Clin Chim Acta 2017 May 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 Apr 10. 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

Hum Mol Genet 2017 May;26(10):1890-1899

Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). Read More

Sci Rep 2017 Mar 20;7:44408. Epub 2017 Mar 20.

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

Glycogen storage disease type Ia (GSDIa, von Gierke disease) is the most common glycogen storage disorder. It is caused by the deficiency of glucose-6-phosphatase, an enzyme which catalyses the final step of gluconeogenesis and glycogenolysis. Clinically, GSDIa is characterized by fasting hypoglycaemia and hepatic glycogen and triglyceride overaccumulation. Read More

Mol Genet Metab 2017 Mar 10;120(3):229-234. Epub 2017 Jan 10.

Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States. Electronic address:

Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA) and carcinoma (HCC), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). We have previously shown that G6pc-/- mice receiving gene transfer mediated by rAAV-G6PC, a recombinant adeno-associated virus (rAAV) vector expressing G6Pase-α, and expressing 3-63% of normal hepatic G6Pase-α activity maintain glucose homeostasis and do not develop HCA/HCC. However, the threshold of hepatic G6Pase-α activity required to prevent tumor formation remained unknown. Read More

Pediatr Blood Cancer 2016 Dec 30. Epub 2016 Dec 30.

Department of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Turk J Pediatr 2016 ;58(1):12-18

Divisions of Pediatric Gastroenterology and Hepatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Read More

Mol Med Rep 2016 Oct 9;14(4):3251-4. Epub 2016 Aug 9.

Department of Pediatrics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.

Glycogen storage disease type‑Ia (GSD‑Ia) is a rare autosomal recessive disease caused by a mutation in the gene encoding glucose‑6‑phosphate‑α (G6PC). The present study reported the case of a 3‑month‑old female Chinese patient with GSD‑Ia born to consanguineous parents. The aim of the present study was to identify the precise mutation of the G6PC gene associated with this family and to describe the phenotypic characteristics of the patient. Read More

Clin Rheumatol 2016 Nov 2;35(11):2851-2856. Epub 2016 May 2.

Department of General Internal Medicine, Chinese Academy of Sciences and Peking Union Medical College, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Street, Dongcheng District, Beijing, China.

A young female with recurrent tophaceous gout and infertility presented to our clinic. On clinical evaluation, hypoglycaemia, hypertriglyceridaemia, lactic acidosis, and hepatomegaly were noted. Targeted gene sequencing revealed a novel composite heterozygous c. Read More

Mol Genet Metab Rep 2015 Jun 13;3:28-32. Epub 2015 Mar 13.

Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, United States.

Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) activity. In a previous 70-90 week-study, we showed that a recombinant adeno-associated virus (rAAV) vector-mediated gene transfer that restores more than 3% of wild-type hepatic G6Pase-α activity in G6pc (-/-) mice corrects hepatic G6Pase-α deficiency with no evidence of HCA. We now examine the minimal hepatic G6Pase-α activity required to confer therapeutic efficacy. Read More

Liver Transpl 2016 Apr;22(4):516-26

Service de Pathologie, INSERM U1053, Université Bordeaux Segalen, Hôpital Pellegrin, Bordeaux, France.

The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. Read More

Mol Ther 2016 Apr 11;24(4):697-706. Epub 2016 Feb 11.

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

Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P < 0.04). Read More

Orphanet J Rare Dis 2015 Jul 29;10:91. Epub 2015 Jul 29.

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

Background: In GSDIa, glucose 6-phosphate (G6P) accumulates in the endoplasmic reticulum (ER); in GSDIb, G6P levels are reduced in ER. G6P availability directly modulates the activity of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), an ER-bound enzyme playing a key role in the development of the metabolic syndrome (MS).

Objective: To evaluate the prevalence of MS and Insulin Resistance (IR) in GSDIa and GSDIb patients. Read More

JIMD Rep 2015 21;24:123-8. Epub 2015 Jun 21.

Glycogen Storage Disease Program, Division of Pediatric Endocrinology, Department of Pediatrics, University of Florida College of Medicine, 100296, Gainesville, FL, 32610-0296, USA.

Most patients with glycogen storage disease (GSD) type Ib show features related to inflammatory bowel disease (IBD). The development of IBD seems to be associated with the defect of neutrophil function in GSD Ib. Patients with GSD Ia were not recognized to have similar gastrointestinal complaints until recently and are not associated with a neutrophil defect. Read More

Hum Mol Genet 2015 Sep 18;24(18):5115-25. Epub 2015 Jun 18.

Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development and

Glycogen storage disease type-Ia (GSD-Ia) is caused by a lack of glucose-6-phosphatase-α (G6Pase-α or G6PC) activity. We have shown that gene therapy mediated by a recombinant adeno-associated virus (rAAV) vector expressing human G6Pase-α normalizes blood glucose homeostasis in the global G6pc knockout (G6pc(-/-)) mice for 70-90 weeks. The treated G6pc(-/-) mice expressing 3-63% of normal hepatic G6Pase-α activity (AAV mice) produce endogenous hepatic glucose levels 61-68% of wild-type littermates, have a leaner phenotype and exhibit fasting blood insulin levels more typical of young adult mice. Read More

J Inherit Metab Dis 2015 May 30;38(3):537-43. Epub 2015 Jan 30.

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

Hepatic glycogen storage diseases (GSD) underscore the intimate relationship between carbohydrate and lipid metabolism. The hyperlipidemias in hepatic GSD reflect perturbed intracellular metabolism, providing biomarkers in blood to monitor dietary management. In different types of GSD, hyperlipidemias are of a different origin. Read More

Hum Mol Genet 2015 Apr 5;24(8):2287-96. Epub 2015 Jan 5.

Institut National de la Santé et de la Recherche Médicale, U855, Lyon F-69008, France, Université de Lyon, Lyon, F-69008, France, Université Lyon1, Villeurbanne, F-69622, France,

Glycogen storage disease type 1a (GSD1a) is a rare disease due to the deficiency in the glucose-6-phosphatase (G6Pase) catalytic subunit (encoded by G6pc), which is essential for endogenous glucose production. Despite strict diet control to maintain blood glucose, patients with GSD1a develop hepatomegaly, steatosis and then hepatocellular adenomas (HCA), which can undergo malignant transformation. Recently, gene therapy has attracted attention as a potential treatment for GSD1a. Read More

Oncol Lett 2014 Dec 9;8(6):2803-2805. Epub 2014 Oct 9.

Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.

Glycogen storage disease type Ia (GSD-Ia; also termed von Gierke disease) is an inherited metabolic disorder resulting from a glucose-6-phosphatase deficiency. Liver transplantation is considered to be the most effective treatment for GSD-Ia patients. In the present study, the case of a patient with GSD-Ia who received a liver transplantation at 17 years of age is presented. Read More

J Pediatr Gastroenterol Nutr 2017 Feb;64(2):e52-e54

*Division of Pediatric Gastroenterology, Department of Pediatrics †Glycogen Storage Disease Program, Division of Pediatric Endocrinology, Department of Pediatrics, University of Florida College of Medicine, Gainesville ‡Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

J Inherit Metab Dis 2015 May 7;38(3):511-9. Epub 2014 Oct 7.

Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA,

Disorders of the glucose-6-phosphatase (G6Pase)/glucose-6-phosphate transporter (G6PT) complexes consist of three subtypes: glycogen storage disease type Ia (GSD-Ia), deficient in the liver/kidney/intestine-restricted G6Pase-α (or G6PC); GSD-Ib, deficient in a ubiquitously expressed G6PT (or SLC37A4); and G6Pase-β deficiency or severe congenital neutropenia syndrome type 4 (SCN4), deficient in the ubiquitously expressed G6Pase-β (or G6PC3). G6Pase-α and G6Pase-β are glucose-6-phosphate (G6P) hydrolases with active sites lying inside the endoplasmic reticulum (ER) lumen and as such are dependent upon the G6PT to translocate G6P from the cytoplasm into the lumen. The tissue expression profiles of the G6Pase enzymes dictate the disease's phenotype. Read More

Eur J Pediatr 2015 Jan 1;174(1):59-63. Epub 2014 Jul 1.

Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China,

Unlabelled: Glycogen storage disease type Ia (GSDIa) is an autosomal recessively inherited disease characterized by poor tolerance to fasting, growth retardation, and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Germline mutations of glucose-6-phosphatase (G6PC) gene have been identified as a cause of GSDIa. In this study, we performed mutation analysis in five Chinese GSDIa patients belonging to five unrelated families by direct DNA sequencing. Read More

Hepatol Res 2015 Apr 18;45(4):494-9. Epub 2014 Jul 18.

Department of Internal Medicine, Aichi Medical University, Nagakute, Japan.

Glycogen storage disease (GSD) type Ia is caused by a deficiency in glucose-6-phosphatase. Long-term complications, including renal disease, gout, osteoporosis and pulmonary hypertension, develop in patients with GSD type Ia. In the second or third decade, 22-75% of GSD type Ia patients develop hepatocellular adenoma (HCA). Read More

Nihon Shokakibyo Gakkai Zasshi 2014 Apr;111(4):787-96

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University.

A man diagnosed at birth with glycogen storage disease type Ia was found to have multiple hepatocellular adenomas at 15 years of age. At 18 years of age, he underwent transarterial tumor embolization in segments 4 and 5. At 27 years of age, the tumor in segment 4 had increased in size on follow-up computed tomography, and he was referred to our hospital. Read More

Int Braz J Urol 2014 Jan-Feb;40(1):118-22

Division of General Surgery and Department of Surgery, National Taiwan University Hospital, Yuan-Lin Branch, Yuan-Lin, Taiwan, Republic of China.

Main Findings: We reported a case of new-onset, multi-focal hepatic adenoma in an 18 year-old man with no classic risk factors occurring forty months after a renal transplant from a cadaver donor. Histopathology of the adenoma was examined and genotype and phenotype were also analyzed. Histopathologic examination of the adenoma showed no malignancy. Read More

Sultan Qaboos Univ Med J 2014 Feb 27;14(1):e42-9. Epub 2014 Jan 27.

Department of Paediatrics, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.

Objectives: This study aimed to determine the mutation spectrum and prevalence of inborn errors of metabolism (IEM) among Emiratis.

Methods: The reported mutation spectrum included all patients who were diagnosed with IEM (excluding those with lysosomal storage diseases [LSD]) at Tawam Hospital Metabolic Center in Abu Dhabi, United Arab Emirates, between January 1995 and May 2013. Disease prevalence (per 100,000 live births) was estimated from data available for 1995-2011. Read More

Gene 2014 Feb 16;536(2):362-5. Epub 2013 Dec 16.

Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Sino-French Laboratory of Life Science and Genomics, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:

Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive genetic disorder resulting in hypoglycemia, hepatomegaly and growth retardation. It is caused by mutations in the G6PC gene encoding Glucose-6-phosphatase. To date, over 80 mutations have been identified in the G6PC gene. Read More

Transplant Proc 2013 ;45(10):3668-9

General Surgery and Digestive, Hepatobiliopancreatic Surgery, Virgen del Rocio University Hospitals, Seville, Spain. Electronic address:

Von Gierke's disease or glycogen storage disease type Ia (GSD-Ia) is an infrequent metabolic disease caused by an atypical accumulation of glycogen. The principal cause of this pathology is deficiency of the glucose-6-phosphatase enzyme. Herein we have reported a case of a young man with a history of Von Gierke's disease (GSD-Ia) since childhood who developed hepatocellular adenomatosis brought to light by ultrasounds and TACs. Read More

World J Gastroenterol 2013 Nov;19(42):7480-6

Sun Young Ahn, Soo Young Park, Young Oh Kweon, Won Young Tak, Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-721, South Korea.

Hepatocellular adenoma (HCA) is one of the important complications of glycogen storage disease type Ia (GSD-Ia) because it can be transformed into hepatocellular carcinoma. Although surgical resection is a standard treatment of choice for solitary HCA, multiple HCAs in GSD-Ia patients present as therapeutic challenges for curative treatment. Therefore, treatment strategy according to malignant potential is important in management of HCAs in GSD-Ia. Read More

Cardiovasc Intervent Radiol 2014 Aug 23;37(4):1027-33. Epub 2013 Oct 23.

Department of Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria,

Purpose: Both glycogen storage disease type Ia (GSD Ia) and tyrosinemia type I (TYR I) are inherited metabolic disorders that can be complicated by formation of liver adenomas in juvenile/young adult age and/or development of hepatocellular carcinoma. We describe the first application of stereotactic radiofrequency ablation (SRFA) in focal lesions in three patients with inherited metabolic disorders affecting the liver.

Methods: SRFA was applied for removal of single large liver adenomas in a 22-year-old woman and a 20-year-old man with GSD Ia and of a suspicious lesion in a 16-year-old girl with TYR I with α-fetoprotein (AFP) elevation. Read More

Mol Genet Metab 2013 Nov 25;110(3):275-80. Epub 2013 Jun 25.

Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). Read More

J Diabetes Metab Disord 2013 Jun 6;12(1):25. Epub 2013 Jun 6.

Internal Medicine Ward, Coimbra University Hospital, Av, Bissaya Barreto e Praceta Prof, Mota Pinto, 3000-075, Coimbra, Portugal.

Background And Aims: Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder, caused by deficient activity of glucose-6-phosphatase-α. It produces fasting induced hypoglycemia and hepatomegaly, usually manifested in the first semester of life. Besides, it is also associated with growth delay, anemia, platelet dysfunction, osteopenia and sometimes osteoporosis. Read More

Mol Genet Metab 2013 Jun 6;109(2):161-70. Epub 2013 Apr 6.

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

Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (-/-) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Read More

Mol Genet Metab 2013 May 15;109(1):1-2. Epub 2013 Feb 15.

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

JIMD Rep 2013 13;8:25-30. Epub 2012 Jul 13.

Metabolic Unit, Department of Pediatrics, MBBM Foundation, University of Milano Bicocca, San Gerardo Hospital, Via Pergolesi 33, 20900, Monza (MB), Italy,

A 5 years old boy affected with Glycogen Storage Disease type Ia (GSD-Ia) with previous optimal metabolic control developed severe erratic hypoglycemic episodes during continuous nocturnal gastric drip-feeding (CNGDF) administered by nasogastric tube. The episodes of hypoglycemia were not related to pump failure or human errors or wrong position of the tube in the gastrointestinal tract. Hyperinsulinism was also considered in this patient but it was excluded mainly because hypoglycemia was only nocturnal. Read More

IEEE Trans Ultrason Ferroelectr Freq Control 2013 Jan;60(1):88-96

Philips Research North America, Briarcliff Manor, NY, USA.

Ultrasound-mediated delivery (USMD) of novel therapeutic agents in the presence of microbubbles is a potentially safe and effective method for gene therapy offering many desired characteristics, such as low toxicity, potential for repeated treatment, and organ specificity. In this study, we tested the capability of USMD to improve gene expression in mice livers using glycogen storage disease Type Ia as a model disease under systemic administration of naked plasmid DNA. Image-guided therapeutic ultrasound was used in two studies to provide therapeutic ultrasound to mice livers. Read More

Gene 2013 Apr 23;518(2):346-50. Epub 2013 Jan 23.

Gazi University Faculty of Medicine, Department of Pediatric Metabolism and Nutrition, Gazi Hospital, 10th Floor, Beşevler, Ankara, 06540, Turkey.

Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive disorder caused by mutations in the G6PC gene encoding glucose-6-phosphatase (G6Pase), a key enzyme for the maintenance of glucose homeostasis. Molecular analysis is a reliable and accurate way of diagnosing GSD Ia without to need for invasive liver biopsies for enzyme tests. In some ethnic groups and geographic regions, allelic homogeneity was detected in GSD Ia. Read More

J Clin Lipidol 2012 Nov-Dec;6(6):596-600. Epub 2012 Aug 30.

Cardiovascular Research Clinic and Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA 02111, USA.

A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. Read More

Endocrinol Diabetes Metab Case Rep 2013 1;2013:130056. Epub 2013 Dec 1.

Department of Internal Medicine University Hospital Split Split Croatia.

Unlabelled: Glycogen storage disease (GSD) type I is characterized by impaired production of glucose from glycogenolysis and gluconeogenesis resulting in severe hypoglycaemia and increased production of lactic acid, triglyceride and uric acid. The most common type, glycogenosis type Ia, demands a balanced, sufficient carbohydrate intake to preserve normal 24-h glycaemia. Insufficient intake of carbohydrates can cause hypoglycaemia, as the missing glucose-6-phosphatase enzyme cannot free the glucose stored as liver glycogen and nor is gluconeogenesis possible. Read More

Gene 2012 Dec 18;511(1):122-4. Epub 2012 Sep 18.

Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, 230001, Anhui, China.

Mutations in the glucose-6-phosphatase (G6Pase) gene are responsible for glycogen storage disease type Ia (GSD Ia). By genotype analysis of the affected pedigree, we identified a novel type mutation in a Chinese patient with GSD Ia. Mutation analysis was performed for the coding region of G6Pase gene using DNA sequencing and TaqMan gene expression assay was used to further confirm the novel mutation. Read More

J Inherit Metab Dis 2013 Jan 13;36(1):75-81. Epub 2012 Sep 13.

Department of Pediatrics, Takarazuka City Hospital, Takarazuka 665-0827, Japan.

Plasma mannose is suggested to be largely generated from liver glycogen-oriented glucose-6-phosphate. This study examined plasma mannose in glycogen storage disease type Ia (GSD Ia) lacking conversion of glucose-6-phosphate to glucose in the liver. We initially examined fasting--and postprandial 2 h--plasma mannose and other blood carbohydrates and lipids for seven GSD Ia children receiving dietary interventions using cornstarch and six healthy age-matched children. Read More

Gene 2012 Nov 14;509(1):154-7. Epub 2012 Aug 14.

Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.

The manifestations of glycogen storage disease type 1a (GSD 1a) are usually so prominent in childhood that it is readily diagnosed by pediatricians. However, a mild form of the disease may only become apparent during adolescence or adulthood. We observed a brother and sister with subtle manifestations of the disease, which was discovered after the brother's son was diagnosed with typical GSD 1a. Read More

World J Hepatol 2012 Jun;4(6):191-5

Yoshihiro Mikuriya, Akihiko Oshita, Hirotaka Tashiro, Hironobu Amano, Tsuyoshi Kobayashi, Hideki Ohdan, Division of Frontier Medical Science, Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Read More

Hepatology 2012 Nov;56(5):1593-5

Genet Med 2012 Sep 7;14(9):795-9. Epub 2012 Jun 7.

Glycogen Storage Disease Program and Division of Pediatric Endocrinology, Department of Pediatrics, University of Florida, Gainesville, FL, USA.

Purpose: The aim of this study was to characterize the frequency and causes of anemia in glycogen storage disease type I.

Methods: Hematologic data and iron studies were available from 202 subjects (163 with glycogen storage disease Ia and 39 with glycogen storage disease Ib). Anemia was defined as hemoglobin concentrations less than the 5th percentile for age and gender; severe anemia was defined as presence of a hemoglobin <10 g/dl. Read More

Indian Pediatr 2012 Mar;49(3):235-6

Department of Pediatrics and Cardiology, Calcutta National Medical College, Kolkata, India.

A 3 and half years old male child born by consanguineous marriage presented with white forelock and symmetric hypopigmented areas present since birth, similar to his mother and elder sister. Hepatomegaly was noticed at one year of age. Liver biopsy revealed enlarged pale hepatocytes distended with glycogen. Read More

Genet Med 2012 Apr 5. Epub 2012 Apr 5.

Glycogen Storage Disease Program and Division of Pediatric Endocrinology, Department of Pediatrics, University of Florida, Gainesville, Florida, USA.

Purpose:The aim of this study was to characterize the pathogenesis of low bone mineral density in glycogen storage disease type Ia and Ib.Methods:A retrospective chart review performed at the University of Florida Glycogen Storage Disease Program included patients with glycogen storage disease type Ia and Ib for whom dual-energy X-ray absorptiometry analysis was performed. A Z-score less than -2 SD was considered low. Read More

Hepatology 2012 Nov 27;56(5):1719-29. Epub 2012 Aug 27.

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

Unlabelled: Glycogen storage disease type Ia (GSD-Ia), which is characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), is caused by deficiencies in the endoplasmic reticulum (ER)-associated glucose-6-phosphatase-α (G6Pase-α or G6PC) that hydrolyzes glucose-6-phosphate (G6P) to glucose. G6Pase-α activity depends on the G6P transporter (G6PT) that translocates G6P from the cytoplasm into the ER lumen. The functional coupling of G6Pase-α and G6PT maintains interprandial glucose homeostasis. Read More

J Inherit Metab Dis 2012 Jul 7;35(4):671-8. Epub 2012 Feb 7.

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

The emergence of life threatening long-term complications in glycogen storage disease type Ia (GSD-Ia) has emphasized the need for new therapies, such as gene therapy, which could achieve biochemical correction of glucose-6-phosphatase deficiency and reverse clinical involvement. We have developed gene therapy with a novel adeno-associated virus (AAV) vector that: 1) prevented mortality and corrected glycogen storage in the liver, 2) corrected hypoglycemia during fasting, and 3) achieved efficacy with a low number of vector particles in G6Pase-deficient mice and dogs. However, the gradual loss of transgene expression from episomal AAV vector genomes eventually necessitated the administration of a different pseudotype of the AAV vector to sustain dogs with GSD-Ia. Read More

Hum Gene Ther 2012 Apr 8;23(4):407-18. Epub 2012 Mar 8.

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

Glycogen storage disease type Ia (GSD-Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), primarily found in liver and kidney, which causes life-threatening hypoglycemia. Dogs with GSD-Ia were treated with double-stranded adeno-associated virus (AAV) vectors encoding human G6Pase. Administration of an AAV9 pseudotyped (AAV2/9) vector to seven consecutive GSD-Ia neonates prevented hypoglycemia during fasting for up to 8 hr; however, efficacy eventually waned between 2 and 30 months of age, and readministration of a new pseudotype was eventually required to maintain control of hypoglycemia. Read More