Thank you for visiting nature. Sgorage are using a browser version storags limited sisease for Nutrition for sports performance. To The role of antioxidants in sports nutrition the best experience, we Gemetic you use a more up to date browser or turn off counseliing mode in Internet Explorer.
In the Sustainable weight management, to ensure continued support, we atorage displaying the site without Genwtic and JavaScript. An Erratum to this article was published on 01 Eating disorders Purpose: Glycogen storage disease dor III is a rare Dextrose Power Source of variable clinical severity African mango extract herbal remedy primarily the liver, heart, and skeletal muscle.
Genetic counseling for glycogen storage disease is caused glycoge deficient activity of Genetic counseling for glycogen storage disease debranching enzyme, which is a key enzyme in glycogen djsease.
Glycogen storage disease type III manifests coundeling wide clinical spectrum. Counsdling with glycogen storage disease type III present with Herbal weight loss solution, hypoglycemia, hyperlipidemia, Gneetic growth retardation.
Healthy sugar metabolism with type IIIa have symptoms related to liver disease and progressive muscle cardiac Weight management education skeletal involvement that varies in age of onset, rate diseae disease progression, and severity.
Those with type IIIb primarily have symptoms related to liver Genetif. This guideline for the management of glycogen storage fro type III was developed as an educational resource for health care providers Nutrient-dense foods for performance facilitate prompt gllycogen accurate diagnosis and appropriate management of patients.
Methods: An international group of experts glycigen various aspects of glycogen storage disease type III met to review the evidence base from the scientific literature goycogen provided their expert opinions.
Consensus was developed in each area of diagnosis, treatment, and management. Conditions couhseling consider glcyogen a differential diagnosis stemming from presenting features glycogne diagnostic Gnetic are discussed.
Stroage of diagnostic evaluation and nutritional Genetic counseling for glycogen storage disease medical glycogne, including care coordination, genetic counseling, hepatic transplantation, and prenatal disrase, are glycoge.
Conclusions: A guideline that will facilitate the accurate Boost your metabolism naturally and Fueling for strength training management of individuals with glycogen storage disease type III was developed.
This guideline will help health care providers Genetid patients with all forms of glycogen storage disease Genetic counseling for glycogen storage disease III, expedite diagnosis, and minimize stress and negative sequelae glycogrn Genetic counseling for glycogen storage disease diagnosis and inappropriate xounseling.
It will also help identify gaps in scientific knowledge that exist today storzge suggest future studies.
William B. Muscle growth strategies, Terry G. Derks, … John Vissing. Jorge Diogo Da Silva, Ângela Pereira, … Nataliya Tkachenko. Carine A. Halaby, Sarah P. Young, … Priya S. This guideline is intended as an educational resource. Gemetic highlights xounseling practices and therapeutic approaches to the diagnosis and management of the multiple complications conuseling glycogen storage disease GSD disrase III.
InBarbara Illingworth disaese Gerty Coounseling 1 discovered excessive amounts of abnormally Glycogen replenishment formula glycogen in liver and muscle from a patient whom Gilbert Forbes 2 was following up clinically.
Because the stored glycogen had short outer chains, as in a phosphorylase-limit dextrin, it lgycogen suspected glycogej there was counselibg deficiency of the enzyme amylo-1,6-glucosidase AGD ; this prediction Indonesian coffee beans confirmed in Lentils and lentil pasta Most individuals with GSD III survive into gkycogen as in the case of the two patients a male and a female originally reported by Snappes gycogen Genetic counseling for glycogen storage disease Antioxidant-rich smoothies in Both patients improved clinically with wtorage hepatomegaly resolving after puberty, a common finding in affected individuals.
InVan Creveld and Huijing 5 demonstrated diseaze these two Boosts information retention had deficient debranching enzyme activity. Gor was cousneling shown that Genetic counseling for glycogen storage disease debranching enzyme, or AGD, was Genetic counseling for glycogen storage disease in leukocytes of normal individuals, no AGD was found in Geetic leukocytes of individuals with GSD caused Genetic counseling for glycogen storage disease debranching enzyme deficiency.
Antidepressant for elderly human coknseling enzyme gene Kale and sesame recipes a large single-copy gene GenBank M Gfnetic on chromosome 1p21, Calorie intake and health was cloned fpr by Yang Genetic counseling for glycogen storage disease al.
GDE is one of glycoggen few known Genehic with two independent catalytic activities occurring at separate sites on a single polypeptide chain. Hlycogen two activities are Gennetic 1,4-α-d-glucan; 1,4-α-d-glucan 4-α-d-glycosyltransferase and AGD. Couunseling debranching enzyme srorage phosphorylase enzyme are needed for the glycogej degradation of glycogen.
Clinical symptoms attributable to impaired degradation and increased glycogen accumulation include hepatic dysfunction and disease hypoglycemia, pronounced hepatomegaly, and cirrhosisvariable skeletal myopathy, variable cardiomyopathy, and poor growth.
Laboratory findings include increased liver enzyme levels, hypoglycemia, hyperlipidemia, and ketosis. Type III GSD is an autosomal recessive disease that has been reported in many different ethnic groups including Caucasians, Africans, Hispanics, and Asians.
The frequency of the disease is relatively high in Sephardic Jews of North African extraction prevalence Individuals with this disease vary remarkably, both clinically and enzymatically. GSD IIIc affects only the muscle, and GSD IIId affects the muscle and the liver.
During infancy and childhood, the dominant features are hepatomegaly, hypoglycemia, hyperlipidemia, and growth retardation. In individuals with muscle involvement GSD IIIathere is variable myopathy and cardiomyopathy.
Serum CK levels can be useful to identify individuals with muscle involvement; however, normal CK levels do not rule out muscle enzyme deficiency. Hepatomegaly and hepatic symptoms in most individuals with type III GSD improve with age and usually resolve after puberty.
The decrease in liver size can be misleading as progressive liver cirrhosis and hepatic failure can occur, and some individuals develop end-stage liver cirrhosis. Muscle involvement in GSD IIIa is variable; some individuals have asymptomatic cardiomyopathy, some have symptomatic cardiomyopathy leading to death, and others have only skeletal muscle and no apparent heart involvement.
Ventricular hypertrophy is a frequent finding, but overt cardiac dysfunction is rare. Electromyography EMG reveals a widespread myopathy; nerve conduction studies may also be abnormal. There have been reports of successful pregnancies in individuals with GSD III. After a meeting during which published material and personal experience were reviewed by the panel, experts in the various areas reviewed the literature in these areas and drafted the guidelines.
Conflict of interest statements were provided by the participants. All members of the panel reviewed and approved the final guidelines. Consensus was defined as agreement among all members of the panel.
For the most part, the evidence and resulting recommendations are considered expert opinion because additional levels of evidence were not available in the literature.
Penultimate drafts of these guidelines were shared with an external review group consisting of Salvatore DeMauro, MD, William Rhead, MD, Lane Rutledge, MD, Mark Tarnopolsky, MD, PhD, Joseph Wolfsdorf, MB, BCh, and Yuan-Tsong Chen, MD, PhD. Their suggestions were considered by the working group, and changes were made as considered appropriate.
This guideline is directed at a wide range of providers. Type III GSD has variable symptoms depending on the severity and tissues and organs involved. The most common alternative diagnosis in the differential is GSD type Ia. Features common to both disorders are hepatomegaly, hyperlipidemia, and hypoglycemia.
However, some key differences between GSD I and III help differentiate these two disorders. Individuals with GSD I typically present earlier in the first few months of life with severe fasting hypoglycemia 3 to 4 hours after a feed.
In individuals with GSD III, hypoglycemia is usually not as severe as in GSD I because of intact gluconeogenesis and the ability to metabolize peripheral branches of glycogen via phosphorylase. Nonetheless, there are cases of GSD III whose clinical onset is similar to that of GSD I.
Ultrasound imaging of the liver at baseline is similar in GSD I and GSD III, but the presence of nephromegaly in GSD type I can be a clue to the diagnosis.
Blood lactate concentrations rise rapidly in GSD type I as soon as hypoglycemia develops, whereas hyperketonemia with fasting is suggestive of GSD III. Although transaminase elevation and hepatomegaly are common to many primary hepatic diseases and other metabolic disorders, hypoglycemia is uncommon until the development of end-stage liver disease ESLD for most disorders except GSDs.
The extent of the hypoglycemia, transaminase elevation, and hyperlipidemia are usually more severe in GSD III; however, severely affected individuals with GSD VI and GSD IX are being increasingly recognized. GSD type IV does not have hypoglycemia or ketone abnormalities until reaching end stage, and liver dysfunction is usually more pronounced in GSD IV.
Muscle involvement and elevated CK concentrations can occur in GSD IIIa, some hepatic forms of GSD IX, McArdle disease, and late onset GSD II Pompe disease but with clinical and pathophysiologic differences. Muscle weakness in late onset Pompe disease is primarily truncal and proximal, affecting lower more than upper limbs; diaphragm weakness is common and may be the presenting symptom; and hepatomegaly or hypoglycemia are absent.
Respiratory distress caused by involvement of the diaphragm is highly suggestive of Pompe disease and can be a key distinguishing feature not only from GSD III but also from other neuromuscular disorders. Individuals with McArdle disease may have significantly elevated CK levels together with exercise-induced muscle cramps and are prone to develop rhabdomyolysis.
These features help to distinguish it from GSD III. Myopathic motor unit potentials along with the presence of spontaneous activity on EMG may suggest a myositis, but this pattern is often seen with glycogen storage disorders, such as Pompe disease and GSD III.
Rarely, a severe infantile cardiomyopathy can occur in GSD III, 23 which can be difficult to distinguish from Pompe disease and Danon disease. In these primary cardiac disorders, hypoglycemia is not present. There may be hepatomegaly caused by cardiac failure.
A rare variant of phosphorylase kinase deficiency caused by mutations in the PRKAG2 gene can also present with severe infantile hypertrophic cardiomyopathy.
Other metabolic disorders such as Gaucher disease and Niemann-Pick disease may, initially, be confused with GSD because of the presence of hepatomegaly.
In these storage disorders, however, splenomegaly is massive and helps in the differential diagnosis. In GSD III, the administration of glucagon 2 hours after a carbohydrate-rich meal provokes a normal increase in blood glucose BGwhereas, after an overnight fast, glucagon typically provokes no change in BG level.
Critical blood samples drawn at the time of hypoglycemia are useful in evaluation of the various metabolic and endocrine causes Table 2.
The coexistence of hepatomegaly and hypoglycemia should prompt a workup that includes measurement of BG, lactate, uric acid, and hepatic profile including liver function studies, CK, plasma total and free carnitine, acylcarnitine profile, urinalysis, and urine organic acids.
When the diagnosis is unclear, measurement of insulin, growth hormone, cortisol, free fatty acids, beta-hydroxybutyrate, and acetoacetate levels may also be needed.
In addition, the results of newborn screening should be checked because fatty acid oxidation disorders and galactosemia are included both in the differential diagnosis and standard newborn screening panels.
At the time of hypoglycemia, beta-hydroxybutyrate concentration will be elevated, which is in contrast to the hypoketosis characteristic of fatty acid oxidation disorders and hyperinsulinism.
A more detailed workup of the individual who presents with hypoglycemia and hepatomegaly can be found in Scriver's Online Metabolic and Molecular Bases of Inherited Disease. Electromyograms and nerve conduction studies are generally both abnormal showing evidence of myopathy small, short duration motor units and a mixed pattern of myopathy and neuropathy.
Biopsies should lead to a definitive diagnosis in most cases but are critically dependent on the site of the biopsy and correct processing of the tissue. Usually 30—40 mg of tissue or four cores of liver tissue are required for all the studies necessary to make a definitive diagnosis.
In the United States, reliable enzymatic analysis is only available on frozen muscle and liver biopsy samples. Liver histology in those with GSD III can help differentiate it from other liver GSDs. Histopathologic findings of the liver in GSD I include distention of the liver cells by glycogen and fat with uniform glycogen distribution.
Lipid vacuoles are large and frequent.
: Genetic counseling for glycogen storage disease| Description | Fat intake and inflammation novel mutations included one frameshift diseasr in Counselong c. Standardized gross Genetic counseling for glycogen storage disease fine motor testing in children is recommended to assess function Genetic counseling for glycogen storage disease to age-level fr, to identify specific coumseling areas of impairment and decreased function, and to optimize participation. Download PDF. Successful pregnancy in a woman with glycogen storage disease type III. Defects in a number of genes that encode proteins involved in glucose or fructose metabolism can result in a clinical picture similar to that of some of the GSDs, and are therefore included in this sequencing panel. Google Scholar Van Creveld S, Huijing F. |
| Glycogen storage disease type IX | Eur J Pediatr ; suppl 2 : S43—S PubMed PubMed Central Google Scholar. Cornelio F, Bresolin N, Singer PA, DiMauro S, Rowland LP. Clinical varieties of neuromuscular disease in debrancher deficiency. Arch Neurol ; 41 : — Hobson-Webb LD, Austin SL, Bali D, Kishnani PS. The electrodiagnostic characteristics of Glycogen Storage Disease Type III. Genet Med ; 12 : — Kotb MA, Abdallah HK, Kotb A. Liver glycogenoses: are they a possible cause of polyneuropathy? A cross-sectional study. J Trop Pediatr ; 50 : — PubMed Google Scholar. Labrune P, Huguet P, Odievre M. Cardiomyopathy in glycogen-storage disease type III: clinical and echographic study of 18 patients. Pediatr Cardiol ; 12 : — Miller CG, Alleyne GA, Brooks SE. Gross cardiac involvement in glycogen storage disease type 3. Br Heart J ; 34 : — CAS PubMed PubMed Central Google Scholar. Moses SW, Wanderman KL, Myroz A, Frydman M. Cardiac involvement in glycogen storage disease type III. Eur J Pediatrics ; : — CAS Google Scholar. Lee PJ, Deanfield JE, Burch M, Baig K, McKenna WJ, Leonard JV. Comparison of the functional significance of left ventricular hypertrophy in hypertrophic cardiomyopathy and glycogenosis type III. Am J Cardiol ; 79 : — Shen J, Bao Y, Chen YT. Hum Mutat ; 9 : 37— Article CAS PubMed Google Scholar. Vertilus SM, Austin SL, Foster KS, et al. Echocardiographic manifestations of Glycogen Storage Disease III: increase in wall thickness and left ventricular mass over time. Cabrera-Abreu J, Crabtree NJ, Elias E, Fraser W, Cramb R, Alger S. Bone mineral density and markers of bone turnover in patients with glycogen storage disease types I, III and IX. J Inherit Metab Dis ; 27 : 1—9. Lee PJ, Patel A, Hindmarsh PC, Mowat AP, Leonard JV. The prevalence of polycystic ovaries in the hepatic glycogen storage diseases: its association with hyperinsulinism. Clin Endocrinol Oxf ; 42 : — Confino E, Pauzner D, Lidor A, Yedwab G, David M. Pregnancy associated with amylo-1,6-glucosidase deficiency Forbe's disease. Case report. Br J Obstet Gynaecol ; 91 : — Bhatti S, Parry E. Successful pregnancy in a woman with glycogen storage disease type III. Aust N Z J Obstet Gynaecol ; 46 : — Mendoza A, Fisher NC, Duckett J, et al. Successful pregnancy in a patient with type III glycogen storage disease managed with cornstarch supplements. Br J Obstet Gynaecol ; : — Elpeleg ON. The molecular background of glycogen metabolism disorders. J Pediatr Endocrinol Metab ; 12 : — 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 ; : — Clayton PT. Diagnosis of inherited disorders of liver metabolism. J Inherit Metab Dis ; 26 : — Wolfsdorf JI, Holm IA, Weinstein DA. Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. Endocrinol Metab Clin North Am ; 28 : — Lee P, Mather S, Owens C, Leonard J, Dicks-Mireaux C. Hepatic ultrasound findings in the glycogen storage diseases. Br J Radiol ; 67 : — Binkiewicz A, Senior B. Decreased ketogenesis in von Gierke's disease type I glycogenosis. J Pediatr ; 83 : — Fernandes J, Pikaar NA. Ketosis in hepatic glycogenosis. Arch Dis Child ; 47 : 41— Fischer KF, Lees JA, Newman JH. Hypoglycemia in hospitalized patients. Causes and outcomes. N Engl J Med ; : — Wolf AD, Lavine JE. Hepatomegaly in neonates and children. Pediatr Rev ; 21 : — Moses SW, Parvari R. The variable presentations of glycogen storage disease type IV: a review of clinical, enzymatic and molecular studies. Curr Mol Med ; 2 : — Mellies U, Lofaso F. Pompe disease: a neuromuscular disease with respiratory muscle involvement. Respir Med ; : — Servidei S, Metlay LA, Chodosh J, DiMauro S. Fatal infantile cardiopathy caused by phosphorylase b kinase deficiency. J Pediatr ; 1 Pt 1 : 82— New York, NY, McGraw-Hill, Ugawa Y, Inoue K, Takemura T, Iwamasa T. Accumulation of glycogen in sural nerve axons in adult-onset type III glycogenosis. Ann Neurol ; 19 : — Kiechl S, Kohlendorfer U, Thaler C, et al. Different clinical aspects of debrancher deficiency myopathy. J Neurol Neurosurg Psychiatry ; 67 : — Mineo I, Kono N, Hara N, et al. Myogenic hyperuricemia. A common pathophysiologic feature of glycogenosis types III, V, and VII. N Engl J Med ; : 75— Chen YT, Kishnani PS, Koeberl DD, Glycogen storage diseases. McAdams AJ, Hug G, Bove KE. Glycogen storage disease, types I to X: criteria for morphologic diagnosis. Hum Pathol ; 5 : — DiMauro S, Hartwig GB, Hays A, et al. Debrancher deficiency: neuromuscular disorder in 5 adults. Ann Neurol ; 5 : — Miranda AF, DiMauro S, Antler A, Stern LZ, Rowland LP. Glycogen debrancher deficiency is reproduced in muscle culture. Ann Neurol ; 9 : — Shen JJ, Chen YT. Molecular characterization of glycogen storage disease type III. Maire I, Baussan C, Moatti N, Mathieu M, Lemonnier A. Biochemical diagnosis of hepatic glycogen storage diseases: 20 years French experience. Clin Biochem ; 24 : — Shaiu WL, Kishnani PS, Shen J, Liu HM, Chen YT. Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease. Mol Genet Metab ; 69 : 16— DiMauro S, Tsujino S, Nonlysosomal glycogenoses. In: Engel AG, Franzini-Armstrong C eds Myology. New York, NY, McGraw Hill, ; — Maire I, Mathieu M. Possible prenatal diagnosis of type III glycogenosis. J Inherit Metab Dis ; 9 : 89— Shin YS. Diagnosis of glycogen storage disease. J Inherit Metab Dis ; 13 : — Besley GT, Cohen PT, Faed MJ, Wolstenholme J. Amylo-1,6-glucosidase activity in cultured cells: a deficiency in type III glycogenosis with prenatal studies. Prenat Diagn ; 3 : 13— Shin YS, Ungar R, Rieth M, Endres W. A simple assay for amylo-1,6-glucosidase to detect heterozygotes for glycogenosis type III in erythrocytes. Clin Chem ; 30 : — Shin YS, Rieth M, Tausenfreund J, Endres W. First trimester diagnosis of glycogen storage disease type II and type III. J Inherit Metab Dis ; 12 suppl 2 : — Yang BZ, Ding JH, Brown BI, Chen YT. Definitive prenatal diagnosis for type III glycogen storage disease. Am J Hum Genet ; 47 : — Goldstein JL, Austin SL, Boyette K, et al. Molecular analysis of the AGL gene: identification of 25 novel mutations and evidence of genetic heterogeneity in patients with Glycogen Storage Disease Type III. Shen J, Bao Y, Liu HM, Lee P, Leonard JV, Chen YT. Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle. J Clin Invest ; 98 : — Okubo M, Horinishi A, Nakamura N, et al. Hum Genet ; : 1—5. Cheng A, Zhang M, Okubo M, Omichi K, Saltiel AR. Distinct mutations in the glycogen debranching enzyme found in glycogen storage disease type III lead to impairment in diverse cellular functions. Hum Mol Genet ; 18 : — Lucchiari S, Santoro D, Pagliarani S, Comi GP. Clinical, biochemical and genetic features of glycogen debranching enzyme deficiency. Acta Myol ; 26 : 72— Pearson CM. Glycogen metabolism and storage diseases of types III, IV and V. Am J Clin Pathol ; 50 : 29— Olson LJ, Reeder GS, Noller KL, Edwards WD, Howell RR, Michels VV. Cardiac involvement in glycogen storage disease III: morphologic and biochemical characterization with endomyocardial biopsy. Am J Cardiol ; 53 : — Coleman RA, Winter HS, Wolf B, Gilchrist JM, Chen YT. Glycogen storage disease type III glycogen debranching enzyme deficiency : correlation of biochemical defects with myopathy and cardiomyopathy. Ann Intern Med ; : — Carvalho JS, Matthews EE, Leonard JV, Deanfield J. Cardiomyopathy of glycogen storage disease type III. Heart Vessels ; 8 : — Talente GM, Coleman RA, Alter C, et al. Glycogen storage disease in adults. Akazawa H, Kuroda T, Kim S, Mito H, Kojo T, Shimada K. Specific heart muscle disease associated with glycogen storage disease type III: clinical similarity to the dilated phase of hypertrophic cardiomyopathy. Eur Heart J ; 18 : — Rossignol AM, Meyer M, Rossignol B, Palcoux MP, Raynaud EJ, Bost M. Arch Fr Pediatr ; 36 : — Cochrane AB, Fedson SE, Cronin DC II, Nesiritide as bridge to multi-organ transplantation: a case report. Transplant Proc ; 39 : — Levine JC, Kishnani PS, Chen YT, Herlong JR, Li JS. Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease. Pediatr Cardiol ; 29 : — Ogimoto A, Okubo M, Okayama H, et al. A Japanese patient with cardiomyopathy caused by a novel mutation RX in the AGL gene. Circ J ; 71 : — Smit GP, Fernandes J, Leonard JV, et al. The long-term outcome of patients with glycogen storage diseases. Keddad KRS, Baussan C, Chalas J, et al. Blood lipids and rheological modifications in glycogen storage disease. Clin Biochem ; 29 : 73— Hershkovitz E, Donald A, Mullen M, Lee PJ, Leonard JV. Blood lipids and endothelial function in glycogen storage disease type III. J Inherit Metab Dis ; 22 : — Fernandes J, Leonard JV, Moses SW, et al. Glycogen storage disease: recommendations for treatment. Eur J Pediatr ; : — Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc ; 93 : — Slonim AE, Coleman RA, Moses WS. Myopathy and growth failure in debrancher enzyme deficiency: improvement with high-protein nocturnal enteral therapy. J Pediatr ; : — Slonim AE, Weisberg C, Benke P, Evans OB, Burr IM. Reversal of debrancher deficiency myopathy by the use of high-protein nutrition. Ann Neurol ; 11 : — Borowitz SM, Greene HL. Cornstarch therapy in a patient with type III glycogen storage disease. J Pediatr Gastroenterol Nutr ; 6 : — Mundy HR, Williams JE, Lee PJ, Fewtrell MS. Reduction in bone mineral density in glycogenosis type III may be due to a mixed muscle and bone deficit. J Inherit Metab Dis ; 31 : — Lee PJ, Ferguson C, Alexander FW. Symptomatic hyperinsulinism reversed by dietary manipulation in glycogenosis type III. J Inherit Metab Dis ; 20 : — Dagli AI, Zori RT, McCune H, Ivsic T, Maisenbacher MK, Weinstein DA Reversal of glycogen storage disease type IIIa-related cardiomyopathy with modification of diet [published online ahead of print March 30, ]. J Inherit Metab Dis doi: Portmann B, Thompson RJ, Roberts EA, Paterson AC. Genetic and metabolic liver disease , 5 ed. London, Churchill Livingstone, Cosme A, Montalvo I, Sanchez J, et al. Gastroenterol Hepatol ; 28 : — Shimizu J, Shiraishi H, Sakurabayashi S, et al. Nippon Shokakibyo Gakkai Zasshi ; 79 : — Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease MELD and allocation of donor livers. Gastroenterology ; : 91— Merion RM, Schaubel DE, Dykstra DM, Freeman RB, Port FK, Wolfe RA. The survival benefit of liver transplantation. Am J Transplant ; 5 : — Davis MK, Weinstein DA. Pediatr Transplant ; 12 : — Iyer SG, Chen CL, Wang CC, et al. Long-term results of living donor liver transplantation for glycogen storage disorders in children. Liver Transpl ; 13 : — Moses SW, Gadoth N, Bashan N, Ben-David E, Slonim A, Wanderman KL. Neuromuscular involvement in glycogen storage disease type III. Acta Paediatr Scand ; 75 : — Tolun AA, Boyd KF, Austin SL, et al. Utility of a urinary tetrasaccharide as a biomarker for glycogen storage disease type III. San Diego, California, Marbini A, Gemignani F, Saccardi F, Rimoldi M. Debrancher deficiency neuromuscular disorder with pseudohypertrophy in two brothers. J Neurol ; : — Parvari R, Moses S, Shen J, Hershkovitz E, Lerner A, Chen YT. Eur J Hum Genet ; 5 : — Kiechl S, Willeit J, Vogel W, Kohlendorfer U, Poewe W. Reversible severe myopathy of respiratory muscles due to adult-onset type III glycogenosis. Neuromuscul Disord ; 9 : — Haller RG, Vissing J, Functional evaluation of metabolic myopathy. Haller RG, Wyrick P, Taivassalo T, Vissing J. Aerobic conditioning: an effective therapy in McArdle's disease. Ann Neurol ; 59 : — Chan JC, Cockram CS, Critchley JA. Drug-induced disorders of glucose metabolism. Mechanisms and management. Drug Saf ; 15 : — Oki Y, Okubo M, Tanaka S, Nakanishi K, Kobayashi T, Murase T. Diabetes mellitus secondary to glycogen storage disease type III. Diabet Med ; 17 : — Giannitrapani L, Soresi M, La Spada E, Cervello M, D'Alessandro N, Montalto G. Sex hormones and risk of liver tumor. Ann N Y Acad Sci ; : — Mairovitz V, Labrune P, Fernandez H, Audibert F, Frydman R. Contraception and pregnancy in women affected by glycogen storage diseases. Eur J Pediatr ; suppl 1 : S97—S Bahamondes L, Monteiro-Dantas C, Espejo-Arce X, et al. A prospective study of the forearm bone density of users of etonorgestrel- and levonorgestrel-releasing contraceptive implants. Hum Reprod ; 21 : — Lee P. Ngai SH. Effects of anesthetics on various organs. Mohart D, Russo P, Tobias JD. Perioperative management of a child with glycogen storage disease type III undergoing cardiopulmonary bypass and repair of an atrial septal defect. Paediatr Anaesth ; 12 : — Roe CR, Mochel F. Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential. J Inherit Metab Dis ; 29 : — Gregory BL, Shelton GD, Bali DS, Chen YT, Fyfe JC. Glycogen storage disease type IIIa in curly-coated retrievers. J Vet Intern Med ; 21 : 40— Download references. This project was supported by educational grants from the Association for Glycogen Storage Disease, US, and the American College of Medical Genetics Foundation. We thank Salvatore DeMauro, MD, Mark Tarnopolsky, MD, PhD, William Rhead, MD, Lane Rutledge, MD, Joseph Wolfsdorf, MD, and Yuan-Tsong Chen, MD, PhD, for their prepublication reviews of this guideline. Departments of Pediatrics, Duke University Medical Center, Durham, North Carolina. Community and Family Medicine, Duke University Medical Center, Durham, North Carolina. Medicine, Duke University Medical Center, Durham, North Carolina. Department of Pediatrics, Nemours Children's Clinic, Jacksonville, Florida. Department of Pediatrics, Columbia University Medical Center, New York, New York. Departments of Surgery and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas. Departments of Neurology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida. American College of Medical Genetics, Bethesda, Maryland. You can also search for this author in PubMed Google Scholar. Correspondence to Priya S Kishnani. Disclaimer: ACMG standards and guidelines are designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services. Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticists should apply their own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these standards and guidelines. Reprints and permissions. Kishnani, P. et al. Glycogen Storage Disease Type III diagnosis and management guidelines. Genet Med 12 , — Download citation. Issue Date : July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content Thank you for visiting nature. nature genetics in medicine acmg practice guideline article. Download PDF. Abstract Purpose: Glycogen storage disease type III is a rare disease of variable clinical severity affecting primarily the liver, heart, and skeletal muscle. Glycogen storage diseases Article 07 September Diagnostic accuracy and the first genotype—phenotype correlation in glycogen storage disease type V Article 05 December Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring Article 02 July PURPOSE This guideline is intended as an educational resource. Overview and general background GDE is one of the few known proteins with two independent catalytic activities occurring at separate sites on a single polypeptide chain. Target audience This guideline is directed at a wide range of providers. Table 1 Differential diagnosis of GSD III Full size table. Table 2 Suggested laboratory evaluations for a patient with hypoglycemia and hepatomegaly Full size table. Biochemical analysis of GDE activity and glycogen content Clinical assays measure overall GDE activity in the affected tissue samples. Table 3 Biochemical and histologic characteristics of selected GSD types Full size table. Ventricular hypertrophy and cardiomyopathy Individuals with GSD III do not develop valvular disease such as semilunar or atrioventricular valve regurgitation, but left ventricular hypertrophy LVH seems to be common in GSD III, although only a small fraction of individuals with GSD III actually develop cardiomyopathy symptomatic ventricular hypertrophy. Routine evaluation and management Based on currently available data regarding cardiovascular involvement in GSD III, several recommendations for evaluation and management can be made. Infants and young children with GSD IIIa and IIIb The initial focus of the diet for the infant and young child with either GSD IIIa or IIIb is to prevent hypoglycemia. Adults with GSD IIIa and IIIb The emphasis of the diet for the adult with GSD IIIa is on a higher percentage of protein. Liver transplantation and organ allocation Although individuals with GSD III may develop histologic evidence of cirrhosis, so long as their synthetic function remains normal or well preserved, liver transplantation LT is not necessary. Implications for muscle energy metabolism and exercise Muscle glycogen is a crucial fuel for anaerobic metabolism to support maximal effort and is broken down by myophosphorylase and muscle debranching enzyme. Physical therapy Musculoskeletal assessment is recommended with respect to potential alterations in alignment described earlier hypermobility, increased width of base of support, anterior pelvic tilt, genu valgum and recurvatum, hindfoot valgus, and forefoot varus. GENERAL MEDICAL CARE General medical care should be individualized as disease manifestations vary. No caption available. Full size image. Similar content being viewed by others. References Illingworth B, Cori GT. CAS PubMed Google Scholar Forbes GB. CAS PubMed Google Scholar Illingworth B, Cori GT, Cori CF. CAS PubMed Google Scholar Snappes I, Van Creveld S. Google Scholar Van Creveld S, Huijing F. CAS PubMed Google Scholar Huijing F. CAS PubMed Google Scholar Yang BZ, Ding JH, Enghild JJ, Bao Y, Chen YT. CAS PubMed Google Scholar Bao Y, Dawson TL Jr, Chen YT. CAS PubMed Google Scholar Bao Y, Yang BZ, Dawson TL Jr, Chen YT. CAS PubMed Google Scholar Howell R, Williams J, The glycogen storage diseases. Google Scholar Van Hoof F, Hers HG. CAS PubMed Google Scholar Angelini C, Martinuzzi A, Vergani L, Glycogen storage diseases of muscle. Google Scholar Ding JH, de Barsy T, Brown BI, Coleman RA, Chen YT. CAS PubMed Google Scholar Sugie H, Fukuda T, Ito M, Sugie Y, Kojoh T, Nonaka I. CAS PubMed Google Scholar Lee P, Burch M, Leonard JV. CAS PubMed Google Scholar Coleman RA, Winter HS, Wolf B, Chen YT. CAS PubMed Google Scholar Labrune P, Trioche P, Duvaltier I, Chevalier P, Odievre M. CAS PubMed Google Scholar Demo E, Frush D, Gottfried M, Koepke J, Boney A, Bali D, et al. CAS PubMed Google Scholar Siciliano M, De Candia E, Ballarin S, et al. CAS PubMed Google Scholar Matern D, Starzl TE, Arnaout W, et al. PubMed PubMed Central Google Scholar Cornelio F, Bresolin N, Singer PA, DiMauro S, Rowland LP. CAS PubMed Google Scholar Hobson-Webb LD, Austin SL, Bali D, Kishnani PS. CAS PubMed Google Scholar Kotb MA, Abdallah HK, Kotb A. PubMed Google Scholar Labrune P, Huguet P, Odievre M. CAS PubMed Google Scholar Miller CG, Alleyne GA, Brooks SE. CAS PubMed PubMed Central Google Scholar Moses SW, Wanderman KL, Myroz A, Frydman M. CAS Google Scholar Lee PJ, Deanfield JE, Burch M, Baig K, McKenna WJ, Leonard JV. CAS PubMed Google Scholar Shen J, Bao Y, Chen YT. Article CAS PubMed Google Scholar Vertilus SM, Austin SL, Foster KS, et al. PubMed PubMed Central Google Scholar Cabrera-Abreu J, Crabtree NJ, Elias E, Fraser W, Cramb R, Alger S. CAS PubMed Google Scholar Lee PJ, Patel A, Hindmarsh PC, Mowat AP, Leonard JV. CAS Google Scholar Confino E, Pauzner D, Lidor A, Yedwab G, David M. CAS PubMed Google Scholar Bhatti S, Parry E. PubMed Google Scholar Mendoza A, Fisher NC, Duckett J, et al. CAS PubMed Google Scholar Elpeleg ON. CAS PubMed Google Scholar Lucchiari S, Fogh I, Prelle A, et al. CAS PubMed Google Scholar Clayton PT. CAS PubMed Google Scholar Wolfsdorf JI, Holm IA, Weinstein DA. CAS PubMed Google Scholar Lee P, Mather S, Owens C, Leonard J, Dicks-Mireaux C. CAS PubMed Google Scholar Binkiewicz A, Senior B. CAS PubMed Google Scholar Fernandes J, Pikaar NA. CAS PubMed PubMed Central Google Scholar Fischer KF, Lees JA, Newman JH. CAS PubMed Google Scholar Wolf AD, Lavine JE. CAS PubMed Google Scholar Moses SW, Parvari R. CAS PubMed Google Scholar Mellies U, Lofaso F. PubMed Google Scholar Servidei S, Metlay LA, Chodosh J, DiMauro S. New York, NY, McGraw-Hill, Google Scholar Ugawa Y, Inoue K, Takemura T, Iwamasa T. CAS PubMed Google Scholar Kiechl S, Kohlendorfer U, Thaler C, et al. CAS PubMed PubMed Central Google Scholar Mineo I, Kono N, Hara N, et al. CAS PubMed Google Scholar Chen YT, Kishnani PS, Koeberl DD, Glycogen storage diseases. New York, NY, McGraw-Hill, Google Scholar McAdams AJ, Hug G, Bove KE. CAS PubMed Google Scholar DiMauro S, Hartwig GB, Hays A, et al. CAS PubMed Google Scholar Miranda AF, DiMauro S, Antler A, Stern LZ, Rowland LP. CAS PubMed Google Scholar Shen JJ, Chen YT. CAS PubMed Google Scholar Maire I, Baussan C, Moatti N, Mathieu M, Lemonnier A. CAS PubMed Google Scholar Shaiu WL, Kishnani PS, Shen J, Liu HM, Chen YT. CAS PubMed Google Scholar DiMauro S, Tsujino S, Nonlysosomal glycogenoses. Google Scholar Maire I, Mathieu M. CAS PubMed Google Scholar Shin YS. CAS PubMed Google Scholar Besley GT, Cohen PT, Faed MJ, Wolstenholme J. CAS PubMed Google Scholar Shin YS, Ungar R, Rieth M, Endres W. CAS PubMed Google Scholar Shin YS, Rieth M, Tausenfreund J, Endres W. PubMed Google Scholar Yang BZ, Ding JH, Brown BI, Chen YT. CAS PubMed PubMed Central Google Scholar Goldstein JL, Austin SL, Boyette K, et al. CAS PubMed Google Scholar Shen J, Bao Y, Liu HM, Lee P, Leonard JV, Chen YT. CAS PubMed PubMed Central Google Scholar Okubo M, Horinishi A, Nakamura N, et al. CAS PubMed Google Scholar Cheng A, Zhang M, Okubo M, Omichi K, Saltiel AR. CAS PubMed PubMed Central Google Scholar Lucchiari S, Santoro D, Pagliarani S, Comi GP. CAS PubMed PubMed Central Google Scholar Pearson CM. CAS PubMed Google Scholar Olson LJ, Reeder GS, Noller KL, Edwards WD, Howell RR, Michels VV. CAS PubMed Google Scholar Coleman RA, Winter HS, Wolf B, Gilchrist JM, Chen YT. CAS PubMed Google Scholar Carvalho JS, Matthews EE, Leonard JV, Deanfield J. CAS PubMed Google Scholar Talente GM, Coleman RA, Alter C, et al. CAS PubMed Google Scholar Akazawa H, Kuroda T, Kim S, Mito H, Kojo T, Shimada K. CAS PubMed Google Scholar Rossignol AM, Meyer M, Rossignol B, Palcoux MP, Raynaud EJ, Bost M. CAS PubMed Google Scholar Cochrane AB, Fedson SE, Cronin DC II, Nesiritide as bridge to multi-organ transplantation: a case report. CAS PubMed Google Scholar Levine JC, Kishnani PS, Chen YT, Herlong JR, Li JS. Google Scholar Ogimoto A, Okubo M, Okayama H, et al. CAS PubMed Google Scholar Smit GP, Fernandes J, Leonard JV, et al. CAS PubMed Google Scholar Keddad KRS, Baussan C, Chalas J, et al. CAS PubMed Google Scholar Hershkovitz E, Donald A, Mullen M, Lee PJ, Leonard JV. CAS PubMed Google Scholar Fernandes J, Leonard JV, Moses SW, et al. CAS PubMed Google Scholar Goldberg T, Slonim AE. CAS PubMed Google Scholar Slonim AE, Coleman RA, Moses WS. CAS PubMed Google Scholar Slonim AE, Weisberg C, Benke P, Evans OB, Burr IM. CAS PubMed Google Scholar Borowitz SM, Greene HL. CAS PubMed Google Scholar Mundy HR, Williams JE, Lee PJ, Fewtrell MS. CAS PubMed Google Scholar Lee PJ, Ferguson C, Alexander FW. CAS PubMed Google Scholar Dagli AI, Zori RT, McCune H, Ivsic T, Maisenbacher MK, Weinstein DA Reversal of glycogen storage disease type IIIa-related cardiomyopathy with modification of diet [published online ahead of print March 30, ]. Google Scholar Portmann B, Thompson RJ, Roberts EA, Paterson AC. London, Churchill Livingstone, Google Scholar Cosme A, Montalvo I, Sanchez J, et al. CAS PubMed Google Scholar Shimizu J, Shiraishi H, Sakurabayashi S, et al. CAS PubMed Google Scholar Wiesner R, Edwards E, Freeman R, et al. PubMed Google Scholar Merion RM, Schaubel DE, Dykstra DM, Freeman RB, Port FK, Wolfe RA. PubMed Google Scholar Davis MK, Weinstein DA. PubMed Google Scholar Iyer SG, Chen CL, Wang CC, et al. PubMed Google Scholar Moses SW, Gadoth N, Bashan N, Ben-David E, Slonim A, Wanderman KL. CAS PubMed Google Scholar Tolun AA, Boyd KF, Austin SL, et al. San Diego, California, Google Scholar Marbini A, Gemignani F, Saccardi F, Rimoldi M. CAS PubMed Google Scholar Parvari R, Moses S, Shen J, Hershkovitz E, Lerner A, Chen YT. CAS PubMed Google Scholar Kiechl S, Willeit J, Vogel W, Kohlendorfer U, Poewe W. CAS PubMed Google Scholar Haller RG, Vissing J, Functional evaluation of metabolic myopathy. Google Scholar Haller RG, Wyrick P, Taivassalo T, Vissing J. PubMed Google Scholar Chan JC, Cockram CS, Critchley JA. CAS PubMed Google Scholar Oki Y, Okubo M, Tanaka S, Nakanishi K, Kobayashi T, Murase T. CAS PubMed Google Scholar Giannitrapani L, Soresi M, La Spada E, Cervello M, D'Alessandro N, Montalto G. CAS PubMed Google Scholar Mairovitz V, Labrune P, Fernandez H, Audibert F, Frydman R. CAS PubMed Google Scholar Bahamondes L, Monteiro-Dantas C, Espejo-Arce X, et al. CAS PubMed Google Scholar Lee P. CAS PubMed Google Scholar Ngai SH. CAS PubMed Google Scholar Mohart D, Russo P, Tobias JD. PubMed Google Scholar Roe CR, Mochel F. CAS PubMed Google Scholar Gregory BL, Shelton GD, Bali DS, Chen YT, Fyfe JC. PubMed Google Scholar Download references. Acknowledgements This project was supported by educational grants from the Association for Glycogen Storage Disease, US, and the American College of Medical Genetics Foundation. View author publications. Additional information Disclosure: The authors declare no conflict of interest. Rights and permissions Reprints and permissions. About this article Cite this article Kishnani, P. Copy to clipboard. This article is cited by Dietary Management of Metabolic Liver Disease Tanyaporn K. Kaenkumchorn Shreena Patel Rohit Kohli Current Hepatology Reports The biallelic novel pathogenic variants in AGL gene in a chinese patient with glycogen storage disease type III Jing Wang Yuping Yu Jianbo Shu BMC Pediatrics Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa: an observational study Philip J. Bonnardeaux A, Bichet DG. Inherited disorders of the renal tubule. In: Yu ASL, Chertow GM, Luyckx VA, Marsden PA, Taal MW, Skorecki K, eds. Brenner and Rector's The Kidney. Philadelphia, PA: Elsevier; chap Kishnani PS, Chen Y-T. Defects in metabolism of carbohydrates. In: Kliegman RM, St. Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM, eds. Nelson Textbook of Pediatrics. Litwack G. Glycogen and glycogenolysis. In: Litwack G, ed. Human Biochemistry. Philadelphia, PA: Elsevier; chap 7. Santos BL, Souza CF, Schuler-Faccini L, et al. Glycogen storage disease type 1: clinical and laboratory profile. J Pediatr Rio J. PMID: pubmed. Reviewed by: Anna C. Edens Hurst, MD, MS, Associate Professor in Medical Genetics, The University of Alabama at Birmingham, Birmingham, AL. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A. Editorial team. Share Facebook Twitter Linkedin Email Home Health Library. Von Gierke disease Type I glycogen storage disease; von Gierke's disease. Causes Von Gierke disease occurs when the body lacks the protein enzyme that releases glucose from glycogen. Symptoms These are symptoms of von Gierke disease: Constant hunger and need to eat often Easy bruising and nosebleeds Fatigue Irritability Puffy cheeks, thin chest and limbs, and swollen belly. Exams and Tests Your health care provider will perform a physical exam. The exam may show signs of: Delayed puberty Enlarged liver Gout Inflammatory bowel disease Liver tumors Severe low blood sugar Stunted growth or failure to grow Children with this condition are usually diagnosed before age 1 year. Tests that may be done include: Biopsy of liver or kidney Blood sugar test Genetic testing Lactic acid blood test Triglyceride level Uric acid blood test If a person has this disease, test results will show low blood sugar and high levels of lactate produced from lactic acid , blood fats lipids , and uric acid. Treatment The goal of treatment is to avoid low blood sugar. |
| Von Gierke disease | In addition, the liver biopsy showed cirrhosis and suggested GSD-IV. He had also successfully received a partial liver transplant at the age of 2. Moreover, the targeted NGS panel revealed two variants in GBE1 gene. A homozygous deleterious variant, namely c. GluVal 15 , and another novel homozygous variant c. Val98Leu , were additionally detected in the GBE1 gene. The new variant was not listed in Iranome and gnomAD databases or described in the related literature, so it could be interpreted as a variant of uncertain significance VUS. Her liver biopsy also suggested unclassified GSD with marked fibrosis. Using TGS, a novel homozygous missense variant, c. GluGly , was detected in PYGL gene, indicating GSD-VI Table 2. Para-clinical results also showed increased TG, TChol, BCR, AST, and ALT Table 1. Histopathological studies of his liver biopsy also suggested GSD-I or III with mild fibrosis. However, a homozygous pathogenic deletion variant, c. Asp77del , was detected in the liver isoform glycogen phosphorylase, the PYGL gene Table 2 Her liver biopsy also showed unclassified GSD with fibrosis. A homozygous pathogenic variant, c. Arg44Ter , was additionally detected in a PHKG2 gene by TGS. This missense mutation had been previously reported in patients with GSD-IXc 17 , 18 , The results of liver histopathological studies also showed unclassified GSD with bridging fibrosis. Using TGS analysis additionally revealed a novel heterozygous variant, c. Leu45His , in the glycogen phosphorylase kinase regulatory sub-unit beta gene, PHKB GSD-IXb. No other pathogenic variants were detected in other GSD genes in the panel. She was referred because of poor feeding at the age of 3. Laboratory investigations also showed elevated TG, TChol, LDH, Alb, AST, and ALT, as well as leukopenia and acidosis Table 1. The liver biopsy revealed unclassified GSD, and moderate periportal fibrosis. She harbored three novel variants, namely one heterozygote variant c. LeuPhe in the SLC37A4 gene and two homozygote variants c. and c. GlnArg in the PHKB gene. The pathogenic novel variant, c. As a result, she was most probably suffering from IXb, whose symptoms tended to appear with increasing age. Histopathological studies of his liver biopsy also suggested unclassified GSD, with cirrhosis. Using TGS, a novel heterozygous variant, c. Arg5His , was detected in phosphoglycerate mutase gene, the PGAM2 GSD-X. To note, GSD-X is an autosomal recessive disorder and the detection of a single heterozygous variant did not confirm the diagnosis. Nevertheless, lack of a second pathogenic allele or any identified pseudo-deficiency variant had left the molecular diagnosis of this patient in question. Pulmonary hypertension, moderate mitral regurgitation, and mild tricuspid regurgitation were also observed. Moreover, the liver biopsy results revealed cirrhosis, which was suggestive of unclassified GSD. A novel heterozygous variant, c. MetLeu , was further detected in the PRKAG2 gene by TGS and implied PRKAG2 deficiency i. GSD of heart—lethal congenital. Since the PRKAG2 deficiency is an autosomal dominant inheritance with full penetrance, single heterozygote variants could confirm all of her clinical, molecular, and biochemical results. The diagnosis of none of the GSD and non-GSD-associated genes was confirmed in patient no. She was a 2-year-old girl, who presented with hepatomegaly, clubbed fingers, failure to thrive, diarrhea, vomiting, as well as high platelet count, AST, ALT and low uric acid Table 1. Her liver biopsy was suggestive of GSD or lipid storage disease with mild fibrosis. No deleterious mutations were also detected in any of the related GSD genes analyzed. There was, therefore, no definite diagnosis for this patient. In five patients, the features of liver histopathology were suggestive of unclassified GSD, molecular genetic investigations of these patients which confirmed the diagnosis of GSD-VI in one patient no. In one case, not only the features of liver histopathology were shown ambiguous results, but also no deleterious mutations were detected in any of the GSD genes analyzed no. Classification and sub-typing of GSD patients are important steps towards personalized patient management, which can help clinicians practice the best and the most correct therapy with the fewest adverse events for patients Here, the first and largest cohort is reported about GSD sub-typing from the Middle East and Asia. It is also the first study, addressing clinical characteristics and genomics in sub-typing of patients with GSDs from Iranian population. In this cohort of 14 pediatric patients, 10 novel pathogenic variants in the SLC37A , AGL , GBE1 , PHKB , PGAM2 and PRKAG2 genes were found. Notably, GSD-IX was detected in three patients, which had not been reported from Iran, so far. It means that it has been overlooked in our population because of subtle patient presentations and self-limited outcomes as well as lack of molecular diagnosis analyses. Therefore, it has been classified as other types of GSD, such as GSD-III or VI. Chronic liver diseases, such as cirrhosis and fibrosis, have been also rarely reported in some types of GSDs e. GSD-VI and IX In addition, asymptomatic heart problems with liver involvement were identified in a GSD of the heart-lethal congenital disorder i. PRKAG2 deficiency in one patient in our study cohort. To the best of our knowledge, we report for the first time liver cirrhosis in GSD-X and GSD of the heart-lethal congenital i. PRKAG2 deficiency. In this pathological report, 13 patients were suggestive to have one type of GSD without exact sub-typing, so molecular genetic analysis namely, targeted genome sequencing based on NGS was performed, confirming the exact type of GSD. According to these results, molecular genetic testing, especially NGS-based GSD or inborn inherited metabolic panel exome sequencing, was recommended for definite diagnosis of GSD sub-types prior to invasive liver biopsy. Liver histopathology may also be a powerful and effective method for monitoring long-term liver complications and evaluating the status of the liver in these patients, but not for confirming diagnosis and accurate sub-typing. NGS-based targeted exome sequencing is thus reported as the best future routine method of molecular diagnosis. This is especially useful for complex disorders with less specific clinical findings Nevertheless, in defining the syndromes or diseases like GSD, clinical features or biochemical phenotypes can effectively address a particular pathway or a group of genes responsible for the disease. In such cases, a custom-targeted gene-sequencing panel has been confirmed to be an efficient as well as time- and cost-effective technique with high diagnostic yields Analytical workflows for the diagnosis of GSD diseases are not fully standardized; however, a useful and practical approach based on clinical and biochemical evaluations followed by targeted molecular analysis was reported later, as shown in Fig. Moreover, using custom-target sequencing vs. exome sequencing would become a routine technique due to the focus on a limited number of suspected diseases and appropriate balance between the cost, time, throughput, and deep coverage, especially for low-income countries such as Iran To note, utilizing TGS panel is suitable to detect mutations, especially in communities with high numbers of consanguineous marriages such as Iran. In this country, the prevalence rate of consanguineous marriage is approximately seen in Moreover, the samples from patients without a definite diagnosis would be recommended to be analyzed by genome sequencing or exome sequencing. Integration of clinical and laboratory workflows to optimize hepatic glycogen storage disease diagnosis The present work revealed unexpected findings for two patients. However, in previous studies, reported manifestations had been less severe and essentially heart-specific, non-lysosomal glycogenosis, and mild-to-severe cardiac hypertrophy, enhancing the risk of sudden cardiac death in midlife without liver involvement 27 , This was the first patient with PRKAG2 gene mutation reported to have liver cirrhosis; however, a functionality of the novel variant remains underdiagnosed. Another patient no. These two patients had atypical clinicopathological features, precluding accurate classification and diagnosis with clinicopathological features and in need of more specific genetic testing for definite diagnosis. Despite genetic homogeneity, we found evidence of unusual features with novel variants. A possible reason for the high rate of novel variations we saw might be the lack of molecular genetic analysis before. It is known that mutations can have a specific race as well as restricted geographical or ethnical distribution, while was never analyzed such patients in our country. In addition, the results of this study will help improve gene variant spectrum, diagnostic panels, clinical diagnosis, and patient management not only in this country but also in the region. A deeper knowledge of genomic variants also leads to better findings of determinants associated with the genotype—phenotype match in GSDs In conclusion, the study indicated the benefits of TGS method in diagnosing GSD, especially when the clinical findings were equivocal. Given the cost- and time-efficiency of these methods, they can prevent the patients from receiving long-term improper treatments. The diagnosis of the patients reported here has helped expand the genetic and phenotypic spectrum of the GSDs disorders. From March to December , a total number of 14 pediatric patients suspected to GSDs who presented with hepatomegaly, hypoglycemia, growth and development delay during childhood were selected at Shiraz Transplant Research Center STRC and Namazi Hospital Shiraz, Iran. None of these 14 cases had molecular diagnoses. All the patients had already have liver biopsies with histopathological features, which suggested hepatic GSDs by the pathologist Liver biopsy was performed to determine the details of the liver pathology especially stage of fibrosis. Two independent research team members reviewed electronic and paper charts for clinical features, biochemical investigations, histopathological results, and diagnostic imaging. Whole blood samples were collected from all study subjects and sent to the Pediatric Metabolic Diseases Laboratory, Gazi Hospital Ankara, Turkey for targeted NGS-based panel analysis. The Ethics Committee of Shiraz University of Medical Sciences also approved this study Approval : IR. S , which was in accordance with the Declaration of Helsinki. In brief, genomic DNA from 2 ml peripheral blood was extracted using AutoMate Express Nucleic Acid Extraction System Life Technologies, Guilford, CT, South San Francisco, CA, US. They were also hybridized and enriched for TGS. Then, Ion Torrent S5 platform was employed for DNA sequencing analysis. A custom-targeted Ion AmpliSeq panel that included amplicons covering genes associated with Inborn Metabolic Diseases was used. Among genes, the GSD genes were also present in this panel which included the genes for Glycogen Storage Disorders with hepatic involvement such as G6PC Type Ia , SLC37A4 Type Ib , AGL Type III , GBE1 Type IV , PYGL Type VI , PHKA2 Type IXa , PHKB Type IXb , PHKG2 Type IXc and GLUT2 Type XI. The other genes for gluconeogenesis, namely PC Pyruvate Carboxylase deficiency , PCK2 Phosphoenolpyruvate carboxykinase deficiency and FBP1 Fructose-1,6-bisphosphatase , were also present in this panel. Analyses were done using an Ion Torrent chip Life Technologies, Guilford, CT, South San Francisco, CA. The results were analyzed with Ion Reporter Software Life Technologies, Guilford, CT, South San Francisco, CA, US as well as Integrated Genomic Viewer The human genome 19 was also used as the reference. Polymorphism Phenotyping v2 PolyPhen2 , Scale-Invariant Feature Transform SIFT , and MutationTaster were further employed for in silico analysis. Genomic Evolutionary Rate Profiling GERP and the Phastcons scores were also utilized to evaluate the conservation of the variants. The population frequency of each variation was correspondingly estimated using the data from the Genome Aggregation Database gnomAD and Iranome database The American College of Medical Genetics and Genomics ACMG guidelines were additionally used for variant interpretations The sequence variants were also described according to the Human Genome Variation Society Nomenclature Accession number of the relevant reference sequence s of GSD genes are presented in Supplementary File 1. Direct Sanger sequencing was performed in all subjects for validation of the causal mutations in candidate genes. Primers were designed using OLIGO primers design v. All patients had undergone ultrasound-guided liver biopsy using the standard Tru-Cut biopsy needles. All the slides were reviewed by an expert hepatopathologist B. Data were analyzed using SPSS Continuous data were presented as the mean and standard deviation SD or median and range. The study was approved by the Bioethics Committee of the Medical University of Shiraz, Iran No. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions. Hicks, J. Glycogen storage diseases: a brief review and update on clinical features, genetic abnormalities, pathologic features, and treatment. Article PubMed Google Scholar. Burda, P. Hepatic glycogen storage disorders: what have we learned in recent years?. Care 18 , 15— Article Google Scholar. Vega, C. et al. Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing. Article CAS PubMed Google Scholar. Wang, J. Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin. Chen, Y. Glycogen Storage Diseases McGraw-Hill, Google Scholar. Beyzaei, Z. Molecular diagnosis of glycogen storage disease type I: a review. EXCLI J. PubMed PubMed Central Google Scholar. Ng, S. Exome sequencing identifies the cause of a mendelian disorder. Boycott, M. Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nicastro, E. Next generation sequencing in pediatric hepatology and liver transplantation. Liver Transpl. Capture-based high-coverage NGS: a powerful tool to uncover a wide spectrum of mutation types. Targeted capture and massively parallel sequencing of twelve human exomes. Nature , — Article CAS ADS PubMed PubMed Central Google Scholar. Sentner, C. Mutation analysis in glycogen storage disease type III patients in the Netherlands: novel genotype-phenotype relationships and five novel mutations in the AGL gene. JIMD Rep. Lucchiari, S. Molecular characterisation of GSD III subjects and identification of six novel mutations in AGL. Crushell, E. Glycogen storage disease type III in the Irish population. JIMD 33 , S PubMed Google Scholar. Magoulas, P. Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review. Brown, L. Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children. JIMD 38 , — Li, C. PHKG2 mutation spectrum in glycogen storage disease type IXc: a case report and review of the literature. Burwinkel, B. Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis. Bali, D. Variability of disease spectrum in children with liver phosphorylase kinase deficiency caused by mutations in the PHKG2 gene. Retterer, K. Clinical application of whole-exome sequencing across clinical indications. Roscher, A. The natural history of glycogen storage disease types VI and IX: long-term outcome from the largest metabolic center in Canada. Rodríguez-Jiméneza, C. A new variant in PHKA2 is associated with glycogen storage disease type IXa. Jones, M. Targeted polymerase chain reaction-based enrichment and next generation sequencing for diagnostic testing of congenital disorders of glycosylation. Article CAS PubMed PubMed Central Google Scholar. Diagnosis of hepatic glycogen storage disease patients with overlapping clinical symptoms by massively parallel sequencing: a systematic review of literature. Orphanet J. Rare Dis. Article PubMed PubMed Central Google Scholar. Smith, H. Clinical application of genome and exome sequencing as a diagnostic tool for pediatric patients: a scoping review of the literature. Saadat, M. Consanguineous marriage in Iran. Fatal congenital heart glycogenosis caused by a recurrent activating RQ mutation in the g2-subunit of AMP-activated protein kinase PRKAG2 , not by phosphorylase kinase deficiency. Gilbert-Barness, E. Metabolic cardiomyopathy and conduction system defects in children. CAS PubMed Google Scholar. Richter, S. The dramatic improvement in their lives was unexpected. The rare and deadly genetic liver disorder, GSD type Ia, affects children from infancy through adulthood, causing dangerously low blood sugar levels and constant dependence on glucose consumption in the form of cornstarch every few hours for survival. If a cornstarch dose is missed, the disease can lead to seizures and even death. One year after patient Jerrod Watts first received the GSD vaccine during a minute infusion, he is completely off of cornstarch. In addition to totally stopping daily cornstarch consumption, Watts has experienced normal regulation of his blood glucose levels, weight loss, increased muscle strength, and marked improvement in his energy. Missed cornstarch doses no longer are resulting in hypoglycemia, which previously could have been life threatening. The clinical trial, conducted in conjunction with the biopharmaceutical company Ultragenyx , originally set out to simply test the safety and dosage of the gene therapy for three patients with GSD Type Ia. The gene therapy works by delivering a new copy of a gene to the liver via a naturally occurring virus. They can now go through the night without any treatment and they wake up clinically well. Prior to the treatment, Watts was consuming more than grams of cornstarch per day. One of the biggest reliefs from this gene therapy is I can now sleep through the night without worrying about dying in the middle of the night. I wake up 6 to 7 hours later with normal blood sugar. In addition to Watts, two other clinical trial cohort patients are seeing promising results on the lower cornstarch daily regimens. All three will participate in the next phase — a 4-year follow-up clinical trial study. In addition, three patients are enrolled in clinical trial testing a higher gene therapy dose. GSD Type Ia, affects an estimated 6, patients worldwide, which is caused by a defective gene for the enzyme glucosephosphatase-α G6Pase-α that controls sugar release from the liver. The condition was almost always fatal until , when it was discovered that continuous glucose therapy could help these patients. |
| Glycogen Storage Disease (GSD) and Disorders of Glucose Metabolism Panel | For questions about scheduling or research, please email Heather Saavedra at heather. saavedra uth. edu or call Glycogen Storage Disease Clinic Our goal is to improve quality of life for families and individuals with all types of glycogen storage disease GSD. Director David Rodriguez-Buritica, MD Physicians Paul Hillman, MD Dietitians Heather Saavedra, MS, RD, LD Paige Roberts, MS, RD, LD Genetic Counselor Katie Gunther, MS, CGC Medical Assistant Nancy Lomas, MA Research Coordinator Ifeoma Ibekwe Office Hours: 7 am — 4 pm CST Clinic Days: The GSD Clinic is held on the third Monday of every month. Clinic Location: The UT Professional Building Fannin St. Links: Agsdus. org Agsd. uk Curegsd. This causes abnormal amounts of glycogen to build up in certain tissues. When glycogen is not broken down properly, it leads to low blood sugar. Von Gierke disease is inherited, which means it is passed down through families. If a person has this disease, test results will show low blood sugar and high levels of lactate produced from lactic acid , blood fats lipids , and uric acid. The goal of treatment is to avoid low blood sugar. Eat frequently during the day, especially foods that contain carbohydrates starches. Older children and adults may take cornstarch by mouth to increase their carbohydrate intake. In some children, a feeding tube is placed through their nose into the stomach throughout the night to provide sugars or uncooked cornstarch. The tube can be taken out each morning. Alternatively, a gastrostomy tube G-tube can be placed to deliver food directly to the stomach overnight. A medicine to lower uric acid in the blood and decrease the risk for gout may be prescribed. Your provider may also prescribe medicines to treat kidney disease, high lipids, and to increase the cells that fight infection. People with von Gierke disease cannot properly break down fruit or milk sugar. It is best to avoid these products. More information and support for people with von Gierke disease and their families can be found at:. Association for Glycogen Storage Disease -- www. With treatment, growth, puberty, and quality of life have improved for people with von Gierke disease. Those who are identified and carefully treated at a young age can live into adulthood. Contact your provider if you have a family history of glycogen storage disease or early infant death due to low blood sugar. Couples who wish to have a baby may seek genetic counseling and testing to determine their risk for passing on von Gierke disease. Bonnardeaux A, Bichet DG. Inherited disorders of the renal tubule. In: Yu ASL, Chertow GM, Luyckx VA, Marsden PA, Taal MW, Skorecki K, eds. Brenner and Rector's The Kidney. Philadelphia, PA: Elsevier; chap Kishnani PS, Chen Y-T. Defects in metabolism of carbohydrates. In: Kliegman RM, St. Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM, eds. Nelson Textbook of Pediatrics. Litwack G. Glycogen and glycogenolysis. In: Litwack G, ed. |
| Glycogen Storage Diseases | Myogenic hyperuricemia. A deeper knowledge of genomic variants also leads to better findings of determinants associated with the genotype—phenotype match in GSDs Diagnosis of hepatic glycogen storage disease patients with overlapping clinical symptoms by massively parallel sequencing: a systematic review of literature. Published : 29 March The survival benefit of liver transplantation. Haller RG, Vissing J, Functional evaluation of metabolic myopathy. As individuals with GSD III continue to have a better quality of life and live longer, it is possible that the incidence both of ESLD and HCC will also increase, thereby resulting in greater demands on liver transplant services. |
Genetic counseling for glycogen storage disease -
Her liver biopsy also suggested unclassified GSD with marked fibrosis. Using TGS, a novel homozygous missense variant, c. GluGly , was detected in PYGL gene, indicating GSD-VI Table 2. Para-clinical results also showed increased TG, TChol, BCR, AST, and ALT Table 1.
Histopathological studies of his liver biopsy also suggested GSD-I or III with mild fibrosis. However, a homozygous pathogenic deletion variant, c. Asp77del , was detected in the liver isoform glycogen phosphorylase, the PYGL gene Table 2 Her liver biopsy also showed unclassified GSD with fibrosis.
A homozygous pathogenic variant, c. Arg44Ter , was additionally detected in a PHKG2 gene by TGS. This missense mutation had been previously reported in patients with GSD-IXc 17 , 18 , The results of liver histopathological studies also showed unclassified GSD with bridging fibrosis.
Using TGS analysis additionally revealed a novel heterozygous variant, c. Leu45His , in the glycogen phosphorylase kinase regulatory sub-unit beta gene, PHKB GSD-IXb. No other pathogenic variants were detected in other GSD genes in the panel. She was referred because of poor feeding at the age of 3.
Laboratory investigations also showed elevated TG, TChol, LDH, Alb, AST, and ALT, as well as leukopenia and acidosis Table 1. The liver biopsy revealed unclassified GSD, and moderate periportal fibrosis.
She harbored three novel variants, namely one heterozygote variant c. LeuPhe in the SLC37A4 gene and two homozygote variants c. and c. GlnArg in the PHKB gene. The pathogenic novel variant, c. As a result, she was most probably suffering from IXb, whose symptoms tended to appear with increasing age.
Histopathological studies of his liver biopsy also suggested unclassified GSD, with cirrhosis. Using TGS, a novel heterozygous variant, c. Arg5His , was detected in phosphoglycerate mutase gene, the PGAM2 GSD-X. To note, GSD-X is an autosomal recessive disorder and the detection of a single heterozygous variant did not confirm the diagnosis.
Nevertheless, lack of a second pathogenic allele or any identified pseudo-deficiency variant had left the molecular diagnosis of this patient in question. Pulmonary hypertension, moderate mitral regurgitation, and mild tricuspid regurgitation were also observed. Moreover, the liver biopsy results revealed cirrhosis, which was suggestive of unclassified GSD.
A novel heterozygous variant, c. MetLeu , was further detected in the PRKAG2 gene by TGS and implied PRKAG2 deficiency i. GSD of heart—lethal congenital. Since the PRKAG2 deficiency is an autosomal dominant inheritance with full penetrance, single heterozygote variants could confirm all of her clinical, molecular, and biochemical results.
The diagnosis of none of the GSD and non-GSD-associated genes was confirmed in patient no. She was a 2-year-old girl, who presented with hepatomegaly, clubbed fingers, failure to thrive, diarrhea, vomiting, as well as high platelet count, AST, ALT and low uric acid Table 1.
Her liver biopsy was suggestive of GSD or lipid storage disease with mild fibrosis. No deleterious mutations were also detected in any of the related GSD genes analyzed.
There was, therefore, no definite diagnosis for this patient. In five patients, the features of liver histopathology were suggestive of unclassified GSD, molecular genetic investigations of these patients which confirmed the diagnosis of GSD-VI in one patient no.
In one case, not only the features of liver histopathology were shown ambiguous results, but also no deleterious mutations were detected in any of the GSD genes analyzed no. Classification and sub-typing of GSD patients are important steps towards personalized patient management, which can help clinicians practice the best and the most correct therapy with the fewest adverse events for patients Here, the first and largest cohort is reported about GSD sub-typing from the Middle East and Asia.
It is also the first study, addressing clinical characteristics and genomics in sub-typing of patients with GSDs from Iranian population.
In this cohort of 14 pediatric patients, 10 novel pathogenic variants in the SLC37A , AGL , GBE1 , PHKB , PGAM2 and PRKAG2 genes were found. Notably, GSD-IX was detected in three patients, which had not been reported from Iran, so far.
It means that it has been overlooked in our population because of subtle patient presentations and self-limited outcomes as well as lack of molecular diagnosis analyses. Therefore, it has been classified as other types of GSD, such as GSD-III or VI.
Chronic liver diseases, such as cirrhosis and fibrosis, have been also rarely reported in some types of GSDs e. GSD-VI and IX In addition, asymptomatic heart problems with liver involvement were identified in a GSD of the heart-lethal congenital disorder i.
PRKAG2 deficiency in one patient in our study cohort. To the best of our knowledge, we report for the first time liver cirrhosis in GSD-X and GSD of the heart-lethal congenital i.
PRKAG2 deficiency. In this pathological report, 13 patients were suggestive to have one type of GSD without exact sub-typing, so molecular genetic analysis namely, targeted genome sequencing based on NGS was performed, confirming the exact type of GSD.
According to these results, molecular genetic testing, especially NGS-based GSD or inborn inherited metabolic panel exome sequencing, was recommended for definite diagnosis of GSD sub-types prior to invasive liver biopsy. Liver histopathology may also be a powerful and effective method for monitoring long-term liver complications and evaluating the status of the liver in these patients, but not for confirming diagnosis and accurate sub-typing.
NGS-based targeted exome sequencing is thus reported as the best future routine method of molecular diagnosis. This is especially useful for complex disorders with less specific clinical findings Nevertheless, in defining the syndromes or diseases like GSD, clinical features or biochemical phenotypes can effectively address a particular pathway or a group of genes responsible for the disease.
In such cases, a custom-targeted gene-sequencing panel has been confirmed to be an efficient as well as time- and cost-effective technique with high diagnostic yields Analytical workflows for the diagnosis of GSD diseases are not fully standardized; however, a useful and practical approach based on clinical and biochemical evaluations followed by targeted molecular analysis was reported later, as shown in Fig.
Moreover, using custom-target sequencing vs. exome sequencing would become a routine technique due to the focus on a limited number of suspected diseases and appropriate balance between the cost, time, throughput, and deep coverage, especially for low-income countries such as Iran To note, utilizing TGS panel is suitable to detect mutations, especially in communities with high numbers of consanguineous marriages such as Iran.
In this country, the prevalence rate of consanguineous marriage is approximately seen in Moreover, the samples from patients without a definite diagnosis would be recommended to be analyzed by genome sequencing or exome sequencing.
Integration of clinical and laboratory workflows to optimize hepatic glycogen storage disease diagnosis The present work revealed unexpected findings for two patients.
However, in previous studies, reported manifestations had been less severe and essentially heart-specific, non-lysosomal glycogenosis, and mild-to-severe cardiac hypertrophy, enhancing the risk of sudden cardiac death in midlife without liver involvement 27 , This was the first patient with PRKAG2 gene mutation reported to have liver cirrhosis; however, a functionality of the novel variant remains underdiagnosed.
Another patient no. These two patients had atypical clinicopathological features, precluding accurate classification and diagnosis with clinicopathological features and in need of more specific genetic testing for definite diagnosis. Despite genetic homogeneity, we found evidence of unusual features with novel variants.
A possible reason for the high rate of novel variations we saw might be the lack of molecular genetic analysis before. It is known that mutations can have a specific race as well as restricted geographical or ethnical distribution, while was never analyzed such patients in our country.
In addition, the results of this study will help improve gene variant spectrum, diagnostic panels, clinical diagnosis, and patient management not only in this country but also in the region. A deeper knowledge of genomic variants also leads to better findings of determinants associated with the genotype—phenotype match in GSDs In conclusion, the study indicated the benefits of TGS method in diagnosing GSD, especially when the clinical findings were equivocal.
Given the cost- and time-efficiency of these methods, they can prevent the patients from receiving long-term improper treatments.
The diagnosis of the patients reported here has helped expand the genetic and phenotypic spectrum of the GSDs disorders.
From March to December , a total number of 14 pediatric patients suspected to GSDs who presented with hepatomegaly, hypoglycemia, growth and development delay during childhood were selected at Shiraz Transplant Research Center STRC and Namazi Hospital Shiraz, Iran.
None of these 14 cases had molecular diagnoses. All the patients had already have liver biopsies with histopathological features, which suggested hepatic GSDs by the pathologist Liver biopsy was performed to determine the details of the liver pathology especially stage of fibrosis.
Two independent research team members reviewed electronic and paper charts for clinical features, biochemical investigations, histopathological results, and diagnostic imaging.
Whole blood samples were collected from all study subjects and sent to the Pediatric Metabolic Diseases Laboratory, Gazi Hospital Ankara, Turkey for targeted NGS-based panel analysis. The Ethics Committee of Shiraz University of Medical Sciences also approved this study Approval : IR.
S , which was in accordance with the Declaration of Helsinki. In brief, genomic DNA from 2 ml peripheral blood was extracted using AutoMate Express Nucleic Acid Extraction System Life Technologies, Guilford, CT, South San Francisco, CA, US.
They were also hybridized and enriched for TGS. Then, Ion Torrent S5 platform was employed for DNA sequencing analysis. A custom-targeted Ion AmpliSeq panel that included amplicons covering genes associated with Inborn Metabolic Diseases was used. Among genes, the GSD genes were also present in this panel which included the genes for Glycogen Storage Disorders with hepatic involvement such as G6PC Type Ia , SLC37A4 Type Ib , AGL Type III , GBE1 Type IV , PYGL Type VI , PHKA2 Type IXa , PHKB Type IXb , PHKG2 Type IXc and GLUT2 Type XI.
The other genes for gluconeogenesis, namely PC Pyruvate Carboxylase deficiency , PCK2 Phosphoenolpyruvate carboxykinase deficiency and FBP1 Fructose-1,6-bisphosphatase , were also present in this panel.
Analyses were done using an Ion Torrent chip Life Technologies, Guilford, CT, South San Francisco, CA. The results were analyzed with Ion Reporter Software Life Technologies, Guilford, CT, South San Francisco, CA, US as well as Integrated Genomic Viewer The human genome 19 was also used as the reference.
Polymorphism Phenotyping v2 PolyPhen2 , Scale-Invariant Feature Transform SIFT , and MutationTaster were further employed for in silico analysis.
Genomic Evolutionary Rate Profiling GERP and the Phastcons scores were also utilized to evaluate the conservation of the variants. The population frequency of each variation was correspondingly estimated using the data from the Genome Aggregation Database gnomAD and Iranome database The American College of Medical Genetics and Genomics ACMG guidelines were additionally used for variant interpretations The sequence variants were also described according to the Human Genome Variation Society Nomenclature Accession number of the relevant reference sequence s of GSD genes are presented in Supplementary File 1.
Direct Sanger sequencing was performed in all subjects for validation of the causal mutations in candidate genes.
Primers were designed using OLIGO primers design v. All patients had undergone ultrasound-guided liver biopsy using the standard Tru-Cut biopsy needles. All the slides were reviewed by an expert hepatopathologist B. Data were analyzed using SPSS Continuous data were presented as the mean and standard deviation SD or median and range.
The study was approved by the Bioethics Committee of the Medical University of Shiraz, Iran No. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions. Hicks, J.
Glycogen storage diseases: a brief review and update on clinical features, genetic abnormalities, pathologic features, and treatment.
Article PubMed Google Scholar. Burda, P. Hepatic glycogen storage disorders: what have we learned in recent years?. Care 18 , 15— Article Google Scholar.
Vega, C. et al. Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing. Article CAS PubMed Google Scholar. Wang, J. Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin.
Chen, Y. Glycogen Storage Diseases McGraw-Hill, The clinical trial originally set out to simply test the safety and dosage of the gene therapy for three patients with GSD Type Ia. The dramatic improvement in their lives was unexpected.
The rare and deadly genetic liver disorder, GSD type Ia, affects children from infancy through adulthood, causing dangerously low blood sugar levels and constant dependence on glucose consumption in the form of cornstarch every few hours for survival.
If a cornstarch dose is missed, the disease can lead to seizures and even death. One year after patient Jerrod Watts first received the GSD vaccine during a minute infusion, he is completely off of cornstarch.
In addition to totally stopping daily cornstarch consumption, Watts has experienced normal regulation of his blood glucose levels, weight loss, increased muscle strength, and marked improvement in his energy.
Missed cornstarch doses no longer are resulting in hypoglycemia, which previously could have been life threatening. The clinical trial, conducted in conjunction with the biopharmaceutical company Ultragenyx , originally set out to simply test the safety and dosage of the gene therapy for three patients with GSD Type Ia.
The gene therapy works by delivering a new copy of a gene to the liver via a naturally occurring virus. They can now go through the night without any treatment and they wake up clinically well. Prior to the treatment, Watts was consuming more than grams of cornstarch per day.
Our goal is to improve quality of life for families and individuals with all types of glycogen storage disease GSD. We utilize a comprehensive approach for diagnosis, management and long-term follow up of children and adults with GSD. We utilize state of the art management tools, such as continuous glucose monitoring, point of care glucose and blood ketone monitoring to help further individualize clinical management.
We follow, and have extensive experience with a large number of individuals with GSD Ia from South Texas and Northern Mexico. Additionally, we assist other healthcare providers with the diagnosis and management of carbohydrate metabolism disorders, including liver and muscular forms of GSD.
Our medical team is led by David Rodriguez-Buritica, MD who is board certified in Medical Genetics and Pediatric Endocrinology with experience in diagnosis and medical management of individuals with carbohydrate metabolism disorders, and our clinic is staffed by registered metabolic nutritionist, led by Heather Saavedra, MS, RD, LD, to assist those affected by these disorders developing a diet plan to meet individual goals.
Our websites may use cookies to gycogen and Immune support tablets your experience. By continuing without changing your cookie settings, you agree to storave Genetic counseling for glycogen storage disease. For more counseeling, please see our University Websites Privacy Notice. September 19, Lauren Woods - Schools of Medicine and Dental Medicine. The clinical trial originally set out to simply test the safety and dosage of the gene therapy for three patients with GSD Type Ia. The dramatic improvement in their lives was unexpected. Thank glcyogen for Genettic nature. You counse,ing using a browser version with limited support diease CSS. To obtain storge best experience, we Plant-based ingredients you use a more up Genetic counseling for glycogen storage disease date browser Genetic counseling for glycogen storage disease turn off Pain management techniques mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. An Erratum to this article was published on 01 September Purpose: Glycogen storage disease type III is a rare disease of variable clinical severity affecting primarily the liver, heart, and skeletal muscle. It is caused by deficient activity of glycogen debranching enzyme, which is a key enzyme in glycogen degradation.
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Ich entschuldige mich, aber es kommt mir nicht ganz heran. Kann, es gibt noch die Varianten?
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