Search Our Scientific Publications & Authors

Orphanet J Rare Dis 2021 Jun 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 Mar 19. Epub 2021 Mar 19.

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 Feb 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.

J Inherit Metab Dis 2021 Jan 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

Orphanet J Rare Dis 2020 02 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 03;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 01 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 03 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