1,531 results match your criteria Glucose-6-Phosphatase Deficiency


Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre.

Orphanet J Rare Dis 2022 05 12;17(1):195. Epub 2022 May 12.

Inherited Metabolic Diseases, Evelina London Children's Hospital, London, SE1 7EH, UK.

Background: Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG6P) within neutrophils. Treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, is a novel therapy that reduces 1,5-anhydroglucitol (1,5AG) in plasma. Read More

View Article and Full-Text PDF

Molecular mechanisms of aberrant neutrophil differentiation in glycogen storage disease type Ib.

Cell Mol Life Sci 2022 Apr 18;79(5):246. Epub 2022 Apr 18.

Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong, 339-700, Republic of Korea.

Glycogen storage disease type Ib (GSD-Ib), characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction, is caused by a deficiency in glucose-6-phosphate transporter (G6PT). Neutropenia in GSD-Ib has been known to result from enhanced apoptosis of neutrophils. However, it has also been raised that neutrophil maturation arrest in the bone marrow would contribute to neutropenia. Read More

View Article and Full-Text PDF

Liver transplantation in glycogen storage disease: a single-center experience.

Orphanet J Rare Dis 2022 03 21;17(1):127. Epub 2022 Mar 21.

Shiraz Transplant Research Center (STRC), Shiraz University of Medical Sciences, Khalili St., Research Tower, Seventh Floor, Shiraz, Iran.

Background: Glycogen storage diseases (GSDs) are inherited glycogen metabolic disorders which have various subtypes. GSDs of type I, III, IV, VI, and IX show liver involvement and are considered as hepatic types of GSDs. Thus, liver transplantation (LT) has been proposed as a final therapy for these types of GSD. Read More

View Article and Full-Text PDF

Serum sex hormone-binding globulin levels are reduced and inversely associated with intrahepatic lipid content and saturated fatty acid fraction in adult patients with glycogen storage disease type 1a.

J Endocrinol Invest 2022 Jun 7;45(6):1227-1234. Epub 2022 Feb 7.

Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Maastricht University Medical Centre, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.

Purpose: De novo lipogenesis has been inversely associated with serum sex hormone-binding globulin (SHBG) levels. However, the directionality of this association has remained uncertain. We, therefore, studied individuals with glycogen storage disease type 1a (GSD1a), who are characterized by a genetic defect in glucose-6-phosphatase resulting in increased rates of de novo lipogenesis, to assess the downstream effect on serum SHBG levels. Read More

View Article and Full-Text PDF

Secondary diabetes as a rare complication of glycogen storage disease 1a: case report and review of literature.

Pediatr Endocrinol Diabetes Metab 2021 ;27(4):283-286

Department of Endocrinology, ABVIMS & Dr Ram Manohar Lohia Hospital, India.

Glycogen storage diseases (GSDs) are disorders of carbohydrate metabolism and hypoglycemia is their hallmark. Secondary diabetes with glycogen storage disease, which seems rather paradoxical, has been rarely reported. A 13-year-old girl previously diagnosed to have GSD 1a presented to the emergency with multiple episodes of vomiting and loss of consciousness. Read More

View Article and Full-Text PDF
February 2022

Exosomal MicroRNAs as Potential Biomarkers of Hepatic Injury and Kidney Disease in Glycogen Storage Disease Type Ia Patients.

Int J Mol Sci 2021 Dec 28;23(1). Epub 2021 Dec 28.

Laboratory of Molecular Biology, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy.

Glycogen storage disease type Ia (GSDIa) is an inherited metabolic disorder caused by mutations in the enzyme glucose-6-phosphatase-α (G6Pase-α). Affected individuals develop renal and liver complications, including the development of hepatocellular adenoma/carcinoma and kidney failure. The purpose of this study was to identify potential biomarkers of the evolution of the disease in GSDIa patients. Read More

View Article and Full-Text PDF
December 2021

Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan.

J Pediatr Endocrinol Metab 2022 Mar 6;35(3):373-385. Epub 2022 Jan 6.

Department of Paediatrics & Child Health, The Aga Khan University (AKU) Hospital, Karachi, Pakistan.

Objectives: Evaluation of clinical, biochemical and molecular analysis of Pakistani patients with hepatic GSDs.

Methods: Medical charts, biochemical, histopathological and molecular results of patients with hepatic GSD were reviewed.

Results: Out of 55 GSD patients, 41 (74. Read More

View Article and Full-Text PDF

Biophysical and functional properties of purified glucose-6-phosphatase catalytic subunit 1.

J Biol Chem 2022 01 21;298(1):101520. Epub 2021 Dec 21.

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.

Glucose-6-phosphatase catalytic subunit 1 (G6PC1) plays a critical role in hepatic glucose production during fasting by mediating the terminal step of the gluconeogenesis and glycogenolysis pathways. In concert with accessory transport proteins, this membrane-integrated enzyme catalyzes glucose production from glucose-6-phosphate (G6P) to support blood glucose homeostasis. Consistent with its metabolic function, dysregulation of G6PC1 gene expression contributes to diabetes, and mutations that impair phosphohydrolase activity form the clinical basis of glycogen storage disease type 1a. Read More

View Article and Full-Text PDF
January 2022

Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs.

Nutrients 2021 Oct 27;13(11). Epub 2021 Oct 27.

Department of Pediatrics, Division of Pediatric Endocrinology, Montreal Children's Hospital, McGill University Health Center, Montreal, QC H4A 3J1, Canada.

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Read More

View Article and Full-Text PDF
October 2021

Glycogen Storage Disease Type Ia Screening Using Dried Blood Spots on Filter Paper: Application of COP-PCR for Detection of the c.648G>T G6PC Gene Mutation.

Kobe J Med Sci 2021 Nov 2;67(2):E71-E78. Epub 2021 Nov 2.

Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

Glycogen storage disease type Ia (GSDIa, OMIM #232200) is an autosomal recessive metabolic disease characterized by impaired glucose homeostasis and has a long-term complication of hepatocellular adenoma/carcinoma. GSDIa is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). Recent studies have suggested that early treatment by gene replacement therapy may be a good solution to correct the glucose metabolism and prevent serious late complications. Read More

View Article and Full-Text PDF
November 2021

Sensorineural hearing loss in GSD type I patients. A newly recognized symptomatic association of potential clinical significance and unclear pathomechanism.

Int J Pediatr Otorhinolaryngol 2021 Dec 10;151:110970. Epub 2021 Nov 10.

Department of Pathology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland.

Objective: Glycogen storage disease (GSD) type I is an inborn error of carbohydrates metabolism characterized by inability to convert glucose-6-phosphate to glucose. It presents with serious liver and metabolic complications, as well as in type Ib with severe infections due to neutropenia. So far, the sensorineural hearing impairment has not been reported in these patients. Read More

View Article and Full-Text PDF
December 2021

Untargeted plasma metabolomics identifies broad metabolic perturbations in glycogen storage disease type I.

J Inherit Metab Dis 2022 03 10;45(2):235-247. Epub 2021 Nov 10.

Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background: The metabolic defect in glycogen storage disease type I (GSDI) results in fasting hypoglycemia and typical secondary metabolic abnormalities (eg, hypertriglyceridemia, hyperlactatemia, hyperuricemia). The aim of this study was to assess further perturbations of the metabolic network in GSDI patients under ongoing treatment.

Methods: In this prospective observational study, plasma samples of 14 adult patients (11 GSDIa, 3 GSDIb. Read More

View Article and Full-Text PDF

Modifiable factors affecting renal preservation in type I glycogen storage disease after liver transplantation: a single-center propensity-match cohort study.

Orphanet J Rare Dis 2021 10 11;16(1):423. Epub 2021 Oct 11.

Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.

Background And Aims: Glycogen storage disease type I (GSD-I) is an autosomal recessive disorder of carbohydrate metabolism, resulting in limited production of glucose and excessive glycogen storage in the liver and kidneys. These patients are characterized by life-threatening hypoglycemia, metabolic derangements, hepatomegaly, chronic kidney disease, and failure to thrive. Liver transplantation (LT) has been performed for poor metabolic control and delayed growth. Read More

View Article and Full-Text PDF
October 2021

Glycogen storage disease type I patients with hyperlipidemia have no signs of early vascular dysfunction and premature atherosclerosis.

Nutr Metab Cardiovasc Dis 2021 11 13;31(12):3384-3392. Epub 2021 Aug 13.

Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany. Electronic address:

Background And Aims: Glycogen storage disease type I (GSD I) is associated with hyperlipidemia, a known risk factor for premature atherosclerosis. Few studies have addressed endothelial dysfunction in patients with GSD I, and these studies yielded controversial results.

Methods And Results: We investigated vascular dysfunction in a cohort of 32 patients with GSD I (26 GSD Ia, 6 GSD Ib, mean age 20. Read More

View Article and Full-Text PDF
November 2021

Cellular and metabolic effects of renin-angiotensin system blockade on glycogen storage disease type I nephropathy.

Hum Mol Genet 2022 03;31(6):914-928

Université Claude Bernard Lyon 1, Université de Lyon, INSERM UMR-S1213, Lyon 69008, France.

Glycogen Storage Disease Type I (GSDI) is an inherited disease caused by glucose-6 phosphatase (G6Pase) deficiency, leading to a loss of endogenous glucose production and severe hypoglycemia. Moreover, most GSDI patients develop a chronic kidney disease (CKD) due to lipid accumulation in the kidney. Similar to diabetic CKD, activation of renin-angiotensin system (RAS) promotes renal fibrosis in GSDI. Read More

View Article and Full-Text PDF

Impact of glycogen storage disease type I on adult daily life: a survey.

Orphanet J Rare Dis 2021 09 3;16(1):371. Epub 2021 Sep 3.

Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, University of Freiburg, Faculty of Medicine, Mathildenstraße 1, 79106, Freiburg, Germany.

Background: Glycogen storage disease type I (GSD I) is a rare autosomal recessive disorder of carbohydate metabolism characterized by recurrent hypoglycaemia and hepatomegaly. Management of GSD I is demanding and comprises a diet with defined carbohydrate intake and the use of complex carbohydrates, nocturnal tube feeding or night-time uncooked cornstarch intake, regular blood glucose monitoring and the handling of emergency situations. With improved treatment, most patients nowadays survive into adulthood. Read More

View Article and Full-Text PDF
September 2021

A Multidisciplinary Approach for Tophi Wounds Caused by Glycogen Storage Disease Type 1a: A Rare Case.

Adv Skin Wound Care 2021 Sep;34(9):1-5

At the Wound Care Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Jiangsu, China, Min Wei, MS, is an enterostomal therapist; Jian Li, BS, is a specialist wound care nurse; Dongyun Xia, BS, is a specialist wound care nurse; and Shaojing Zhou, BS, is a wound care nurse. Shanmei Shen, MS, is an endocrinologist, Department of Endocrinology. Siyuan Wen, MS, is a surgeon, Department of Orthopedics. Guanchun Zhao, BS, is a physical therapist, Department of Rehabilitation. Acknowledgment: This work was supported in part by the Jiangsu Provincial Hospital Management Innovation Research Project (JSYGY-3-2020-31). The authors have disclosed no other financial relationships related to this article. Submitted March 16, 2021; accepted in revised form April 19, 2021.

Abstract: Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders caused by enzyme deficiencies in glycogen catabolism. The more common type, GSD type Ia, is caused by glucose-6-phosphatase deficiency and often complicated by gout from hyperuricemia. Here, the authors report a rare case of a tophi wound caused by GSD type Ia in a Chinese patient. Read More

View Article and Full-Text PDF
September 2021

Multidisciplinary management of pregnancy and labour in a patient with glycogen storage disease type 1a.

BMJ Case Rep 2021 Aug 11;14(8). Epub 2021 Aug 11.

Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, Salford, Greater Manchester, UK.

Glycogen storage disease type 1a (GSD 1a) is a metabolic disorder caused by deficiency of an enzyme required for glycogen breakdown, causing hypoglycaemia and lactic acidosis. Metabolic derangements cause disease manifestations affecting the kidneys, liver and platelet function. Physiological changes in pregnancy worsen fasting intolerance and increase reliance on exogenous glucose to avoid lactic acidosis. Read More

View Article and Full-Text PDF

Empagliflozin ameliorated neutropenia in a girl with glycogen storage disease Ib.

Pediatr Int 2021 Nov 11;63(11):1394-1396. Epub 2021 Aug 11.

Department of Pediatrics, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.

View Article and Full-Text PDF
November 2021

Immunological features and complications in patients with glycogen storage disease 1b after living donor liver transplantation.

Pediatr Transplant 2021 12 2;25(8):e14104. Epub 2021 Aug 2.

Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.

Background: LT is an elective treatment choice for children diagnosed with GSD1b that can improve their quality of life and stabilize their glucose intolerance. However, careful attention should be paid to immunosuppression after LT due to the susceptibility to infection because of neutropenia and neutrophil dysfunction in GSD1b patients. This study revealed the immunological features and complications in the early post-LT period. Read More

View Article and Full-Text PDF
December 2021

Infliximab treatment of glycogenosis Ib with Crohn's-like enterocolitis: A case report.

World J Clin Cases 2021 Jul;9(19):5280-5286

Pathology Department, Capital Institute of Pediatrics, Beijing 100020, China.

Background: Glycogen storage disease type Ib (GSD-Ib) is a glycogen metabolism disorder that leads to the manifestations of inflammatory bowel disease (IBD), especially Crohn's disease (CD)-like colitis. Although biological agents are effective for treating CD, their application in the treatment of GSD-Ib with CD-like colitis has been rarely reported.

Case Summary: A 13-year-old Han male was diagnosed with GSD-Ib with CD. Read More

View Article and Full-Text PDF

Crohn disease-like enterocolitis remission after empagliflozin treatment in a child with glycogen storage disease type Ib: a case report.

Ital J Pediatr 2021 Jul 2;47(1):149. Epub 2021 Jul 2.

Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.

Background: Besides major clinical/biochemical features, neutropenia and inflammatory bowel disease (IBD) constitute common complications of Glycogen storage disease type Ib (GSD Ib). However, their management is still challenging. Although previous reports have shown benefit of empagliflozin administration on neutropenia, no follow-up data on bowel (macro/microscopic) morphology are available. Read More

View Article and Full-Text PDF

Modeling Phenotypic Heterogeneity of Glycogen Storage Disease Type 1a Liver Disease in Mice by Somatic CRISPR/CRISPR-associated protein 9-Mediated Gene Editing.

Hepatology 2021 11 15;74(5):2491-2507. Epub 2021 Aug 15.

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background And Aims: Patients with glycogen storage disease type 1a (GSD-1a) primarily present with life-threatening hypoglycemia and display severe liver disease characterized by hepatomegaly. Despite strict dietary management, long-term complications still occur, such as liver tumor development. Variations in residual glucose-6-phosphatase (G6PC1) activity likely contribute to phenotypic heterogeneity in biochemical symptoms and complications between patients. Read More

View Article and Full-Text PDF
November 2021

Neurological Characteristics of Pediatric Glycogen Storage Disease.

Front Endocrinol (Lausanne) 2021 21;12:685272. Epub 2021 May 21.

Faculdades Pequeno Príncipe, Curitiba, Brazil.

Glycogen storage diseases (GSD) encompass a group of rare inherited diseases due dysfunction of glycogen metabolism. Hypoglycemia is the most common primary manifestation of GSD, and disturbances in glucose metabolism can cause neurological damage. The aims of this study were to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. Read More

View Article and Full-Text PDF
January 2022

Hepatocyte-specific glucose-6-phosphatase deficiency disturbs platelet aggregation and decreases blood monocytes upon fasting-induced hypoglycemia.

Mol Metab 2021 11 4;53:101265. Epub 2021 Jun 4.

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address:

Objective: Glycogen storage disease type 1a (GSD Ia) is a rare inherited metabolic disorder caused by mutations in the glucose-6-phosphatase (G6PC1) gene. When untreated, GSD Ia leads to severe fasting-induced hypoglycemia. Although current intensive dietary management aims to prevent hypoglycemia, patients still experience hypoglycemic events. Read More

View Article and Full-Text PDF
November 2021

A triple-blinded crossover study to evaluate the short-term safety of sweet manioc starch for the treatment of glycogen storage disease type Ia.

Orphanet J Rare Dis 2021 06 3;16(1):254. Epub 2021 Jun 3.

Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal Do Rio Grande Do Sul, Ramiro Barcelos St., 2350, Porto Alegre, Brazil.

Background: Glycogen storage disease type 1a (GSD Ia) is characterized by severe fasting hypoglycemia. The clinical management includes the administration of uncooked cornstarch (UCCS). Although such a diet approach is effective in achieving euglycemia, its impact on the quality of life of patients should be considered. Read More

View Article and Full-Text PDF

LONG TERM MANAGEMENT OF GLYCOGEN STORAGE DISEASE TYPE 1B: A BRAZILIAN TERTIARY CENTER EXPERIENCE.

Arq Gastroenterol 2021 Jan-Mar;58(1):87-92

Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Pediatria, Campinas, SP, Brasil.

Background: Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, in addition to the well-known metabolic manifestations of GSD. Treatment with granulocyte-colony stimulating factor (G-CSF) is often indicated in the management of neutropenia and inflammatory bowel disease.

Objective: To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b), with special attention to immune-related complications. Read More

View Article and Full-Text PDF