Search Our Scientific Publications & Authors

Mol Genet Metab Rep 2022 Jun 11;31:100880. Epub 2022 May 11.

BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.

Background: Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive disorder caused by deficiency of glucose-6-phosphatase (G6Pase), resulting in fasting hypoglycemia. Dietary treatment with provision of uncooked cornstarch (UCCS) or a novel modified cornstarch () is available to treat hypoglycemia, yet choice of carbohydrate to achieve a desirable glycemic control is debated.C-glucose breath test (C-GBT) can be used to examine glucose metabolism from different carbohydrate sources via CO in breath. Read More

Eur J Med Genet 2022 Jun 9;65(6):104518. Epub 2022 May 9.

Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel-Hashomer, Israel. Electronic address:

Avoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e. Read More

Mol Genet Metab Rep 2022 Jun 15;31:100848. Epub 2022 Feb 15.

Department of Pediatrics, Duke University Medical Center, United States of America.

Although inflammatory bowel disease is a well-described feature of glycogen storage disease type Ib, it has been reported in only a small number of individuals with glycogen storage disease type Ia (GSDIa). We describe, to our knowledge, the first patient with GSDIa and very early-onset inflammatory bowel disease (VEO-IBD). Larger studies are needed to better understand this possible association, elucidate the mechanism of VEO-IBD in GSDIa, and inform management. Read More

Arthritis Res Ther 2022 02 26;24(1):58. Epub 2022 Feb 26.

Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China.

Background: This study aimed to explore the clinical features of gout in adult patients with glycogen storage disease type Ia (GSD Ia).

Methods: Ninety-five adult patients with GSD Ia admitted to Peking Union Medical College Hospital were retrospectively analysed. A clinical diagnosis of GSD Ia was confirmed in all patients through gene sequencing. Read More

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

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

Int J Neonatal Screen 2021 Nov 16;7(4). Epub 2021 Nov 16.

Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe 650-0017, Japan.

Glycogen storage disease type Ia (GSDIa) is an autosomal recessive disorder caused by glucose-6-phosphatase (G6PC) deficiency. GSDIa causes not only life-threatening hypoglycemia in infancy, but also hepatocellular adenoma as a long-term complication. Hepatocellular adenoma may undergo malignant transformation to hepatocellular carcinoma. Read More

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

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

Anim Genet 2021 Dec 5;52(6):900-902. Epub 2021 Oct 5.

Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, 3001, Switzerland.

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

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

Quant Imaging Med Surg 2021 Jun;11(6):2785-2791

Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Glycogen storage disease type Ia (GSD Ia) is a rare disease caused by a deficiency of hepatic glucose-6-phosphatase (G6Pase). Here, we report a 17-year-old Chinese boy with GSD Ia. Clinical manifestations of the patient included hepatomegaly, growth retardation, doll face, and biochemical abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia. Read More

BMJ Case Rep 2021 Mar 25;14(3). Epub 2021 Mar 25.

Serviço de Endocrinologia, Centro Hospitalar Universitário Lisboa Norte EPE, Lisboa, Portugal

A 22-year-old woman with type Ia glycogen storage disease was referred to the endocrinology department with new-onset diabetes mellitus-glycated haemoglobin (HbA1c) of 8.2%. She had suffered from repeated bouts of hypoglycaemia since the first days of her life. Read More

J Inherit Metab Dis 2021 07 7;44(4):879-892. Epub 2021 Apr 7.

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

Prevention of hypertriglyceridemia is one of the biomedical targets in Glycogen Storage Disease type Ia (GSD Ia) patients, yet it is unclear how hypoglycemia links to plasma triglyceride (TG) levels. We analyzed whole-body TG metabolism in normoglycemic (fed) and hypoglycemic (fasted) hepatocyte-specific glucose-6-phosphatase deficient (L-G6pc ) mice. De novo fatty acid synthesis contributed substantially to hepatic TG accumulation in normoglycemic L-G6pc mice. Read More

J Med Case Rep 2021 Feb 16;15(1):75. Epub 2021 Feb 16.

Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto Prefecture, 860-8556, Japan.

Background: Glycogen storage disease (GSD) type Ia is a glycogenesis disorder with long-term complications such as hepatomegaly and renal dysfunction and is caused by congenital loss of glucose-6-phosphatase (G6Pase) expression. G6Pase is essential for the final step of gluconeogenesis and glycogenolysis, and its deficiency causes clinical hypoglycemia in the fasting state during infancy. Contrastingly, patients also show blood glucose trends and glucose intolerance similar to those in type II diabetes. Read More

Mol Ther 2021 04 23;29(4):1602-1610. Epub 2020 Dec 23.

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), deficient in glucose-6-phosphatase-α (G6PC), is characterized by impaired glucose homeostasis and a hallmark of fasting hypoglycemia. We have developed a recombinant adeno-associated virus (rAAV) vector-mediated gene therapy for GSD-Ia that is currently in a phase I/II clinical trial. While therapeutic expression of the episomal rAAV-G6PC clinical vector is stable in mice, the long-term durability of expression in humans is currently being established. Read More

Mol Genet Metab Rep 2020 Dec 20;25:100659. Epub 2020 Oct 20.

Post Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

The rs2229611 SNP (:c.*23T>C) in the 3'UTR region of the gene affects the stability of the glucose-6-phosphatase mRNA and occurs in a higher frequency in patients with glycogenosis Ia (GSD Ia) in some populations. Herein, a group of Brazilian patients ( = 116) was analyzed by NGS and the frequency of rs2229611:T>C was determined. Read More

Eur Rev Med Pharmacol Sci 2020 10;24(19):10036-10044

Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: Glycogen storage disease type Ia (GSDIa) is a glucose metabolic disorder. GSDIa patients are characterized by hypoglycemia, hepatomegaly, hyperlipidemia, and hyperlactacidemia. This retrospective study aimed to review the lipid status, explore lipid treatment targets, and assess preferable lipid-lowering drugs. Read More

Medicine (Baltimore) 2020 Oct;99(42):e22644

The Department of Gastroenterology.

Rationale: Glycogen storage disease type IA (GSD IA) is an inherited disorder of glycogen metabolism characterized by fasting hypoglycemia, hyperuricemia, and hyperlipidemia including hypertriglyceridemia (HTG). Patients have a higher risk of developing acute pancreatitis (AP) because of HTG. AP is a potentially life-threatening disease with a wide spectrum severity. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Oct;37(10):1162-1166

Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Objective: To explore the genetic etiology of a patient with glycogen accumulation type Ⅰa with gout as the main clinical feature.

Methods: Clinical data of the patient was collected. The patient and her parents were subjected to next generation sequencing (NGS). Read More

Diabet Med 2021 02 19;38(2):e14373. Epub 2020 Sep 19.

Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Dis Model Mech 2020 09 18;13(9). Epub 2020 Sep 18.

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

Most patients affected by glycogen storage disease type 1a (GSD1a), an inherited metabolic disorder caused by mutations in the enzyme glucose-6-phosphatase-α (G6Pase-α), develop renal and liver complications, including the development of hepatocellular adenoma/carcinoma. The purpose of this study was to identify potential biomarkers of the pathophysiology of the GSD1a-affected liver. To this end, we used the plasma exosomes of a murine model of GSD1a, the LS- mouse, to uncover the modulation in microRNA expression associated with the disease. Read More

J Inherit Metab Dis 2021 01 2;44(1):118-128. Epub 2020 Jul 2.

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 06 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

Pediatr Int 2020 Oct 28;62(10):1145-1150. Epub 2020 Sep 28.

Division of Pediatric Metabolism, Kanuni Sultan Süleyman Training and Research Hospital, University of Health Sciences, İstanbul, Turkey.

Background: Glycogen storage diseases (GSD) are disorders of autosomal recessive carbohydrate metabolism, characterized by glycogen accumulation. The liver and muscle tissue are commonly affected but patients may present with different clinical manifestations. The presence of glycogen can be demonstrated in biopsies and definitive diagnosis can be made by enzymatic or molecular analysis. Read More

Pediatr Int 2020 06 24;62(6):744-745. Epub 2020 Apr 24.

Division of Pediatric Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

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 11 30;72(5):1638-1653. Epub 2020 Oct 30.

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

Background And Aims: Glycogen storage disease (GSD) type 1a is an inborn error of metabolism caused by defective glucose-6-phosphatase catalytic subunit (G6PC) activity. Patients with GSD 1a exhibit severe hepatomegaly due to glycogen and triglyceride (TG) accumulation in the liver. We have shown that the activity of carbohydrate response element binding protein (ChREBP), a key regulator of glycolysis and de novo lipogenesis, is increased in GSD 1a. Read More