UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Glucose-6-phosphatase deficiency (glycogen storage disease I, von Gierke disease)

Author
Angela Sun, MD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

Glucose-6-phosphatase deficiency (G6PD, MIM #232200), also known as von Gierke disease, is a glycogen storage disease (GSD). It was the first GSD to have the responsible enzyme defect identified and therefore is designated GSD I (table 1). The defective enzymes involved in GSD I are mainly active in the liver and kidney. Patients present with manifestations related to hypoglycemia around three to four months of age. The diagnosis is confirmed by genetic testing. Treatment is focused on maintenance of physiologic glucose levels.

GSD I is reviewed in detail here. Other GSDs are reviewed separately. (See "Liver glycogen synthase deficiency (glycogen storage disease 0)" and "Lysosomal acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II, acid maltase deficiency)" and "Lysosome-associated membrane protein 2 deficiency (glycogen storage disease IIb, Danon disease)" and "Glycogen debrancher deficiency (glycogen storage disease III)" and "Glycogen branching enzyme deficiency (glycogen storage disease IV, Andersen disease)" and "Myophosphorylase deficiency (glycogen storage disease V, McArdle disease)" and "Liver phosphorylase deficiency (glycogen storage disease VI, Hers disease)" and "Phosphofructokinase deficiency (glycogen storage disease VII, Tarui disease)".)

A broader overview of GSD is also presented separately. (See "Overview of inherited disorders of glucose and glycogen metabolism".)

EPIDEMIOLOGY

The incidence of GSD I is 1/100,000 live births [1]. It is one of the most common types of GSDs.

PATHOGENESIS AND CLASSIFICATION

The hydrolysis and transport of glucose-6-phosphate require a catalytic hydrolase and microsomal transporters for glucose-6-phosphate (G6P), pyrophosphate, and glucose (figure 1). GSD I is caused by defects in the hydrolase (phosphatase) or translocase:

                                

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Dec 06 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Melis D, Fulceri R, Parenti G, et al. Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature. Eur J Pediatr 2005; 164:501.
  2. Gerin I, Veiga-da-Cunha M, Achouri Y, et al. Sequence of a putative glucose 6-phosphate translocase, mutated in glycogen storage disease type Ib. FEBS Lett 1997; 419:235.
  3. Chen SY, Pan CJ, Nandigama K, et al. The glucose-6-phosphate transporter is a phosphate-linked antiporter deficient in glycogen storage disease type Ib and Ic. FASEB J 2008; 22:2206.
  4. Ihara K, Nomura A, Hikino S, et al. Quantitative analysis of glucose-6-phosphate translocase gene expression in various human tissues and haematopoietic progenitor cells. J Inherit Metab Dis 2000; 23:583.
  5. Chen LY, Shieh JJ, Lin B, et al. Impaired glucose homeostasis, neutrophil trafficking and function in mice lacking the glucose-6-phosphate transporter. Hum Mol Genet 2003; 12:2547.
  6. Chopra AR, Louet JF, Saha P, et al. Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease. Science 2008; 322:1395.
  7. Chou JY, Mansfield BC. Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. Hum Mutat 2008; 29:921.
  8. The Human Gene Mutation Database at http://www.hgmd.cf.ac.uk/ac/index.php (Accessed on September 23, 2016).
  9. Lei KJ, Chen YT, Chen H, et al. Genetic basis of glycogen storage disease type 1a: prevalent mutations at the glucose-6-phosphatase locus. Am J Hum Genet 1995; 57:766.
  10. Matern D, Seydewitz HH, Bali D, et al. Glycogen storage disease type I: diagnosis and phenotype/genotype correlation. Eur J Pediatr 2002; 161 Suppl 1:S10.
  11. Akanuma J, Nishigaki T, Fujii K, et al. Glycogen storage disease type Ia: molecular diagnosis of 51 Japanese patients and characterization of splicing mutations by analysis of ectopically transcribed mRNA from lymphoblastoid cells. Am J Med Genet 2000; 91:107.
  12. Ekstein J, Rubin BY, Anderson SL, et al. Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population. Am J Med Genet A 2004; 129A:162.
  13. Veiga-da-Cunha M, Gerin I, Chen YT, et al. The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. Eur J Hum Genet 1999; 7:717.
  14. Kure S, Suzuki Y, Matsubara Y, et al. Molecular analysis of glycogen storage disease type Ib: identification of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11. Biochem Biophys Res Commun 1998; 248:426.
  15. Rake JP, Visser G, Labrune P, et al. Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I). Eur J Pediatr 2002; 161 Suppl 1:S20.
  16. Cassiman D, Libbrecht L, Verslype C, et al. An adult male patient with multiple adenomas and a hepatocellular carcinoma: mild glycogen storage disease type Ia. J Hepatol 2010; 53:213.
  17. Chen YT, Kishnani PS, Koeberl D. Glycogen Storage Diseases. The Online Metabolic and Molecular Bases of Inherited Disease. http://ommbid.mhmedical.com/ommbid-index.aspx (Accessed on October 22, 2014).
  18. Bandsma RH, Prinsen BH, van Der Velden Mde S, et al. Increased de novo lipogenesis and delayed conversion of large VLDL into intermediate density lipoprotein particles contribute to hyperlipidemia in glycogen storage disease type 1a. Pediatr Res 2008; 63:702.
  19. Bernier AV, Correia CE, Haller MJ, et al. Vascular dysfunction in glycogen storage disease type I. J Pediatr 2009; 154:588.
  20. Ubels FL, Rake JP, Slaets JP, et al. Is glycogen storage disease 1a associated with atherosclerosis? Eur J Pediatr 2002; 161 Suppl 1:S62.
  21. Lee PJ, Celermajer DS, Robinson J, et al. Hyperlipidaemia does not impair vascular endothelial function in glycogen storage disease type 1a. Atherosclerosis 1994; 110:95.
  22. Carvalho PM, Silva NJ, Dias PG, et al. Glycogen Storage Disease type 1a - a secondary cause for hyperlipidemia: report of five cases. J Diabetes Metab Disord 2013; 12:25.
  23. Kishnani PS, Austin SL, Abdenur JE, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med 2014; 16:e1.
  24. Visser G, Rake JP, Fernandes J, et al. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European Study on Glycogen Storage Disease type I. J Pediatr 2000; 137:187.
  25. Roe TF, Thomas DW, Gilsanz V, et al. Inflammatory bowel disease in glycogen storage disease type Ib. J Pediatr 1986; 109:55.
  26. Sechi A, Deroma L, Lapolla A, et al. Fertility and pregnancy in women affected by glycogen storage disease type I, results of a multicenter Italian study. J Inherit Metab Dis 2013; 36:83.
  27. Ryan IP, Havel RJ, Laros RK Jr. Three consecutive pregnancies in a patient with glycogen storage disease type IA (von Gierke's disease). Am J Obstet Gynecol 1994; 170:1687.
  28. Melis D, Pivonello R, Parenti G, et al. Increased prevalence of thyroid autoimmunity and hypothyroidism in patients with glycogen storage disease type I. J Pediatr 2007; 150:300.
  29. Banugaria SG, Austin SL, Boney A, et al. Hypovitaminosis D in glycogen storage disease type I. Mol Genet Metab 2010; 99:434.
  30. Chen YT, Coleman RA, Scheinman JI, et al. Renal disease in type I glycogen storage disease. N Engl J Med 1988; 318:7.
  31. Chen YT. Type I glycogen storage disease: kidney involvement, pathogenesis and its treatment. Pediatr Nephrol 1991; 5:71.
  32. Reitsma-Bierens WC. Renal complications in glycogen storage disease type I. Eur J Pediatr 1993; 152 Suppl 1:S60.
  33. Melis D, Parenti G, Della Casa R, et al. Brain damage in glycogen storage disease type I. J Pediatr 2004; 144:637.
  34. Bianchi L. Glycogen storage disease I and hepatocellular tumours. Eur J Pediatr 1993; 152 Suppl 1:S63.
  35. Minarich LA, Kirpich A, Fiske LM, Weinstein DA. Bone mineral density in glycogen storage disease type Ia and Ib. Genet Med 2012.
  36. Fernandes J, Smit GP, Berger R. Outcome of the treatment of glycogen storage disease. Acta Paediatr Jpn 1988; 30:457.
  37. Rake JP, Visser G, Labrune P, et al. Guidelines for management of glycogen storage disease type I - European Study on Glycogen Storage Disease Type I (ESGSD I). Eur J Pediatr 2002; 161 Suppl 1:S112.
  38. Chen YT, Cornblath M, Sidbury JB. Cornstarch therapy in type I glycogen-storage disease. N Engl J Med 1984; 310:171.
  39. Weinstein DA, Wolfsdorf JI. Effect of continuous glucose therapy with uncooked cornstarch on the long-term clinical course of type 1a glycogen storage disease. Eur J Pediatr 2002; 161 Suppl 1:S35.
  40. Chen YT, Bazzarre CH, Lee MM, et al. Type I glycogen storage disease: nine years of management with cornstarch. Eur J Pediatr 1993; 152 Suppl 1:S56.
  41. Correia CE, Bhattacharya K, Lee PJ, et al. Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib. Am J Clin Nutr 2008; 88:1272.
  42. Nuoffer JM, Mullis PE, Wiesmann UN. Treatment with low-dose diazoxide in two growth-retarded prepubertal girls with glycogen storage disease type Ia resulted in catch-up growth. J Inherit Metab Dis 1997; 20:790.
  43. Weinstein DA, Somers MJ, Wolfsdorf JI. Decreased urinary citrate excretion in type 1a glycogen storage disease. J Pediatr 2001; 138:378.
  44. Das AM, Lücke T, Meyer U, et al. Glycogen storage disease type 1: impact of medium-chain triglycerides on metabolic control and growth. Ann Nutr Metab 2010; 56:225.
  45. Nagasaka H, Hirano K, Ohtake A, et al. Improvements of hypertriglyceridemia and hyperlacticemia in Japanese children with glycogen storage disease type Ia by medium-chain triglyceride milk. Eur J Pediatr 2007; 166:1009.
  46. Bandsma RH, Rake JP, Visser G, et al. Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a. J Pediatr 2002; 140:256.
  47. Schroten H, Roesler J, Breidenbach T, et al. Granulocyte and granulocyte-macrophage colony-stimulating factors for treatment of neutropenia in glycogen storage disease type Ib. J Pediatr 1991; 119:748.
  48. Lee PJ. Glycogen storage disease type I: pathophysiology of liver adenomas. Eur J Pediatr 2002; 161 Suppl 1:S46.
  49. Visser G, Rake JP, Labrune P, et al. Consensus guidelines for management of glycogen storage disease type 1b - European Study on Glycogen Storage Disease Type 1. Eur J Pediatr 2002; 161 Suppl 1:S120.
  50. Melis D, Della Casa R, Parini R, et al. Vitamin E supplementation improves neutropenia and reduces the frequency of infections in patients with glycogen storage disease type 1b. Eur J Pediatr 2009; 168:1069.
  51. Davis MK, Rufo PA, Polyak SF, Weinstein DA. Adalimumab for the treatment of Crohn-like colitis and enteritis in glycogen storage disease type Ib. J Inherit Metab Dis 2008; 31 Suppl 3:505.
  52. Melis D, Parenti G, Gatti R, et al. Efficacy of ACE-inhibitor therapy on renal disease in glycogen storage disease type 1: a multicentre retrospective study. Clin Endocrinol (Oxf) 2005; 63:19.
  53. Franco LM, Krishnamurthy V, Bali D, et al. Hepatocellular carcinoma in glycogen storage disease type Ia: a case series. J Inherit Metab Dis 2005; 28:153.
  54. Limmer J, Fleig WE, Leupold D, et al. Hepatocellular carcinoma in type I glycogen storage disease. Hepatology 1988; 8:531.
  55. Maheshwari A, Rankin R, Segev DL, Thuluvath PJ. Outcomes of liver transplantation for glycogen storage disease: a matched-control study and a review of literature. Clin Transplant 2012; 26:432.
  56. Iyer SG, Chen CL, Wang CC, et al. Long-term results of living donor liver transplantation for glycogen storage disorders in children. Liver Transpl 2007; 13:848.
  57. Demirci G, Becker T, Nyibata M, et al. Results of combined and sequential liver-kidney transplantation. Liver Transpl 2003; 9:1067.
  58. Belingheri M, Ghio L, Sala A, et al. Combined liver-kidney transplantation in glycogen storage disease Ia: a case beyond the guidelines. Liver Transpl 2007; 13:762.
  59. Panaro F, Andorno E, Basile G, et al. Simultaneous liver-kidney transplantation for glycogen storage disease type IA (von Gierke's disease). Transplant Proc 2004; 36:1483.
  60. Marega A, Fregonese C, Tulissi P, et al. Preemptive liver-kidney transplantation in von Gierke disease: a case report. Transplant Proc 2011; 43:1196.
  61. Muraca M, Gerunda G, Neri D, et al. Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet 2002; 359:317.
  62. Talente GM, Coleman RA, Alter C, et al. Glycogen storage disease in adults. Ann Intern Med 1994; 120:218.
  63. Furukawa N, Kinugasa A, Inoue F, et al. Type I glycogen storage disease with vasoconstrictive pulmonary hypertension. J Inherit Metab Dis 1990; 13:102.
  64. Humbert M, Labrune P, Simonneau G. Severe pulmonary arterial hypertension in type 1 glycogen storage disease. Eur J Pediatr 2002; 161 Suppl 1:S93.