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J Inherit Metab Dis 2020 May 31. Epub 2020 May 31.

Glycogen Storage Disease Program, Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Glycogen storage disease type Ia (GSD-Ia) is an inherited metabolic disease caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) which plays a critical role in blood glucose homeostasis by catalyzing the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate in the terminal step of glycogenolysis and gluconeogenesis. Patients with GSD-Ia manifest life-threatening fasting hypoglycemia along with the excessive accumulation of hepatic glycogen and triglycerides which results in hepatomegaly and a risk of long-term complications such as hepatocellular adenoma and carcinoma (HCA/HCC). The etiology of HCA/HCC development in GSD-Ia, however, is unknown. Read More

J Pediatr Endocrinol Metab 2020 May 21;33(6):803-808. Epub 2020 May 21.

Department of Pediatric Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Western Road, Wenzhou, Zhejiang Province, China.

Background Marked hypertriglyceridemia in infancy is extremely rare. Patients with severe hypertriglyceridemia in early life may be unmasked by a primary or secondary cause. Case presentation A female infant was born in a good condition with normal Apgar scores. Read More

Biochem Biophys Res Commun 2020 Jun 16;527(3):824-830. Epub 2020 May 16.

Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

The current phase I/II clinical trial for human glycogen storage disease type-Ia (GSD-Ia) (NCT03517085) uses a recombinant adeno-associated virus (rAAV) vector expressing a codon-optimized human glucose-6-phosphatase-α (G6Pase-α or G6PC). DNA sequence changes introduced by codon-optimization can negatively impact gene expression. We therefore generated a novel variant in which a single amino acid change, S298C, is introduced into the native human G6PC sequence. Read More

JIMD Rep 2020 Mar 29;52(1):17-22. Epub 2020 Jan 29.

APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Centre de référence des maladies héréditaires du métabolisme hépatique Clamart France.

Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disease due to glucose-6-phosphatase deficiency. Chronic kidney disease is a frequent complication that may manifest itself by glomerular lesions and tubular dysfunction from the second decade of life. We report two young GSDIa patients with malignant renal tumor. Read More

Hepatology 2020 Feb 21. Epub 2020 Feb 21.

Departments of Pediatrics and University of Groningen, University Medical Center Groningen, The Netherlands, Groningen.

Glycogen storage disease type Ia (GSD Ia) is an inborn error of metabolism caused by defective glucose-6-phosphatase (G6PC) activity. GSD Ia patients exhibit severe hepatomegaly due to glycogen and triglyceride (TG) accumulation in the liver. We have previously shown that the activity of Carbohydrate Response Element Binding Protein (ChREBP), a key regulator of glycolysis and de novo lipogenesis, is increased in GSD Ia. Read More

Orphanet J Rare Dis 2020 Feb 11;15(1):45. Epub 2020 Feb 11.

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan, College of Medicine, Seoul, Korea.

Background: Glycogen storage disease (GSD) Ia, caused by mutations in the glucose-6-phosphatase (G6PC) gene, is characterized by hepatomegaly, hypoglycemia, lactic acidosis, dyslipidemia, and hyperuricemia. This study aimed to investigate clinical and molecular features and late complications in Korean patients with GSD Ia.

Results: Fifty-four Korean patients (33 males and 21 females) from 47 unrelated families, who were diagnosed with GSD Ia, based on genetic and biochemical data, between 1999 and 2017, were included in this study. Read More

Hum Mol Genet 2020 Mar;29(5):834-844

Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Glucose-6-phosphatase-α (G6Pase-α or G6PC) deficiency in glycogen storage disease type-Ia (GSD-Ia) leads to impaired hepatic autophagy, a recycling process important for cellular metabolism and homeostasis. Autophagy can be regulated by several energy sensing pathways, including sirtuin 1 (SIRT1), forkhead box O (FoxO), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-α (PPAR-α), and mammalian target of rapamycin (mTOR). Using 10-day old global G6pc-deficient (G6pc-/-) mice, hepatic autophagy impairment was attributed to activation of mTOR and inhibition of AMPK signaling. Read More

Mol Ther Methods Clin Dev 2019 Dec 11;15:383-391. Epub 2019 Nov 11.

Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.

Glycogen storage disease type Ia (GSD Ia) is caused by mutations in the glucose-6-phosphatase (G6Pase) catalytic subunit gene (). GSD Ia complications include hepatocellular adenomas (HCA) with a risk for hepatocellular carcinoma (HCC) formation. Genome editing with adeno-associated virus (AAV) vectors containing a zinc-finger nuclease (ZFN) and a donor transgene was evaluated in adult mice with GSD Ia. Read More

Hum Mol Genet 2020 01;29(2):286-294

Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham NC 27710, USA.

Glycogen storage disease type Ia (GSD Ia) is caused by autosomal mutations in glucose-6-phosphatase α catalytic subunit (G6PC) and can present with severe hypoglycemia, lactic acidosis and hypertriglyceridemia. In both children and adults with GSD Ia, there is over-accumulation of hepatic glycogen and triglycerides that can lead to steatohepatitis and a risk for hepatocellular adenoma or carcinoma. Here, we examined the effects of the commonly used peroxisomal proliferated activated receptor α agonist, fenofibrate, on liver and kidney autophagy and lipid metabolism in 5-day-old G6pc -/- mice serving as a model of neonatal GSD Ia. Read More

Biochem Biophys Res Commun 2020 Jan 15;522(1):1-7. Epub 2019 Nov 15.

Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Hepatocellular adenoma/carcinoma (HCA/HCC) is a long-term complication of the metabolic disorder glycogen storage disease type Ia (GSD-Ia) deficient in glucose-6-phosphatase-α (G6PC or G6Pase-α). We have shown previously that hepatic G6Pase-α deficiency leads to autophagy impairment, mitochondrial dysfunction, enhanced glycolysis, and augmented hexose monophosphate shunt, all of which can contribute to hepatocarcinogenesis. However, the mechanism underlying HCA/HCC development in GSD-Ia remains unclear. Read More

Dig Dis Sci 2019 12;64(12):3440-3445

Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, Albuquerque, NM, USA.

J Inherit Metab Dis 2020 Mar 4;43(2):269-278. Epub 2019 Sep 4.

Glycogen Storage Disease Program, Connecticut Children's Medical Center, Hartford, Connecticut.

Cornstarch has been the primary treatment for glycogen storage disease type Ia (GSD Ia) for over 35 years. When cornstarch was first described as a treatment, few people survived beyond early childhood. As the prognosis for this population has improved, the need to ensure appropriate cornstarch dosing for different age groups has become imperative. Read More

Thyroid 2019 08;29(8):1158-1167

1Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore.

Glycogen storage disease type Ia (GSD Ia), also known as von Gierke disease, is the most common glycogen storage disorder. It is caused by the deficiency of glucose-6-phosphatase, the enzyme that catalyzes the final step of gluconeogenesis and glycogenolysis. The accumulation of glucose-6-phosphate leads to increased glycogen and triglyceride levels in the liver. Read More

BMC Med Genet 2019 05 20;20(1):85. Epub 2019 May 20.

Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing, 400038, China.

Background: Glycogen storage disease type I (GSD I), also known as von Gierk disease, is a metabolic disorder leading to the excessive accumulation of glycogen and fat in organs, characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, puberty delay and growth retardation, which can be indicated by height, weight, blood glucose and blood lipids.

Case Presentation: Here we present a 16-year-old male patient with GSD Ia complicated with hepatic adenoma and combined with hepatitis B. As a chronic hepatitis B patient, the patient was admitted to hospital in order to further clarify the nature of hepatic space occupancy because of suspicion of hepatocellular carcinoma. Read More

Balkan J Med Genet 2018 Dec 31;21(2):55-57. Epub 2018 Dec 31.

Department of Genetics, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey.

Glycogen storage disease type Ia (GSD1A) is caused by mutations in the gene. The gene was first cloned in 1993. Since then, many different mutations have been identified leading to this disease. Read More

Dis Model Mech 2019 04 5;12(4). Epub 2019 Apr 5.

Laboratory of Molecular Biology, Istituto Giannina Gaslini, 16147 Genova, Italy

Hepatocellular adenomas (HCAs) are benign tumors, of which the most serious complications are hemorrhage and malignant transformation to hepatocellular carcinoma (HCC). Among the various subtypes of HCA, the β-catenin-activated subtype (bHCA) is associated with greatest risk of malignant transformation. Magnetic resonance imaging (MRI) is an important tool to differentiate benign and malignant hepatic lesions, and preclinical experimental approaches may help to develop a method to identify MRI features associated with bHCA. Read More

Gene 2019 Jun 16;700:7-16. Epub 2019 Mar 16.

Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, India. Electronic address:

Background: Glycogen storage disease type-1a is an inherited, autosomal recessive disorder caused by mutations in G6PC1 gene leading to deficiency of glucose-6-phosphatase-α specifically in the liver/kidney/intestine.

Patients And Methods: DNA of six unrelated Indian GSD-1a patients were screened for mutations in the entire coding region of G6PC1 gene followed by direct DNA sequencing and functional was tested using glucose-6-phosphatase assay.

Results: Mutational screening of GSD-1a patients identified five novel mutations, viz. Read More

Mol Ther Methods Clin Dev 2019 Jun 10;13:265-273. Epub 2019 Feb 10.

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.

Glycogen storage disease type Ia (GSD Ia) is a rare inherited disease caused by mutations in the glucose-6-phosphatase (G6Pase) catalytic subunit gene (). Absence of G6Pase causes life-threatening hypoglycemia and long-term complications because of the accumulations of metabolic intermediates. Bezafibrate, a pan-peroxisome proliferator-activated receptor (PPAR) agonist, was administered in the context of genome editing with a zinc-finger nuclease-containing vector (AAV-ZFN) and a G6Pase donor vector (AAV-RoG6P). Read More

J Inherit Metab Dis 2019 05 22;42(3):470-479. Epub 2019 Feb 22.

Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Glycogen storage disease type-Ia (GSD-Ia), caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), is characterized by impaired glucose homeostasis with a hallmark hypoglycemia, following a short fast. We have shown that G6pc-deficient (G6pc-/-) mice treated with recombinant adeno-associated virus (rAAV) vectors expressing either wild-type (WT) (rAAV-hG6PC-WT) or codon-optimized (co) (rAAV-co-hG6PC) human (h) G6Pase-α maintain glucose homeostasis if they restore ≥3% of normal hepatic G6Pase-α activity. The co vector, which has a higher potency, is currently being used in a phase I/II clinical trial for human GSD-Ia (NCT03517085). Read More

J Inherit Metab Dis 2019 05 6;42(3):459-469. Epub 2019 Mar 6.

Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

Hepatocellular adenoma/carcinoma (HCA/HCC) is a long-term complication of glycogen storage disease type-Ia (GSD-Ia), which is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in gluconeogenesis. Currently, there is no therapy to address HCA/HCC in GSD-Ia. We have previously shown that a recombinant adeno-associated virus (rAAV) vector-mediated G6PC gene transfer to 2-week-old G6pc-/- mice prevents HCA development. Read More

Hereditas 2018 28;155:32. Epub 2018 Sep 28.

1Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, 410078 Hunan China.

Background: For a proportion of individuals judged clinically to have a recessive Mendelian disease, only one heterozygous pathogenic variant can be found from clinical whole exome sequencing (WES), posing a challenge to genetic diagnosis and genetic counseling. One possible reason is the limited ability to detect disease causal structural variants (SVs) from short reads sequencing technologies. Long reads sequencing can produce longer reads (typically 1000 bp or longer), therefore offering greatly improved ability to detect SVs that may be missed by short-read sequencing. Read More

J Inherit Metab Dis 2018 11;41(6):915

University of Connecticut Health Center, Farmington, Connecticut, USA.

Hum Mol Genet 2019 01;28(1):143-154

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

Glucose-6-phosphatase α (G6Pase) deficiency, also known as von Gierke's Disease or Glycogen storage disease type Ia (GSD Ia), is characterized by decreased ability of the liver to convert glucose-6-phosphate to glucose leading to glycogen accumulation and hepatosteatosis. Long-term complications of GSD Ia include hepatic adenomas and carcinomas, in association with the suppression of autophagy in the liver. The G6pc-/- mouse and canine models for GSD Ia were treated with the pan-peroxisomal proliferator-activated receptor agonist, bezafibrate, to determine the drug's effect on liver metabolism and function. Read More

J Inherit Metab Dis 2018 11 25;41(6):913-914. Epub 2018 Sep 25.

Division of Medical Genetics, Duke University Medical Center, DUMC Box 103856, Durham, NC, 27710, USA.

J Hepatol 2018 Nov 5;69(5):1074-1087. Epub 2018 Sep 5.

Institut National de la Santé et de la Recherche Médicale, U1213, Lyon F-69008, France; Université de Lyon, Lyon F-69008 France; Université Lyon I, Villeurbanne F-69622 France. Electronic address:

Background & Aims: Glycogen storage disease type Ia (GSDIa) is a rare genetic disease associated with glycogen accumulation in hepatocytes and steatosis. With age, most adult patients with GSDIa develop hepatocellular adenomas (HCA), which can progress to hepatocellular carcinomas (HCC). In this study, we characterized metabolic reprogramming and cellular defense alterations during tumorigenesis in the liver of hepatocyte-specific G6pc deficient (L. Read More

Mol Metab 2018 10 1;16:100-115. Epub 2018 Aug 1.

Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, F-69008, France; Université de Lyon, Lyon, F-69008, France; Université Lyon1, Villeurbanne, F-69622, France. Electronic address:

Objective: Ectopic lipid accumulation in the liver and kidneys is a hallmark of metabolic diseases leading to non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Moreover, recent data have highlighted a strong correlation between NAFLD and CKD incidences. In this study, we use two mouse models of hepatic steatosis or CKD, each initiated independently of the other upon the suppression of glucose production specifically in the liver or kidneys, to elucidate the mechanisms underlying the development of CKD in the context of NAFLD-like pathology. Read More

J Inherit Metab Dis 2018 11 24;41(6):965-976. Epub 2018 Jul 24.

Division of Medical Genetics, Duke University Medical Center (DUMC), Box 103856, Durham, NC, 27710, USA.

Background: Glycogen storage disease type Ia (GSD Ia) in dogs closely resembles human GSD Ia. Untreated patients with GSD Ia develop complications associated with glucose-6-phosphatase (G6Pase) deficiency. Survival of human patients on intensive nutritional management has improved; however, long-term complications persist including renal failure, nephrolithiasis, hepatocellular adenomas (HCA), and a high risk for hepatocellular carcinoma (HCC). Read More

J Inherit Metab Dis 2018 11;41(6):901-903

, London, England.

J Inherit Metab Dis 2018 11 25;41(6):977-984. Epub 2018 May 25.

Glycogen Storage Disease Program, Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.

Background: Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy. Read More

J Pediatr Hematol Oncol 2019 05;41(4):e260-e262

Division of Pediatric Hematology/Oncology.

Background: Hemophagocytic lymphohystiocytosis (HLH) is characterized by fever, splenomegaly, pancytopenia, and elevated levels of triglycerides and ferritin. These signs and symptoms are common to other metabolic diseases.

Observation: A 5-month-old female infant, who presented with fever, respiratory distress, massive hepatomegaly, and bicytopenia, was diagnosed as having HLH and chemotherapy was initiated. Read More

J Inherit Metab Dis 2018 May 8. Epub 2018 May 8.

Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 8N240C, NIH, 10 Center Drive, Bethesda, MD, 20892-1830, USA.

Glycogen storage disease type Ia (GSD-Ia) deficient in glucose-6-phosphatase-α (G6Pase-α) is a metabolic disorder characterized by impaired glucose homeostasis and a long-term complication of hepatocellular adenoma/carcinoma (HCA/HCC). Mitochondrial dysfunction has been implicated in GSD-Ia but the underlying mechanism and its contribution to HCA/HCC development remain unclear. We have shown that hepatic G6Pase-α deficiency leads to downregulation of sirtuin 1 (SIRT1) signaling that underlies defective hepatic autophagy in GSD-Ia. Read More

Zhonghua Nei Ke Za Zhi 2018 Apr;57(4):264-269

Department of General Internal Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

To analyze the clinical features of secondary gout in glycogen storage disease type Ⅰa (GSD Ⅰa), so as to improve the awareness of this disease. The clinical features, laboratory findings, treatments and prognosis of 5 GSD Ⅰa patients with secondary gout who had been admitted to the Peking Union Medical College Hospital during 2006 to 2016 were collected and analyzed. GSD Ⅰa was confirmed by liver biopsy and genotyping. Read More

J Inherit Metab Dis 2018 11 29;41(6):929-936. Epub 2018 Mar 29.

Section of Metabolic Diseases, Beatrix Children's Hospital University Medical Center Groningen, University of Groningen, PO Box 30 001, 9700 RB, Groningen, The Netherlands.

Background: The purpose of this project was to develop a telemedicine platform that supports home site monitoring and integrates biochemical, physiological, and dietary parameters for individual patients with hepatic glycogen storage disease (GSD).

Methods And Results: The GSD communication platform (GCP) was designed with input from software developers, GSD patients, researchers, and healthcare providers. In phase 1, prototyping and software design of the GCP has occurred. Read More

Liver Res 2017 Sep;1(3):174-180

Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) that is expressed primarily in the liver, kidney, and intestine. G6Pase-α catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis, and is a key enzyme for endogenous glucose production. The active site of G6Pase-α is inside the endoplasmic reticulum (ER) lumen. Read More

Transplant Proc 2018 Apr 22;50(3):905-909. Epub 2018 Mar 22.

Nephrology Dialysis and Transplant Unit, University of Modena and Reggio Emilia, AOU Policlinico of Modena, Modena, Italy.

Mucormycosis is an uncommonly encountered fungal infection in solid organ transplantation. The infection is severe and often results in a fatal outcome. The most common presentations are rhino-sino-orbital and pulmonary disease. Read More

Biochem Biophys Res Commun 2018 04 14;498(4):925-931. Epub 2018 Mar 14.

Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. Read More

Hepatology 2018 08 27;68(2):780-782. Epub 2018 Apr 27.

Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Probiotics Antimicrob Proteins 2019 03;11(1):143-149

Efficiency, Quality and Costs in Health Services Research Group (EFISALUD), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.

Gut Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal disorders characterised by relapsing and remitting inflammation of the gastrointestinal tract. The two most common types of IBDs are ulcerative colitis and Crohn's disease. Patients with glycogen storage disease (GSD) type Ia present with gastrointestinal symptoms such as recurrent abdominal pain, bloating and changes in stool form or frequency, which is clinically difficult to distinguish from IBD. Read More

J Inherit Metab Dis 2018 11 12;41(6):985-995. Epub 2018 Feb 12.

Department of Translational Medical Science, Section of Pediatrics, Federico II University, Via Sergio Pansini, 5, 80131, Naples, Italy.

Background: Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). GSDIa patients are at higher risk of developing insulin-resistance (IR). Mitochondrial dysfunction has been implicated in the development of IR. Read More

Mol Ther 2018 03 31;26(3):814-821. Epub 2018 Jan 31.

Discovery Research, Alexion Pharmaceuticals, Inc., 75 Sidney Street, Cambridge, MA 02139, USA. Electronic address:

Glycogen storage disease type Ia (GSD1a) is an inherited metabolic disorder caused by the deficiency of glucose-6-phosphatase (G6Pase). GSD1a is associated with life-threatening hypoglycemia and long-term liver and renal complications. We examined the efficacy of mRNA-encoding human G6Pase in a liver-specific G6Pase mouse model (L-G6PC) that exhibits the same hepatic biomarkers associated with GSD1a patients, such as fasting hypoglycemia, and elevated levels of hepatic glucose-6-phosphate (G6P), glycogen, and triglycerides. Read More

J Pediatr Endocrinol Metab 2018 Mar;31(4):473-478

Department of Pediatrics, Naval Medical Center Portsmouth, Portsmouth, VA, USA.

Background: Glycogen storage diseases (GSDs) are a collection of disorders related to glycogen synthesis or degradation that classically present in infancy with hypoglycemia, failure to thrive and hepatomegaly; however, their phenotype can vary significantly.

Case Presentation: We present the cases of two children, 5 years old and 3.5 years old, who were referred to endocrinology for short stature. Read More

J Med Case Rep 2017 Nov 12;11(1):319. Epub 2017 Nov 12.

Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, 1 RWJ Place, MEB 486 PO Box 19, New Brunswick, NJ, 08903, USA.

Background: Glycogen storage disease type Ia is a genetic disorder that is associated with persistent fasting hypoglycemia and the inability to produce endogenous glucose. The development of diabetes with glycogen storage disease is exceedingly rare. The underlying pathogenesis for developing diabetes in these patients is unclear, and there are no guidelines for treatment. Read More

Mol Genet Metab 2017 11 1;122(3):95-98. Epub 2017 Sep 1.

Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA. Electronic address:

GSD Ia (von Gierke Disease, Glycogen Storage Disease Type Ia) is a devastating genetic disorder with long-term sequelae, such as non-alcoholic fatty liver disease and renal failure. Down-regulated autophagy is involved in the development of hepatic metabolic dysfunction in GSD Ia; however, the role of autophagy in the renal pathology is unknown. Here we show that autophagy is impaired and endoplasmic reticulum (ER) stress is increased in the kidneys of a mouse model of GSD Ia. Read More

Hepatology 2017 12 30;66(6):2042-2054. Epub 2017 Oct 30.

Department of Pediatrics, Center for Liver Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

It is a long-standing enigma how glycogen storage disease (GSD) type I patients retain a limited capacity for endogenous glucose production despite the loss of glucose-6-phosphatase activity. Insight into the source of residual endogenous glucose production is of clinical importance given the risk of sudden death in these patients, but so far contradictory mechanisms have been proposed. We investigated glucose-6-phosphatase-independent endogenous glucose production in hepatocytes isolated from a liver-specific GSD Ia mouse model (L-G6pc mice) and performed real-time analysis of hepatic glucose fluxes and glycogen metabolism in L-G6pc mice using state-of-the-art stable isotope methodologies. Read More

BMC Ophthalmol 2017 Jun 28;17(1):107. Epub 2017 Jun 28.

Eye Unit, San Paolo Hospital, University of Milan, Milan, Italy.

Background: We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD).

Case Presentation: A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. Read More

Pediatr Diabetes 2017 08 1;18(5):327-331. Epub 2017 Jun 1.

Glycogen Storage Disease Program, Connecticut Children's Medical Center, Hartford, Connecticut.

Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes. Read More

PLoS Genet 2017 May 30;13(5):e1006819. Epub 2017 May 30.

Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.

A deficiency in glucose-6-phosphatase-α (G6Pase-α) in glycogen storage disease type Ia (GSD-Ia) leads to impaired glucose homeostasis and metabolic manifestations including hepatomegaly caused by increased glycogen and neutral fat accumulation. A recent report showed that G6Pase-α deficiency causes impairment in autophagy, a recycling process important for cellular metabolism. However, the molecular mechanism underlying defective autophagy is unclear. Read More

Clin Chim Acta 2017 Aug 11;471:46-54. Epub 2017 May 11.

Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, India. Electronic address:

The frequency of rs2229611, previously reported in Chinese, Caucasians, Japanese and Hispanics, was investigated for the first time in Indian ethnicity. We analyzed its role in the progression of Glycogen Storage Disease type-Ia (GSD-Ia) and breast cancer. Genotype data on rs2229611 revealed that the risk of GSD-Ia was higher (P=0. Read More

J Inherit Metab Dis 2017 09 10;40(5):695-702. Epub 2017 Apr 10.

Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, PO Box 30 001, Groningen, 9700 RB, The Netherlands.

Objective: To study heterogeneity between patients with glycogen storage disease type Ia (GSD Ia), a rare inherited disorder of carbohydrate metabolism caused by the deficiency of glucose-6-phosphatase (G6Pase).

Study Design: Descriptive retrospective study of longitudinal clinical and biochemical data and long-term complications in 20 GSD Ia patients. We included 11 patients with homozygous G6PC mutations and siblings from four families carrying identical G6PC genotypes. Read More

J Genet 2017 Mar;96(1):19-23

Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz 5166/15731, Iran.

Glycogen storage diseases (GSDs) are caused by abnormalities in enzymes that are involved in the regulation of gluconeogenesis and glycogenolysis. GSD I, an autosomal recessive metabolic disorder, is the most common GSD and has four subtypes. Here, we examined GSD Ia caused by the defective glucose-6-phosphatase catalytic (G6PC) gene. Read More