment options and none were very helpful.

Then it was discovered that ingesting uncooked cornstarch regularly throughout the day helped these children maintain a steady, safe glucose level. Cornstarch is a complex carbohydrate that is difficult for the body to digest; therefore it acts as a slow release carbohydrate and maintains normal blood glucose levels for a longer period of time than most carbohydrates in food.

Cornstarch therapy is combined with frequent meals eating every two to four hours of a diet that restricts sucrose table sugar , fructose sugar found in fruits and lactose only for those with GSD I.

Typically, this means no fruit, juice, milk or sweets cookies, cakes, candy, ice cream, etc. because these sugars end up as glycogen trapped in the liver. Infants need to be fed every two hours. Those who are not breastfed must take lactose-free formula.

Red cell aldolase deficiency and hemolytic anemia: a new syndrome. Physicians 86 , — Hurst, J. A syndrome of mental retardation, short stature, hemolytic anemia, delayed puberty, and abnormal facial appearance: similarities to a report of aldolase a deficiency. Miwa, S. Two cases of red cell aldolase deficiency associated with hereditary hemolytic anemia in a Japanese family.

Santoro, L. A new phenotype of aldolase a deficiency in a 14 year-old boy with epilepsy and rhabdomyolysis — case report. Yao, D. Blood , — Papadopoulos, C. Aldolase a deficiency: report of new cases and literature review. Kreuder, J. Brief report: inherited metabolic myopathy and hemolysis due to a mutation in aldolase A.

Mamoune, A. A thermolabile aldolase a mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia. PLoS Genet. Comi, G. Beta-enolase deficiency, a new metabolic myopathy of distal glycolysis. Recurrent rhabdomyolysis due to muscle beta-enolase deficiency: very rare or underestimated?

Wigley, R. The need for biochemical testing in beta-enolase deficiency in the genomic era. Buch, A. Energy metabolism during exercise in patients with beta-enolase deficiency GSDXIII. Moslemi, A. Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.

Tegtmeyer, L. Multiple phenotypes in phosphoglucomutase 1 deficiency. Preisler, N. Impaired glycogen breakdown and synthesis in phosphoglucomutase 1 deficiency. Santer, R. Fanconi-Bickel syndrome-the original patient and his natural history, historical steps leading to the primary defect, and a review of the literature.

Baba, K. A mild clinical phenotype with myopathic and hemolytic forms of phosphoglycerate kinase deficiency PGK Osaka : a case report and literature review. Phosphoglycerate kinase deficiency: a nationwide multicenter retrospective study. Level of residual enzyme activity modulates the phenotype in phosphoglycerate kinase deficiency.

Neurology 91 , e—e Sotiriou, E. Myopathy and parkinsonism in phosphoglycerate kinase deficiency. Muscle Nerve 41 , — Sakaue, S. Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism.

NPJ Parkinsons Dis. Virmani, T. Levodopa responsive parkinsonism in two patients with phosphoglycerate kinase deficiency. Morales-Briceno, H. Parkinsonism in PGK1 deficiency implicates the glycolytic pathway in nigrostriatal dysfunction.

Parkinsonism Relat. Tonin, P. Phosphoglycerate kinase deficiency: biochemical and molecular genetic studies in a new myopathic variant PGK Alberta. Neurology 43 , — Ausems, M. A diagnostic protocol for adult-onset glycogen storage disease type II. Neurology 52 , — Meena, N. Pompe disease: new developments in an old lysosomal storage disorder.

Biomolecules 10 , McAdams, A. Glycogen storage disease, types I to X: criteria for morphologic diagnosis. Maire, I. Biochemical diagnosis of hepatic glycogen storage diseases: 20 years French experience.

Perez, M. Lu, S. Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review. Labrador, E. Glycogen Storage Disease Type VI. Kissel, J. Physiologic assessment of phosphoglycerate mutase deficiency: incremental exercise test.

Neurology 35 , — Tsujino, S. The molecular genetic basis of muscle phosphoglycerate mutase PGAM deficiency. CAS PubMed PubMed Central Google Scholar. Unusual presentation of phosphoglycerate mutase deficiency due to two different mutations in PGAM-M gene.

DiMauro, S. Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy. Science , — Bresolin, N.

Muscle phosphoglycerate mutase PGAM deficiency: a second case. Neurology 33 , — Vita, G. Muscle phosphoglycerate mutase PGAM deficiency in the first Caucasian patient: biochemistry, muscle culture and 31P-MR spectroscopy. Koo, B. Phosphoglycerate mutase deficiency glycogen storage disease X caused by a novel variant in PGAM-M.

Malfatti, E. A new muscle glycogen storage disease associated with glycogenin-1 deficiency. Krag, T. Glycogen synthesis in glycogenin 1-deficient patients: a role for glycogenin 2 in muscle.

Ben Yaou, R. Visuttijai, K. Glycogenin is dispensable for glycogen synthesis in human muscle, and glycogenin deficiency causes polyglucosan storage. Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1.

Cardiomyopathy as presenting sign of glycogenin-1 deficiency-report of three cases and review of the literature. Manz, F. Fanconi—Bickel syndrome. Tarui disease and distal glycogenoses: clinical and genetic update.

Acta Myol. Hamano, T. Phosphoglycerate kinase deficiency: an adult myopathic form with a novel mutation. Neurology 54 , — Rosa, R. A new case of phosphoglycerate kinase deficiency: PGK Creteil associated with rhabdomyolysis and lacking hemolytic anemia.

Blood 60 , 84—91 Phosphoglycerate kinase deficiency: another cause of recurrent myoglobinuria. Pena, L. Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa neoGAA in treatment-naive and alglucosidase alfa-treated patients with late-onset Pompe disease: a phase 1, open-label, multicenter, multinational, ascending dose study.

Radenkovic, S. The metabolic map into the pathomechanism and treatment of PGM1-CDG. Halaby, C. Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring.

Concolino, D. Enzyme replacement therapy: efficacy and limitations. Fukuda, T. Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease. Engineering adeno-associated virus vectors for gene therapy. Kaufmann, K. Gene therapy on the move. EMBO Mol.

Swingle, K. Lipid nanoparticle-mediated delivery of mrna therapeutics and vaccines. Trends Mol. Kowalski, P. Delivering the messenger: advances in technologies for therapeutic mRNA delivery.

Download references. The authors thank T. Krag and M. Sheikh for their work preparing histological images for publication Fig.

Koch for her review of the manuscript and for her contributions to preparing histological images and D. Bali for her thoughtful edits of Table 2. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.

Department of General Paediatrics, Adolescent Medicine and Neonatology, Medical Centre-University of Freiburg, Faculty of Medicine, Freiburg, Germany. Division of Medical Genetics, Department of Paediatrics, Duke University Medical Center, Durham, NC, USA. Copenhagen Neuromuscular Center, Copenhagen University Hospital, Copenhagen, Denmark.

You can also search for this author in PubMed Google Scholar. Introduction W. Authors contributed equally to this work and are listed alphabetically. Correspondence to William B. has received consulting fees from PTC Therapeutics and ReCode Therapeutics. declares that he experiences no competing interests concerning the content of this manuscript.

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Subjects Endocrine system and metabolic diseases Metabolic disorders. Abstract Glycogen storage diseases GSDs are a group of rare, monogenic disorders that share a defect in the synthesis or breakdown of glycogen. Access through your institution.

Buy or subscribe. Change institution. Learn more. References Ferreira, C. Article PubMed PubMed Central Google Scholar Brown, L.

Article CAS PubMed Google Scholar Haring, M. Article PubMed PubMed Central Google Scholar Derks, T. Article CAS PubMed Google Scholar Santalla, A.

Article PubMed PubMed Central Google Scholar Bruno, C. Article PubMed Google Scholar Lucia, A. Article PubMed Google Scholar Herbert, M.

Article PubMed Google Scholar Cho, S. Article CAS PubMed Google Scholar Schreuder, A. Article CAS PubMed Google Scholar Martinez, M. Article PubMed PubMed Central Google Scholar Dashty, M. Article CAS PubMed Google Scholar Adeva-Andany, M. Article PubMed PubMed Central Google Scholar Kanungo, S.

Article CAS PubMed PubMed Central Google Scholar Han, H. Article CAS PubMed PubMed Central Google Scholar Jiang, G. Article CAS PubMed Google Scholar Ruderman, N. Article CAS PubMed Google Scholar Firshman, A. Article CAS PubMed Google Scholar Hedberg-Oldfors, C.

Article CAS Google Scholar Martín, M. Article CAS PubMed Google Scholar Brushia, R. Article CAS PubMed Google Scholar Zhai, L. Article CAS PubMed PubMed Central Google Scholar Van Hoof, F.

Article PubMed Google Scholar Shen, J. Article CAS PubMed PubMed Central Google Scholar Altassan, R. Article CAS PubMed Google Scholar Kishnani, P. Article CAS PubMed Google Scholar Boztug, K. Article CAS PubMed PubMed Central Google Scholar Burchell, A. Article PubMed PubMed Central Google Scholar Zampieri, S.

Article CAS PubMed Google Scholar Kroos, M. Article PubMed Google Scholar Akman, H. Article CAS PubMed Google Scholar Haller, R. Article CAS PubMed Google Scholar Raben, N. Article CAS PubMed Google Scholar Brown, G. Article CAS PubMed Google Scholar Rake, J.

Article PubMed Google Scholar Visser, G. PubMed Google Scholar Koch, R. Article CAS PubMed Google Scholar Richards, S.

Article PubMed PubMed Central Google Scholar Nykamp, K. Article PubMed PubMed Central Google Scholar Kazemi-Esfarjani, P. Article PubMed Google Scholar Sluiter, W. Article CAS PubMed Google Scholar Young, S.

Article PubMed Google Scholar Heiner-Fokkema, M. Article CAS PubMed PubMed Central Google Scholar Paesold-Burda, P. Article CAS PubMed Google Scholar Scalco, R. Article PubMed Google Scholar Lukacs, Z. Article CAS PubMed PubMed Central Google Scholar Topf, A. Article CAS PubMed PubMed Central Google Scholar Kemper, A.

Article PubMed Google Scholar Keutzer, J. Article PubMed PubMed Central Google Scholar Chien, Y. Article PubMed Google Scholar Goomber, S. Article CAS PubMed PubMed Central Google Scholar Prakash, S. Article PubMed Google Scholar Huggins, E. Article CAS PubMed Google Scholar Yoo, H.

Article CAS PubMed Google Scholar Muller, D. Article CAS PubMed Google Scholar Peduto, A. Article CAS PubMed Google Scholar Esquerda, M. Article CAS PubMed Google Scholar Bick, D. Article CAS PubMed Google Scholar Peeks, F.

Article CAS PubMed PubMed Central Google Scholar Rossi, A. Article PubMed PubMed Central Google Scholar Kaiser, N. Article CAS PubMed Google Scholar Lee, P. Article CAS PubMed Google Scholar Franco, L.

Article CAS PubMed Google Scholar Okata, Y. Article PubMed Google Scholar Verbeek, R. Article PubMed Google Scholar Diaz-Manera, J. Article PubMed Google Scholar Vissing, J. Article CAS PubMed Google Scholar Weinstein, D. Article PubMed Google Scholar Amalfitano, A.

CAS PubMed Google Scholar Winkel, L. Article CAS PubMed Google Scholar Klinge, L. Article CAS PubMed Google Scholar Van den Hout, H.

Article PubMed Google Scholar Van den Hout, J. Article PubMed Google Scholar van der Ploeg, A. Article PubMed Google Scholar Strothotte, S. Article CAS PubMed Google Scholar Gungor, D. Article CAS PubMed Google Scholar Dimachkie, M.

Article CAS PubMed PubMed Central Google Scholar Kishnani, P. Article PubMed Google Scholar Dhillon, S. Article CAS PubMed Google Scholar Punnoose, A.

Article CAS PubMed Google Scholar Schoser, B. Article CAS PubMed Google Scholar Blair, H. Article PubMed PubMed Central Google Scholar Banugaria, S. Article CAS PubMed PubMed Central Google Scholar Berrier, K. Article CAS PubMed PubMed Central Google Scholar Patel, T.

Article CAS PubMed Google Scholar Nino, M. Article CAS PubMed PubMed Central Google Scholar Bali, D. Article PubMed Google Scholar Poelman, E. Article CAS PubMed Google Scholar Li, C. Article CAS PubMed PubMed Central Google Scholar Banugaria, S.

Article CAS PubMed Google Scholar Koeberl, D. Article CAS PubMed Google Scholar Veiga-da-Cunha, M. Article CAS PubMed PubMed Central Google Scholar Grünert, S. Article PubMed Google Scholar Grunert, S. Article PubMed PubMed Central Google Scholar Grünert, S. Article PubMed PubMed Central Google Scholar Malatack, J.

Article CAS PubMed PubMed Central Google Scholar Piper, J. Article PubMed Google Scholar Beyzaei, Z. Article PubMed PubMed Central Google Scholar Chan, Y. Article PubMed PubMed Central Google Scholar Yuen, W.

Article CAS Google Scholar Irie, R. Article PubMed Google Scholar Shimizu, S. Article PubMed Google Scholar Troisi, R.

Skip to content. What is Glycoben Glycogen storage disease disease Natural ways to boost your metabolism Glycogen stoeage disease GSD is a Glycogen storage disease metabolic disorder where the body is Glycogen storage disease able to Glycogn store or break down glycogen, a form of sugar or glucose. GSD affects the liver, muscles and other areas of the body, depending on the specific type. The food we eat is broken down into different nutrient components, including glucose. The excess glucose that is not needed right away is stored as glycogen in the liver and muscle cells to use later. When the body needs more energy, enzymes break down glycogen into glucose, a process called glycogen metabolism or glycogenolysis.

Depending on diseaxe type of GSD a Glcyogen has, glycogen Glycogen storage disease build diseas in the liver, in the muscles, or both. GSD can also affect blood cells, the heart, kidneys, diseaase other organs.

Glyogen, glycogen is Glycogne in the Thyroid Supportive Blends until the body needs energy. Then, enzymes storagw glycogen into Sustainable energy support so that it can travel through the bloodstream to cells that need fuel.

Every cell in Glycogen storage disease dissase contains stoarge, but children with GSD lack one Glucogen the enzymes responsible for making glycogen or dusease glycogen to glucose.

Diseaase is atorage rare storae. According to the National Shorage of Diseae DiseasesGlycogen storage disease affects fewer than 1 in 40, people in the United States.

Appetite suppressant effects are many different types of Glyccogen, based on ztorage enzyme is missing. Some types Glycogwn only the liver, others only the muscles, while some Herbal stress management both the liver and the disexse.

Each type has stkrage different symptoms. Treatments vary for the various Gycogen of GSD. Sgorage storage disease type I GSD Ialso known as von Gierke disease, accounts for about 25 percent of all diseasee Glycogen storage disease GSD. Symptoms typically appear when an infant is 3 sforage 4 months diisease age and may include hypoglycemia low blood sugar stkrage, which can cause GlycobenSotrage hunger, and crankiness.

The Time-restricted calorie intake and sometimes Glyclgen kidneys swell due to built-up Glyycogen. Glycogen storage stlrage type III GSD IIIalso known Glycogen storage disease Glycoben disease Glycogen storage disease Forbes Glyocgen, causes glycogen Dsiease build Causes of hypoglycemic unawareness in the Glyocgen and muscles.

Symptoms typically appear within the first year of life. Children Inflammation and memory function this type of GSD may have a swollen atorage, delayed growth Nut-free protein options for athletes, and Glycgoen Glycogen storage disease.

Diswase storage Glycpgen type IV GSD IValso known as Andersen disease, diwease one of diseass most serious types of GSD. This type of GSD often diswase to cirrhosis of the liver and can affect diisease heart and other sorage as well.

Glyckgen with type I LGycogen I Glycogeh have low blood diseease. This type of GSD Natural wound healing also lead to lactic acidosis, a buildup of lactic acid, which can cause painful muscle cramps.

As they mature into adolescence, children with GSD I may have delayed puberty and weak bones osteoporosis. Other risks include:. Infants with type III GSD III may have low blood sugar and excess fat in their blood.

As they get older, their livers may become enlarged. Children with this type of GSD are also at risk for:. Infants with Type IV GSD IV may not have low blood sugar, but they can develop early complications. Children who survive with GSD IV are at risk for the following complications:.

GSD is an inherited disease. Children are born with GSD when both parents have an abnormal gene that gets passed on to one of their children. Children with GSD lack one of the enzymes responsible for making glycogen or converting glycogen to glucose.

As a result, their muscles do not receive the fuel they need to grow and glycogen builds up in their liver and other organs. Diagnosis starts with a health history. The doctor will also do a physical exam and check for signs of an enlarged liver or weak muscles.

The doctor may order blood tests and possibly a liver or muscle biopsy so that samples can be tested for enzyme levels to help determine if a child has GSD. There is currently no cure for GSD.

After diagnosis, children with GSD are usually cared for by several specialists, including specialists in endocrinology and metabolism. Specific dietitians with expertise in this disease should be involved.

Depending on what type of GSD your child has, treatment typically focuses on promoting their growth and development and maintaining a healthy level of glucose in the blood. Typically, doctors recommend small, frequent meals throughout the day.

The meals should be low in sugar to prevent glycogen from building up in the liver. Uncooked cornstarch can help maintain a healthy blood-sugar level. In some cases, doctors may recommend a nasogastric tube or gastrostomy G tube that delivers a continuous supply of nutrition while the child is sleeping.

Children with GSD IV may need a liver transplant if the disease progresses to cirrhosis or liver failure. The Glycogen Storage Diseases Program treats children and adults with known glycogen storage diseases.

Learn more about Glycogen Storage Diseases Program. The Division of Gastroenterology, Hepatology and Nutrition offers care for children with GI, liver, and nutritional problems.

Learn more about Gastroenterology, Hepatology and Nutrition. Breadcrumb Home Conditions Glycogen Storage Disease. What is glycogen storage disease? What are the types of GSD?

The most common types of GSD include: Glycogen storage disease type I GSD Ialso known as von Gierke disease, accounts for about 25 percent of all children with GSD. What are the risks of GSD? Each type of GSD carries specific risks. Other risks include: gout, a type of arthritis adenomas, tumors of the liver that are usually benign non-cancerous inflammatory bowel disease type 1b dental problems recurring infections type 1b pulmonary hypertension Infants with type Glycogej GSD III may have low blood sugar and excess fat in their blood.

Children with this type of GSD are also at risk for: slow growth and short stature muscle weakness Infants with Type IV GSD IV may not have low blood sugar, but Glyocgen can develop early complications. Children who survive with GSD IV are at risk for the following complications: slow weight gain muscle weakness, including a weak heart muscle cirrhosis portal hypertension.

What are the symptoms of glycogen storage disease? Symptoms of GSD typically appear early, when a child is still a baby or very young child. Though symptoms vary depending by type of GSD, the following symptoms are Glycoben delayed growth easy bruising swollen belly weak muscles muscle pain and cramping chronic hunger irritability What causes glycogen storage disease?

How is glycogen storage disease diagnosed? How is glycogen storage disease treated? Programs Glycogen Storage Diseases Program Program The Glycogen Storage Diseases Program treats children and adults with known glycogen storage diseases. Gastroenterology, Hepatology and Nutrition Department The Division of Gastroenterology, Hepatology and Nutrition offers care for children with GI, liver, and nutritional problems.

Contact the Center for Childhood Liver Disease. Request an Appointment Request a Second Opinion.

: Glycogen storage disease

Glycogen storage diseases (glycogenoses) GSD type III Cori's disease, debranching enzyme deficiency GSD type VI Hers' disease, liver glycogen phosphorylase deficiency GSD type V McArdle's disease, myophosphorylase deficiency GSD type IX phosphorylase kinase deficiency Phosphoglucomutase deficiency PGM1-CDG, CDG1T, formerly GSD-XIV. In contrast, it declined by approximately 2. Rake, J. Neonatal Screen. CS every 3—4 h during the day plus extra dose at night. org Fax: What are the symptoms of glycogen storage disease?
Glycogen Storage Disease Metabolic acidosis in Disese critically ill: Glycogen storage disease 1. Toggle limited Glycoen width. Schedule with My Duke Health MyChart. Retrieved November 10, Authority control databases : National Czech Republic. Genetic and Rare Diseases Information Center Glycogen storage disease type 4. Retrieved 23 March
Glycogen Storage Diseases

Therefore, in GSD type I starch is a drug and not just a dietary supplement; it must be given regularly during the day every 3—4 h with a night break not exceeding 7—8 h [ 30 ].

Patients most often need to take an extra dose of starch at night while maintaining a constant supply of carbohydrates in a liquid form, especially during sleep, thus protecting patients with decompensated glycemia from dangerous complications of hypoglycemia.

When intolerance or reluctance to receive RS is observed, either a nasogastric tube or percutaneous endoscopic gastrostomy PEG is required — if the enteral supply is to be maintained for more than 6—8 weeks ESPEGHAN guidelines. The disadvantage of starch is that it is hard to digest — with an infection associated with gastrointestinal irritation in children with glycogenosis there are often problems with starch supplementation.

It is not recommended for patients with type Ib due to their common inflammatory bowel disease and, therefore, additionally impaired absorption.

The formula is used in patients older than 5 years old. Currently, glycosade is to be studied in the United States for its application during the day in adult patients, in whom, due to the slower metabolism than children, the extended-release preparation might be effective not only at night.

According to current US dietary recommendations, the diet should be restricted to simple sugars less than 5—10 g in each meal in all types of GSDs, while it is most restrictive in type I, with RS supplementation in type I every 3—4 h daily plus an extra overnight dose or only 1 night dose in other types [ 64 ].

Because of the increased risk of micronutrient deficiencies vitamin D 3 , calcium-phosphate disturbances, and the risk of osteopenia , multivitamins and vitamin D 3 supplements are also recommended [ 30 , 64 ]. The basic principle of treatment is therefore to limit the simple sugars in a diet rich in complex carbohydrates.

However, the diet is always individually selected for the patient based on its glycemic status, current biochemical findings metabolic equilibrium and anthropometric parameters, and requires close collaboration between the physician, metabolic dietitian, the patient and his family.

Table III summarizes different dietary strategies in ketotic and non-ketotic type I GSDs. Summary of different dietary strategies in ketotic and non-ketotic type I GSDs. As mentioned above, a properly applied specific diet is a treatment in GSDs. It leads not only to stable normoglycemia, but also to decreased hepatomegaly reduction of glycogen storage , improvement of growth and biochemical metabolic control normalization of transaminases, triglycerides, in type I — reduction of lactate and uric acid in blood [ 13 ].

The problem of diet, as an important factor in treatment, may lead to eating disorders in children with GSDs. In the course of metabolic diseases, some eating disorders related strictly to the elimination diet can be observed.

For example, people consuming frequent meals with high carbohydrate content that slows down the release of glucose into the blood may experience a lack of hunger.

Since a lot of attention is paid to eating, it may cause a lack of pleasure from eating a meal, not to mention the lack of taste of non-sweet foods.

As far as children are concerned, following the heavy-starch diet is often associated with digestive problems. Establishing the right diagnosis and setting a proper glycogenic diet will make the patients enjoy eating and discovering new flavors, changing the attitude to a meal as a necessity.

In the treatment of eating disorders, therapies of these disorders adapted to the requirements of GSDs are helpful [ 28 ]. The GSDs, like all genetic diseases, is incurable. Currently, clinical trials on gene therapy for type I glycogenosis clinical phase of GSDI adult safety assessment are ongoing at the Connecticut facility in the US [ 66 ].

Currently, in the USA, the development of adeno-associated virus AAV vector-mediated gene therapy is being carried out for GSD type I based on the success of early-stage clinical trials of gene therapy in hemophilia [ 67 ].

At present, gene therapy for GSD type I is at the stage of a safety clinical trial on adult patients with this type of GSD, and is taking place in the Connecticut Hospital within the GSD program of Prof.

The GSD is a congenital defect of carbohydrate metabolism characterized by hypoglycemia, hepatomegaly, and growth disorders short stature. Basic therapeutic treatment consists in maintaining a proper diet with RS supplementation. Due to the fact that awareness and knowledge about rare diseases are still insufficient, it is important to popularize them among pediatricians, hepatologists and geneticists.

Knowledge of the biochemical basics and glucose metabolism in the human body facilitates proper treatment of GSD. Current issue Archive Manuscripts accepted About the Journal Editorial office Editorial board Abstracting and indexing Subscription Contact Ethical standards and procedures Most read articles Instructions for authors Article Processing Charge APC Regulations of paying article processing charge APC.

Manuscripts accepted. About the Journal Editorial office Editorial board Abstracting and indexing Subscription Contact Ethical standards and procedures Most read articles.

Instructions for authors Article Processing Charge APC Regulations of paying article processing charge APC. Current issue. Hepatic glycogen storage diseases: pathogenesis, clinical symptoms and therapeutic management. Edyta Szymańska 1. Dominika A. Jóźwiak-Dzięcielewska 2.

Joanna Gronek 2. Marta Niewczas 3. Wojciech Czarny 4. Dariusz Rokicki 1. Piotr Gronek 2. Laboratory of Genetics, Department of Gymnastics and Dance, University School of Physical Education, Poznan, Poland.

Department of Sport, Faculty of Physical Education, University of Rzeszow, Rzeszow, Poland. Department of Human Sciences, Faculty of Physical Education, University of Rzeszow, Rzeszow, Poland. Glycogen storage diseases GSDs are genetically determined metabolic diseases that cause disorders of glycogen metabolism in the body.

The first symptoms of the disease usually appear during the first months of life and are thus the domain of pediatricians. Due to the fairly wide access of the authors to unpublished materials and research, as well as direct contact with the GSD patients, the article addresses the problem of actual diagnostic procedures for patients with the suspected diseases.

Knowledge and awareness of the problem among physicians seem insufficient, and research on the diagnosis and treatment of GSD is still ongoing, resulting in a heterogeneous GSD typology and a changing way of its diagnosis and treatment.

Figure 1 Cascade of glycogen breakdown. Glycogen storage diseases glycogenoses Pathophysiology and epidemiology Glycogen storage disease GSD is caused by a genetically determined metabolic block involving enzymes that regulate synthesis glycogenesis or glycogen breakdown glycogenolysis [ 13 ].

Inheritance Glycogen storage diseases, like most metabolic diseases, are inherited in an autosomal recessive AR way. Typology of GSDs It is still an unsettled matter.

Table I Various types of GSDs types of GSDs according to tissue-specific enzymatic deficiency. Table II Classification of GSDs into hepatic and muscle types with separate classification of PhK deficiency type IX. Classic Infantile Juvenile Adult.

Clinical symptoms The basic clinical symptoms common for every type of hepatic GSD are hypoglycemia and hepatomegaly [ 24 ]. Glycogen pathway Decomposition of glycogen molecules is directly related to energy production, and its regulation takes place by activation of the relevant substances and enzymes.

Figure 2 Enzymatic activity of phosphorylase and synthase. Release of glucosephosphate-kinase phosphorylase PhK. Conversion of glucosephosphate to glucosephosphate — phosphoglucomutase. Glucosephosphate metabolism — glucose 6-phosphatasephosphatase 1 G6PC.

The PhK enzyme consists of 4 subunits: α, β, γ, and δ subunits, which are encoded by the following genes: PHKA1 and PHKA2 α1 and α2 subunits expressed in the liver; PHKB subunit β , PHKG1 and PHKG2 subunit γ expressed in the liver [ 34 , 35 ], CALM1, CALM2 and CALM3 subunit δ [ 32 ].

GSD type I Unlike muscles, liver contains the glucosephosphatase membrane enzyme, which removes the phosphate residue to allow the glucose to enter the bloodstream and regulates its concentration [ 52 ]. Dietary management The basic treatment for GSDs is dietary management, which raises many controversies.

Table III Summary of different dietary strategies in ketotic and non-ketotic type I GSDs. CS every 3—4 h during the day plus extra dose at night. Usually only 1 dose of CS at night High-protein diet.

Gene therapy Currently, in the USA, the development of adeno-associated virus AAV vector-mediated gene therapy is being carried out for GSD type I based on the success of early-stage clinical trials of gene therapy in hemophilia [ 67 ].

Conclusions The GSD is a congenital defect of carbohydrate metabolism characterized by hypoglycemia, hepatomegaly, and growth disorders short stature. Conflict of interest The authors declare no conflict of interest. Crystal structure of glycogen debranching enzyme and insights into its catalysis and disease — causing mutations Nat Commun.

Google Scholar. Wang HF , Wu KH , Tsai CL. Neuroglycopenia in an euglycaemic patient under intensive insulin therapy Anaesth Intensive Care. Joung-Hwan J , Streamson CC. The brain — liver connection between BDNF and glucose control Diabetes.

Douillard C , Menton K , Dobbelaere D , Wemeau JL , Saudubray JM , Vantyghem MC. Hypoglycaemia related to inherited metabolic disease in adults Orphanet J Rare Dis.

Moore MC , Katie C , Coate J , et al. Regulation of hepatic glucose uptake and storage in vivo Adv Nutr. Koolman J , Roehm KH. Color Atlas of Biochemistry, 2nd edn. Thieme Stuttgart, New York. Lee PJ , Bhattacharya K. Glycogen Storage Diseases. Oxford University Press, Oxford.

Murray RK , Granner DK , Mayes PA , Rodwell VW. Kneeman JM , Kneeman JM , Misdraji J , Corey KE. Secondary causes of nonalcoholic fatty liver disease Therap Adv Gastroenterol.

Chung ST , Chacko SK , Sunehag AL , Haymond MW. Measurements of gluconeogenesis and glycogenolysis: a methodological review Diabetes. Morris CG , Low J. Metabolic acidosis in the critically ill: part 1. Classification and pathophysiology Anaesthesia. Hochuli M , Christ E , Meienberg F , et al.

Alternative nighttime nutrition regimens in glycogen storage disease type I: a controlled crossover study J Inherit Metab Dis. Wolfsdorf JI , Weinstein DA. Glycogen storage diseases Rev Endocr Metab Disord.

Chou JY , Jun HS , Mansfield BC. Glycogen storage disease type I and G6Pase-beta deficiency: etiology and therapy Nat Rev Endocrinol. Soggia AP , Correa-Giannella ML , Fortes MAH , et al. A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0 BMC Med Genet.

Chial H. Rare genetic disorders: learning about genetic disease through gene mapping, snps, and microarray data Nature Education. Özen H. Glycogen storage diseases: new perspectives World J Gastroenterol. Kim J , Parikh P , Mahboob M , et al. Asymptomatic young man with Danon disease Tex Heart Inst J.

Orho M , Bosshard NU , Buist NR , et al. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0 J Clin Invest. Brown LM , Corrado MM , van der , et al. Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children J Inherit Metab Dis.

Shin YJ. Glycogen storage desease: clinical, biochemical, and molecular heterogeneity Semin Peditar Neurol. Shirazi N , Kalra BP , Bhat NK , et al.

Embryonal hepatoblastoma with co-existent glycogen storage disease in a seven-month-old child J Clin Diagn Res. Esophageal stricture secondary to candidiasis in a child with glycogen storage disease 1b Pediatr Gastroenterol Hepatol Nutr.

Spectrum of AGL mutations in Chinese patients with glycogen storage disease type III: identification of 31 novel mutations J Hum Genet. Raben N , Sherman JB. Mutations in muscle phosphofructokinase gene Hum Mutat.

Fernandes J , Pikaar NA. Hyperlipemia in children with liver glycogen disease Am J Clin Nutr. Hoffmann GF , Smit PA , Schoser B. Glycogen storage diseases of all types J Inherit Metab Dis. Clayton PT. Diagnosis of inherited disorders of liver metabolism J Inherit Metab Dis.

Ketosis in hepatic glycogenosis Arch Dis Child. Kishnani PS , Austin SL , Abdenur JE , et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics.

American College of Medical Genetics and Genomics Genet Med. Kim H , Zheng Z , Walker PD , Kapatos G , Zhang K. CREBH maintains circadian glucose homeostasis by regulating hepatic glycogenolysis and gluconeogenesis Mol Cell Biol. Brushia RJ , Walsh DA. Phosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure Front Biosci.

Hendrickx J , Willems PJ. Genetic deficiences of glycogen phosphorylase system Hum Genet. Burwinkel B , Shiomi S , Al Zaben , et al. Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis Hum Mol Genet.

Burwinkel B , Tanner MS , Kilimann MW. Phosphorylase kinase deficient liver glycogenosis: progression to cirrhosis in infancy associated with PHKG2 mutations HY and LR J Med Genet.

Francke U , Darras TB , Zander NF , Kilimann MW. Assignment of human genes for phosphorylase kinase subunits alpha PHKA to Xqq13 and beta PHKB to 16qq13 Am J Hum Genet.

PHKA2 mutation spectrum in Korean patients with glycogen storage disease type IX: prevalence of deletion mutations BMC Med Genet. Carrière C , Jonic S , Mornon JP , et al. Tsilianidis LA , Fiske LM , Siegel S , et al. Aggressive therapy improves cirrhosis in glycogen storage disease type IX Mol Genet Metab.

Bali DS , Goldstein JL , Fredrickson K , et al. Variability of disease spectrum in children with liver phosphorylase kinase deficiency caused by mutations in the PHKG2 gene Mol Genet Metab.

Davit-Spraul A , Piraud M , Dobbelaere D , et al. Liver glycogen storage diseases due to phosphorylase system deficiencies: diagnosis thanks to non-invasive blood enzymatic and molecular studies Mol Genet Metab.

Kagalwalla AF , Kagalwalla YA , Al Ajaj , et al. Phosphorylase b kinase deficiency glycogenosis with cirrhosis of the liver J Pediatr. Moses SW , Parvari R. The variable presentations of glycogen storage disease type IV: a review of clinical, enzymatic and molecular studies Curr Mol Med.

Rudolfová J , Slovácková R , Trbusek M , et al. Identification of three novel mutations in the PHKA2 gene in Czech patients with X-linked liver glycogenosis J Inherit Metab Dis.

Shen JJ , Chen YT. Molecular characterization of glycogen storage disease type III Curr Mol Med. Lucchiari S , Fogh I , Prelle A , et al.

Clinical and genetic variability of glycogen storage disease type IIIa: seven novel AGL gene mutations in the Mediterranean area Am J Med Genet. Demo E , Frush D , Gottfried M , et al. Glycogen storage disease type III-hepatocellular carcinoma a long-term complication?

J Hepatol. Dagli AI , Weinstein DA , Adam MP , Ardinger HH , Pagon RA , et al. GeneReviews® [Internet]. University of Washington, Seattle, Seattle WA. Roscher A , Patel J , Hewson S , et al. The natural history of glycogen storage disease types VI and IX: long-term outcome from the largest metabolic center in Canada Mol Genet Metab.

Magoulas PL , El-Hattab AW , Adam MP , Ardinger HH , Pagon RA , et al. Paradas C , Akman HO , Ionete C , et al. Branching enzyme deficiency: expanding the clinical spectrum JAMA Neurol.

Epub Jun 3. Neuromuscular Disorders. A case of myopathy associated with a dystrophin gene deletion and abnormal glycogen storage. Muscle Nerve. February Pediatric Neurology. Acta Myologica. Annals of Indian Academy of Neurology.

Practical Neurology. Retrieved May 24, MedLink Neurology. Biochemical Journal. April Clinical Physiology. Journal of Thyroid Research. Living With McArdle Disease PDF. IamGSD Internation Association for Muscle Glycogen Storage Disease. Orphanet Journal of Rare Diseases. Molecular Genetics and Metabolism Reports.

Frontiers in Neurology. North American Journal of Medical Sciences. Frontiers in Physiology. ISSN X. June Endocrinologia Japonica. Journal of Cachexia, Sarcopenia and Muscle. Journal of Pediatric Neurosciences. Journal of the Neurological Sciences.

Brain: A Journal of Neurology. Human Mutation. NORD National Organization for Rare Disorders. Retrieved 23 March British Journal of Sports Medicine. Journal of Inborn Errors of Metabolism and Screening. Classification D. ICD - 10 : E Inborn error of carbohydrate metabolism : monosaccharide metabolism disorders Including glycogen storage diseases GSD.

Congenital alactasia Sucrose intolerance. Glucose-galactose malabsorption Inborn errors of renal tubular transport Renal glycosuria Fructose malabsorption De Vivo Disease GLUT1 deficiency Fanconi-Bickel syndrome GLUT2 deficiency. Essential fructosuria Fructose intolerance.

GSD type 0 glycogen synthase deficiency GSD type IV Andersen's disease, branching enzyme deficiency Adult polyglucosan body disease APBD Lafora disease GSD type XV glycogenin deficiency. GSD type III Cori's disease, debranching enzyme deficiency GSD type VI Hers' disease, liver glycogen phosphorylase deficiency GSD type V McArdle's disease, myophosphorylase deficiency GSD type IX phosphorylase kinase deficiency Phosphoglucomutase deficiency PGM1-CDG, CDG1T, formerly GSD-XIV.

Glycogen storage disease type II Pompe's disease, glucosidase deficiency, formerly GSD-IIa Danon disease LAMP2 deficiency, formerly GSD-IIb. Pyruvate carboxylase deficiency Fructose bisphosphatase deficiency GSD type I von Gierke's disease, glucose 6-phosphatase deficiency.

Glucosephosphate dehydrogenase deficiency Transaldolase deficiency SDDHD Transketolase deficiency 6-phosphogluconate dehydrogenase deficiency.

Hyperoxaluria Primary hyperoxaluria Pentosuria Fatal congenital nonlysosomal cardiac glycogenosis AMP-activated protein kinase deficiency, PRKAG2.

Authority control databases : National Japan. Diseases of muscle , neuromuscular junction , and neuromuscular disease. autoimmune Myasthenia gravis Lambert—Eaton myasthenic syndrome Neuromyotonia Congenital myasthenic syndrome.

Limb-girdle muscular dystrophy 1 Oculopharyngeal Facioscapulohumeral Myotonic Distal most. Calpainopathy Limb-girdle muscular dystrophy 2 Congenital Fukuyama Ullrich Walker—Warburg. dystrophin Becker's Duchenne Emery—Dreifuss. collagen disease Bethlem myopathy PTP disease X-linked MTM adaptor protein disease BIN1-linked centronuclear myopathy cytoskeleton disease Nemaline myopathy Zaspopathy.

Myotonia congenita Thomsen disease Becker disease Neuromyotonia Isaacs syndrome Paramyotonia congenita. Hypokalemic Thyrotoxic Hyperkalemic. Central core disease. Brody disease ATP2A1. Muscle Glycogen storage disease Fatty-acid metabolism disorder AMPD1 deficiency Mitochondrial myopathy MELAS MERRF KSS PEO.

Hypothyroid myopathy Kocher—Debre—Semelaigne syndrome Hoffmann syndrome Hyperthyroid myopathy Thyrotoxic myopathy Hypoparathyroid myopathy Hyperparathyroid myopathy Hypercortisolism Corticosteroid myopathy Testosterone deficiency myopathy Late-onset hypogonadism Hypogonadotropic hypogonadism Androgen deficiency.

Inflammatory myopathy Congenital myopathy. Symptoms and conditions relating to muscle. Myalgia Fibromyalgia Acute Delayed onset. Myositis Pyomyositis Myoedema Hypothyroid myopathy. Categories : Inborn errors of carbohydrate metabolism Hepatology Rare diseases Diseases of liver Muscular disorders Metabolic disorders.

Hidden categories: CS1 errors: missing periodical CS1 errors: periodical ignored Articles with short description Short description is different from Wikidata All articles with unsourced statements Articles with unsourced statements from December Articles with NDL identifiers.

Toggle limited content width. GSD 0 Lewis' disease [5]. Muscle 0b Glycogen deficiency in muscle fibres.

Type I muscle fibre predominance. Exercise-induced, muscle fatigue, myalgia, fainting. Liver 0a Growth failure in some cases.

Liver 0a Epilepsy [9] Muscle 0b Rarely epilepsy, tonic-clonic seizures. Lactic acidosis , hyperuricemia. Acid alpha-glucosidase GAA Lysosome-associated membrane protein 2 LAMP2. Pompe disease is 1 in 13, Muscle weakness , exercise intolerance , abnormal lysosomal glycogen accumulation in muscle biopsy.

Late-onset Pompe may have a pseudoathletic appearance of hypertrophic calf muscles. Progressive proximal skeletal muscle weakness with varied timeline to threshold of functional limitation early childhood to adulthood. Heart failure infantile , respiratory difficulty due to muscle weakness. Glycogen debranching enzyme AGL.

May have a pseudoathletic appearance of hypertrophic muscles. Failure to thrive [17]. Glycogen branching enzyme GBE1. Failure to thrive , death at age ~5 years. Muscle glycogen phosphorylase PYGM.

Exercise-induced muscle fatigue and cramps. Rhabdomyolysis possible. May have a pseudoathletic appearance of hypertrophic calf muscles.

Renal failure by myoglobinuria , second wind phenomenon , inappropriate rapid heart rate sinus tachycardia response to exercise, myogenic hyperuricemia [18].

Liver glycogen phosphorylase PYGL. Muscle phosphofructokinase PFKM. developmental delay. In some haemolytic anaemia , myogenic hyperuricemia [18].

IXd Exercise-induced muscle cramps, stiffness, weakness fatigue , and pain. Liver type: Delayed motor development , Developmental delay. Muscle Phosphoglycerate mutase PGAM2.

Exercise-induced muscle cramps and weakness [26]. Myoglobinuria [27]. Muscle lactate dehydrogenase LDHA. Glucose transporter GLUT2. Aldolase A ALDOA. Exercise intolerance , cramps. In some Rhabdomyolysis. Hemolytic anemia and other symptoms.

β-enolase ENO3. Increasing intensity of myalgias over decades [29]. Serum CK : Episodic elevations; Reduced with rest [29]. Phosphoglucomutase-1 PGM1. Two forms: exclusively myopathic and multi-system including muscles. Short stature, some have developmental delay, and rarely delayed puberty.

Highly variable phenotype and severity. Commonly elevated serum CK, abnormal serum transferrin loss of complete N-glycans , short stature, cleft palate, bifid uvula, and hepatopathy.

Glycogenin-1 GYG1. Rare [33]. Arrhythmia, biopsy of heart showed abnormal glycogen deposits different from polyglucosan bodies in cardiomyocytes.

Storqge updated: December 23, Atorage published:Glycogen storage disease,, Glyxogen,HbAc analysis NORD gratefully acknowledges Deeksha Bali, PhD, Professor, Division of Medical genetics, Department Glycogen storage disease Pediatrics, Duke Glycogen storage disease Co-Director, Xisease Genetics Laboratories, Duke University Health System, and Digestive aid formula Chen, MD, Glycogen storage disease, Professor, Division of Medical Storaage, Department of Pediatrics, Duke Medicine; Distinguished Research Fellow, Academia Sinica Institute of Biomedical Sciences, Taiwan for assistance in the preparation of this report. Glycogen storage diseases are a group of disorders in which stored glycogen cannot be metabolized into glucose to supply energy and to maintain steady blood glucose levels for the body. Type I glycogen storage disease is inherited as an autosomal recessive genetic disorder. Glycogen storage disease type I GSDI is characterized by accumulation of excessive glycogen and fat in the liver and kidneys that can result in an enlarged liver and kidneys and growth retardation leading to short stature. GSDI is associated with abnormalities mutations in the G6PC gene GSDIA or SLC37A4 gene GSDIB. Glycogen storage disease

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