We want to hear from you. [msdmanuals.com], Neonatal Cardiac PR interval: Short Congestive heart failure Cardiomyopathy: Vacuolar; Cardiomegaly, Biventricular hypertrophy Glycogen: Increased in myocardium Phosphorylase kinase activity: Absent in myocardium Respiratory Failure Pulmonary edema Macroglossia [orpha.net], […] into alternative pathways resulting in 3 major metabolic consequences: [2] Hyperlacticacidemia, which develops as a byproduct of enhanced glycolysis Hyperuricemia, which arises due to shunting of glucose-6-phosphate into the pentose phosphate pathway Hypertriglyceridemia Symptoms … The liver and the skeletal muscles are sites where glycogen can be stored, but in the setting of various GSDs, enzymes that are involved in its creation from glucose are deficient. is updated regularly. Have a question? Do you have updated information on this disease? [ghr.nlm.nih.gov], High lipid levels can lead to the formation of fatty skin growths called xanthomas. These include Types 0, I, III, VI, and IX. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. Consequently, intralysosomal accumulation of glycogen occurs and causes a severe clinical presentation consisting of cardiac and, Type III (known as either Forbes of Cori disease) is characterized by glycogen debranching enzyme deficiency, which is essential for glycogen degradation from the liver and muscles. Glycogen is converted from glucose in liver and skeletal muscles to some extent and these two organs are principally affected [1]. The molecular basis of type 1 glycogen storage diseases. Glycogen storage disease type III (also known as GSDIII or Cori disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. Some GSDs, such as types V and VI… [emedicine.medscape.com], Diagnostic methods Diagnosis is based on clinical presentation, and glycemia and lactacidemia levels, after a meal (hyperglycemia and hypolactacidemia), and after three to four hour fasting (hypoglycemia and hyperlactacidemia). New York, NY: McGraw-Hill; 2012. May 21, 2020. They can direct you to research, resources, and services. Many patients, however, suffer a poor prognosis, as several subtypes can be fatal within years due to heart or liver failure, which is why early recognition of this disease is imperative in prolonging survival rates. The HPO Symptoms of the following disorders can be similar to those of glycogen storage disease type IX. Glycogen storage disease type 2 signs and symptoms. It is passed down from parents to children (inherited). Some GSDs affect mostly the liver. Glycogen storage disease type 7 (GSD7), also called muscle phosphofructokinase deficiency or Tarui's disease, is a rare inherited disease, caused by homozygous or compound heterozygous mutation in the PFKM gene.… Glycogen Storage Disease Type 7: Read more about Symptoms… The Association for Glycogen Storage Disease - AGSD - was established in 1979 in order to create an organization which would be a focus for parents of and individuals with glycogen storage disease … Genetics in Medicine. Although there are several types of GSD, this article focuses on glycogen storage disease, Type 1a, which is the most common type of GSD. expand submenu for Find Diseases By Category, expand submenu for Patients, Families and Friends, expand submenu for Healthcare Professionals. We remove all identifying information when posting a question to protect your privacy. The iron-storage pigment in tissues is called hemosiderin because it was believed to be ... and genetic factors interact to cause disease. Forbes Disease belongs to the family of glycogen storage disorders and is inherited as an autosomal recessive disorder. Glycogen storage disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. Type II (Pompe disease) is estimated to develop in 1 per 40,000 births, whereas type III occurs in approximately 1 per 5,400 births, with a significant predilection toward Sephadric Jews of North Africa [4] [5]. heart failure Arrhythmia Variant with no cardiac involvement: Longer survival Liver involvement Pulmonary: Pneumonia Motor Hypotonia (88%) Respiratory distress (80%) Weakness (60%) Anesthesia 18 Succinylcholine: Increased risk Arrhythmia Hyperkalemia [ncbi.nlm.nih.gov], At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. 3 Glycogen storage disease type II – Pompe disease. Symptoms of the following disorders can be similar to those of glycogen storage disease type I. For some GSDs, moderate exercise, vitamin supplementation and appropriate dietary changes are only options. For most GSDs, each … [online.epocrates.com], The lipid abnormalities, which include hypercholesterolemia (decreased high-density lipoprotein [HDL] cholesterol and increased low-density lipoprotein [LDL] cholesterol), together with the characteristic hypertriglyceridemia do not cause premature atherosclerotic Making the diagnosis of GSD may be difficult, but patients with progressive liver disease and/or muscle cramping, fatigue and poor general condition without an identifiable cause, a high suspicion to one of the GSDs should be present. Glycogen storage diseases are caused by the lack of an enzyme needed to change glucose into glycogen and break down glycogen into glucose. Type VII (Tarui disease) is most commonly seen in Ashkenazi Jews and the Japanese. Hypoglycemia, hyperlipidemia and growth retardation are commonly observed, but some symptoms are specific for certain subtypes, such as elevated blood lactate (type I), profound neutropenia (type Ib), ketosis (types VI and 0) and cardiomyopathy (type II). Questions sent to GARD may be posted here if the information could be helpful to others. Glycogen is synthesized when excess concentrations of glucose are introduced through food, but the body can store limited amounts of glycogen. Patients with the classic infantile form of Pompe disease are the most severely affected. There are four symptoms that might cause the doctor to suspect a type of GSD that affects the liver. In general, the prognosis of GSDs range from mild to severe and rapidly fatal across different subtypes [8], but early recognition of the disease may prevent complications such as hepatic, respiratory and cardiac failure, which will invariably prolong the patient's life. If your child's doctor suspects a glycogen storage diseases, he or she will ask about your child's symptoms … All of these enzymes are deficient in certain types of GSDs, with the common end-result being inability of the liver and muscles to degrade glycogen and provide the necessary energy for metabolic functions, which manifests in a variety of symptoms, depending on the subtype and the severity of enzyme deficiency. Symptoms of Glycogen storage diseases: Introduction. [nature.com], Although none of seven surviving female family members (14 to 46 years of age) with LAMP2 mutations had cardiac symptoms or abnormal cardiac studies, one woman (Family Member CZ I-2) died from congestive heart failure at the age of 44. Comparisons may be useful for a differential diagnosis. Chou JY. Philadelphia, PA: Elsevier Saunders; 2013. 2016; Feb 25 [Epub ahead of print]. Harrison's Principles of Internal Medicine, 18e. We also encourage you to explore the rest of this page to find resources that can help you find specialists. You can help advance Symptoms and complications vary depending on the specific type of glycogen storage disease. It is unclear how tubular aggregates are associated with the signs and symptoms … There are numerous forms of glycogen storage diseases, but the common end-result is inability to store glycogen in either the liver and/or muscles due to enzyme deficiencies that are transmitted by an autosomal recessive pattern of inheritance. Symptoms of low blood glucose, or hypoglycemia, include sweating, tremor, drowsiness, confusion, and, sometimes, seizures. Making the diagnosis may be quite difficult, but liver or skeletal muscle symptoms together with hypoglycemia that do not have an identifiable cause should rise suspicion toward GSDs. Association for Glycogen Storage Disease UK (AGSD-UK). They may be able to refer you to someone they know through conferences or research efforts. Typical symptoms … For these reasons, it is important to identify the exact subtype in order to instate appropriate therapy and prevent further complications. The accumulation of glycogen … Glycogen storage disease type I (GSD I), also known as von Gierke disease, accounts for about 25 percent of all children with GSD. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. Symptoms vary based on the type of GSD.  Hyperuricemia:  Glucose 6-phosphate that accumulates is diverted to HMP Shunt, leading to increased synthesis of ribose If you do not want your question posted, please let us know. Glycogen storage diseases (GSDs) result in impaired utilization of glycogen as a result of various enzyme deficiencies. 19th Edition. Please note that the table may not include all the possible conditions related to this disease. Today, more than 20 glycogen storage diseases (GSDs) are described in literature and they all cause the same metabolic disturbance - disruption of normal glycogen storage and inability of the body to utilize this source of energy for its needs. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. How are types of glycogen storage diseases (GSDs) detected? Ninth edition. The types and severity of symptoms of glycogen storage diseases vary between individuals and differ based on the specific type of glycogen storage disease. Enzyme deficiencies are acquired through autosomal recessive pattern of inheritance in virtually all types, but rare cases (type IX) have shown to occur as a result of X-linked transmission [8]. Inclusion on this list is not an endorsement by GARD. Use the HPO ID to access more in-depth information about a symptom. Deficiency of phosphofructokinase is the main pathological mechanism [8]. Online Mendelian Inheritance in Man (OMIM), Rare Diseases Are Not Rare - Gallery of Creative Work Raises Awareness of Rare Diseases, NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community, NCATS Translational Approach Addresses COVID-19. The report in 1984 first suggested that serial echocardiograms might be able to identify individuals with GSD III who have cardiac involvement and are at risk of symptomatic, Although none of seven surviving female family members (14 to 46 years of age) with LAMP2 mutations had cardiac symptoms or abnormal cardiac studies, one woman (Family Member CZ I-2) died from, Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe. Type Ib patients may develop recurrent infections that can be fatal due to persistent neutropenia, while Pompe disease is often fatal during childhood due to respiratory and cardiac failure [4] [13]. Changes in dietary habits through introduction of uncooked cornstarch is a very useful method to recover from persistent low sugar levels, whereas symptomatic therapy and even use of recombinant human enzymes has been accomplished in some subtypes. Acta Myologica. Aster, JC, Abbas, AK, Robbins, SL1, Kumar, V. Robbins basic pathology. 2001;1(1):25-44. It accounts for about 90% of all types of GSD. The gold standard, however, is either biopsy or detection of reduced enzymatic activity in the target tissue, while magnetic resonance imaging (MRI) can provide important clues as well [11]. Because many symptoms … Do you know of a review article?  There is a blockade in gluconeogenesis. A health care provider may consider these conditions in the table below when making a diagnosis. Maintenance of blood glucose through introduction of corn starch is highly effective for type III and type I, although fructose and galactose intake should be limited for type I patients. [orpha.net], Phenotype and clinics Patients have poor tolerance to fasting (with hypoglycemia and hyperlactacidemia after 3 to 4 hours of fasting), marked hepatomegaly, full-cheeked round face, growth retardation (small stature and delayed puberty), generally improved Merck Manual of Diagnosis and Therapy. Manzia TM, Angelico R, Toti L, Cillis A, Ciano P, Orlando G, Anselmo A, Angelico M, Tisone G. Glycogen storage disease type Ia and VI associated with. The enzyme defect results in severe fasting hypoglycemia, In fact, consuming carbohydrates exacerbates exercise intolerance because, Management of type I depends on symptomatic therapy and dietary changes that comprise introduction of raw, uncooked cornstarch, which is profoundly effective in correcting, Adequate dietary management of hypoglycemia is sufficient for the majority of patients, Treatment of type IV (Andersen disease) GSD relies on palliative care, since a, Type II (Pompe disease) develops as a result of acid alpha-glucosidase deficiency, a glycogen-degrading lysosomal enzyme, for which it is often classified into the group of lysosomal storage diseases (LSDs) [4]. On the other hand, enzyme supplementation has been introduced to patients suffering from type II GSD and has markedly improved patient outcomes [4]. If you have problems viewing PDF files, download the latest version of Adobe Reader, For language access assistance, contact the NCATS Public Information Officer, Genetic and Rare Diseases Information Center (GARD) - PO Box 8126, Gaithersburg, MD 20898-8126 - Toll-free: 1-888-205-2311, In infancy, individuals with glycogen storage disease type 3 (GSDIII) may have, Mild and nonprogressive mental retardation, Elevated circulating creatine phosphokinase, Glycogen storage disease type 3 (GSDIII) is caused by changes (, Glycogen storage disease type 3 (GSDIII) is, Glycogen storage disease type 3 (GSDIII) should be suspected when three main features are present: hepatomegaly (enlarged liver), ketotic, There is not currently a cure for for glycogen storage disease type 3 (GSDIII). Although hardly any symptoms may be apparent at birth, the disease … Semin Hematol. If you can’t find a specialist in your local area, try contacting national or international specialists. An enlarged liver is linked to low blood glucose levels because excess glycogen is stored in the liver instead of being released as glucose in the blood stream. Welcome! Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Kishnani PS, Austin SL, Arn P, Bali DS, Boney A, Case LE, et al. They develop cirrhosis of the liver by age 3-5. [atlasgeneticsoncology.org], The enzyme defect results in severe fasting hypoglycemia, hyperlactacidemia, hyperuricemia, and hyperlipidemia. The prognosis of patients with GSDs significantly depend on the subtype. These include: A low blood glucose … This means that the disease is present only if both parent transfer have a defective gene copy and transfer it to their child, whereas only one transferred copy implies that the child is a carrier but does not develop any symptoms. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011. For all diseases, the exact enzyme deficiencies have been identified. Some types (I and VI) have been associated with hepatocellular carcinoma [14]. Forbes disease; Cori disease; Limit dextrinosis; Forbes disease; Cori disease; Limit dextrinosis; Amylo-1,6-glucosidase deficiency; Glycogen debrancher deficiency, placeholder for the horizontal scroll slider, Office of Rare Disease Research Facebook Page, Office of Rare Disease Research on Twitter, U.S. Department of Health & Human Services, Caring for Your Patient with a Rare Disease, Preguntas Más Frecuentes Sobre Enfermedades Raras, Como Encontrar un Especialista en su Enfermedad, Consejos Para una Condición no Diagnosticada, Consejos Para Obtener Ayuda Financiera Para Una Enfermedad, Preguntas Más Frecuentes Sobre los Trastornos Cromosómicos, Human Phenotype Ontology Rapid liver failure that necessitates transplantation is seen in type IV patients, whereas a mild and relatively benign clinical course may be observed in type III and type VI [8]. A definite diagnosis can be made by either biopsy or genetic testing for deficient enzymes. (HPO) . Glycogen storage disease is a rare, inherited metabolic disease … Contact a GARD Information Specialist. This table lists symptoms that people with this disease may have. Symptoms may become evident after about five to seven months of age, but the disorder more commonly manifests within the womb, causing stillbirth or death soon after birth, primarily from hypoglycemia. Typical symptoms include weakness, sweating, confusion, … On the other hand, some subtypes have shown to be extremely rare, like type XI and 0, as only a handful of cases described in literature [9] [10]. Glycogen storage disease (GSD) is a rare genetic disorder that affects about one in 20,000 people in the U.S.[*].People with GSD have trouble synthesizing and breaking down glucose, which can cause a … rare disease research! [emedicine.medscape.com], […] be produced by glomerular hyperfiltration, TGF-beta expression which is induced by renin-angiotensin-aldosterone system (RAS) and uric acid, and the increase in both small dense LDL and modified LDL which is characteristic of GSD Iota(a) as well as hypertriglyceridemia Because of its role in energy production and utilization by many tissues, numerous symptoms may be encountered. The in-depth resources contain medical and scientific language that may be hard to understand. [slideshare.net], Affected individuals may also have diarrhea and deposits of cholesterol in the skin (xanthomas). We want to hear from you. These types (except for GSD type 0) may cause the liver to become enlarged. Glycogen storage disease (GSD) is a rare condition that changes the way the body uses and stores glycogen, a form of sugar. Clinical presentation somewhat depends on the type of GSD and a broad classification into liver and muscle glycogenoses aids the physician in differentiating between various forms [8]. Santer R, Steinmann B, Schaub J. Fanconi-Bickel syndrome--a. Weinstein DA, Correia CE, Saunders AC, Wolfsdorf JI. Glycogen storage disease type II (acid maltase deficiency, or Pompe disease) (OMIM 232300) is caused by a deficiency of α-1,4 glucosidase, an enzyme required for the degradation of lysosomal glycogen … People with GSDI may experience delayed puberty. Children's Fund for Glycogen Storage Disease Research, Inc. International Association for Muscle Glycogen Storage Disease (IamGSD), https://www.metabolicsupportuk.org/contact-us. We want to hear from you. [ncbi.nlm.nih.gov], Most affected individuals exhibit resolution of hepatomegaly, hypotonia, muscle weakness, risk of fasting hypoglycemia, and abnormal biochemical parameters before or at puberty. Porter RS, Kaplan JL. 2008;5(4):569-578. Treatment principles depend on the subtype. Online directories are provided by the. http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii, http://www.ncbi.nlm.nih.gov/books/NBK26372/, http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=366, http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/396/viewAbstract, http://emedicine.medscape.com/article/119597-treatment. Although exact enzyme deficiencies have been determined in virtually all subtypes, prevention of GSDs is currently not possible, as the triggers that are responsible for their development are unknown. Treatment depends on the subtype [8]. Symptoms may appear at any age, but peak in childhood, adulthood and mid-adolescence. If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. (HPO). Learn the symptoms. May 22, 2020, NCATS Translational Approach Addresses COVID-19 [ncbi.nlm.nih.gov],  Excess of acetyl CoA resulting in increased cholesterol levels, produce xanthomas. Consequently, impaired glycogen conversion to glucose leads to very low glucose levels (hypoglycemia), one of the most important manifestations of this group of diseases. December 1, 2020, Rare Diseases Are Not Rare - Gallery of Creative Work Raises Awareness of Rare Diseases Glucose-6-phosphatase (type I), acid alpha-glucosidase (type II), glycogen debranching enzyme (type III), glycogen branching enzyme (type IV), glycogen phosphorylase (type V), liver phosphorylase (type IV), phosphofructokinase (type VII), liver phosphorylase kinase (type IX) GLUT2 (type XI), glycogen synthase (type 0) and several other enzyme deficiencies have been established. Glycogen storage diseases are caused by the lack of an enzyme needed to change glucose into glycogen and break down glycogen into glucose. [rarediseases.org]. GSDs roughly develop in approximately 1 per 25,000 individuals and gender distribution is mostly equal. Glycogen storage disease type I (also known as GSDI or von Gierke disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. In some cases, diet therapy is helpful. Treatment principles almost strictly depend on the type of GSD: Management of hypoglycemia through dietary changes and additional symptoms is imperative for other GSDs, but in general, this approach is favored across all subtypes so that the metabolic needs for glycogen and energy are fulfilled. Enzyme deficiency that impairs normal glycogen degradation is the principal cause of all GSDs (except in type 0, where glycogen synthase deficiency results in impaired glycogen storage in the liver) [10]. Enzyme deficiencies occur as a result of genetic mutations that are transferred from parent to their child through an autosomal recessive pattern of inheritance. [ncbi.nlm.nih.gov], We report a 25-year-old man with glycogenosis III who presented with a progressive 2 year history of fatigue, hand stiffness and cramping. Detailed evaluations may be useful for a differential diagnosis: Forbes or Cori disease (GSD-III) is one of several glycogen storage … Get the latest research information from NIH: https://www.nih.gov/coronavirus (link is external). Various enzymes are involved in its breakdown and conversion to glucose, including debranching enzyme, liver and muscle phosphorylase kinases, acid maltase, phosphofructokinase, glucose-6-phosphatase and GLUT2 transporter [11]. The HPO collects information on symptoms that have been described in medical resources. 2014;(11):CD003458. Curr Mol Med. For most diseases, symptoms will vary from person to person. 5. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder … This information comes from a database called the Human Phenotype Ontology Glycogen storage disease IV causes cirrhosis; it may also cause heart or muscle dysfunction. 2002;39(2):103-106. [ncbi.nlm.nih.gov], Biological findings include hypoglycemia without acidosis, hypertriglyceridemia, and hypertransaminasemia during childhood. Typical symptoms include weakness, sweating, confusion, … The management of glycemic control remains a clinical challenge, requiring management of both fasting hypoglycemia from glycogen storage disease, as well as post-prandial hyperglycemia from diabetes mellitus. Type IX GSD, unlike all other forms, is transmitted both by. NORD RareLaunch® Workshops Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care. This impairment disrupts the liver's ability to break down stored glycogen that is necessary to maintain adequate blood sugar levels. Up to today, 23 GSDs have been established [2], and are classified into [1-15]: Although each type is distinguished by deficiency of different enzymes, signs and symptoms that reflect hepatic and skeletal pathology without an evident cause can rise clinical suspicion. Neurotherapeutics. Glycogen storage disease type 5 commonly presents with exercise … Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing. Andreu A, Nogales-Gadea G, Cassandrini D, Arenas J, Bruno C. McArdle disease: molecular genetic update. The common features, particularly for type I, include: Abnormally slow growth which may be … […] glucose transporter Probably same as Ic GSD II (Pompe disease, 232300) Onset: Infancy, childhood, or adulthood; residual enzyme activity in child and adult forms Clinical features: In infantile form, cardiomyopathy with heart failure, severe hypotonia, Neonatal Cardiac PR interval: Short Congestive heart failure Cardiomyopathy: Vacuolar; Cardiomegaly, Biventricular hypertrophy Glycogen: Increased in myocardium Phosphorylase kinase activity: Absent in myocardium Respiratory Failure Pulmonary edema, GSD should be suspected in a child with unexplained. Treatment of Glycogen Storage Disease … Too much sugar builds up and damages your muscles and organs. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. The initial diagnosis can be made by clinical criteria, whereas confirmation can be determined by genetic testing that may reveal mutated genes that led to enzyme deficiencies. [ceaccp.oxfordjournals.org], […] glucose transporter Probably same as Ic GSD II (Pompe disease, 232300) Onset: Infancy, childhood, or adulthood; residual enzyme activity in child and adult forms Clinical features: In infantile form, cardiomyopathy with heart failure, severe hypotonia, macroglossia [doi.org]. Type I Glycogen Storage Disease accounts for about 25% of all cases of GSD diagnosed in the USA and in Europe and has an estimated incidence of about 1 in 100,000 live births.
2020 glycogen storage disease symptoms