Highlights & Basics
- Type I glycogen storage disease is a disorder of glucose-6-phosphate breakdown, associated with impaired glycogenolysis and gluconeogenesis. It typically presents in infancy with hypoglycemia, hyperlacticacidemia, hypertriglyceridemia, and hepatomegaly.
- Provision of a continuous glucose source is the mainstay of treatment, often in the form of frequent feeding with uncooked cornstarch.
- Long-term sequelae include hepatic adenomas, hepatocellular carcinoma, and nephropathy.
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Definition
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Citations
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 Nov;16(11):e1.[Abstract][Full Text]
1. 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 Nov;16(11):e1.[Abstract][Full Text]
2. Xu N, Han X, Zhang Y, et al. Clinical features of gout in adult patients with type Ia glycogen storage disease: a single-centre retrospective study and a review of literature. Arthritis Res Ther. 2022 Feb 26;24(1):58.[Abstract][Full Text]
3. Ai J, He W, Huang X, et al. A case report of acute pancreatitis with glycogen storage disease type IA in an adult patient and review of the literature. Medicine (Baltimore). 2020 Oct 16;99(42):e22644.[Abstract][Full Text]
4. Chou JY, Jun HS, Mansfield BC. Glycogen storage disease type 1 and G6Pase-beta deficiency: etiology and therapy. Nat Rev Endocrinol. 2010 Dec;6(12):676-88.[Abstract][Full Text]
5. 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 Aug 30;129A(2):162-4.[Abstract]
6. Seydewitz HH, Matern D. Molecular genetic analysis of 40 patients with glycogen storage disease type Ia: 100% mutation detection rate and 5 novel mutations. Hum Mutat. 2000 Jan;15(1):115-6.[Abstract][Full Text]
7. Kim YM, Choi JH, Lee BH, et al. Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia. Orphanet J Rare Dis. 2020 Feb 11;15(1):45.[Abstract][Full Text]
8. 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 Oct;57(4):766-71.[Abstract][Full Text]
9. Chou JY, Matern D, Mansfield BC, et al. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex. Curr Mol Med. 2002 Mar;2(2):121-43.[Abstract]
10. Beyzaei Z, Geramizadeh B. Molecular diagnosis of glycogen storage disease type I: a review. EXCLI J. 2019 Jan 30:18:30-46.[Abstract][Full Text]
11. 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 Oct:161 Suppl 1:S112-9.[Abstract]
12. Wolfsdorf JI, Crigler JF. Effect of continuous glucose therapy begun in infancy on the long-term clinical course of patients with type I glycogen storage disease. J Pediatr Gastroenterol Nutr. 1999 Aug;29(2):136-43.[Abstract][Full Text]
13. Wolfsdorf JI, Keller RJ, Landy H, et al. Glucose therapy for glycogenosis type 1 in infants: comparison of intermittent uncooked cornstarch and continuous overnight glucose feedings. J Pediatr. 1990 Sep;117(3):384-91.[Abstract]
14. Wolfsdorf, JI, Ehrlich S, Landy HS, et al. Optimal daytime feeding regimen to prevent postprandial hypoglycemia in type 1 glycogen storage disease. Am J Clin Nutr. 1992 Sep;56(3):587-92. [Abstract]
15. Shah KK, O'Dell SD. Effect of dietary interventions in the maintenance of normoglycaemia in glycogen storage disease type 1a: a systematic review and meta-analysis. J Hum Nutr Diet. 2013 Aug;26(4):329-39.[Abstract]
16. Hayde M, Widhalm K. Effects of cornstarch treatment in very young children with type I glycogen storage disease. Eur J Pediatr. 1990 Jun;149(9):630-3.[Abstract]
17. Derks TG, Martens DH, Sentner CP, et al. Dietary treatment of glycogen storage disease type Ia: uncooked cornstarch and/or continuous nocturnal gastric drip-feeding? Mol Genet Metab. 2013 May;109(1):1-2.[Abstract]
18. 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;88:1272-1276.[Abstract][Full Text]
19. Bandsma RH, Smit GP, Kuipers F. Disrupted lipid metabolism in glycogen storage disease type 1. Eur J Pediatr. 2002;161:S65-S69.[Abstract]
20. Moosburner S, Wiering L, Gül-Klein S, et al. Over 30 years of pediatric liver transplantation at the Charité-Universitätsmedizin Berlin. J Clin Med. 2022 Feb 9;11(4):900.[Abstract][Full Text]
21. Davis MK, Weinstein DA. Liver transplantation in children with glycogen storage disease: controversies and evaluation of the risk/benefit of this procedure. Pediatr Transplant. 2008;12:137-145.[Abstract]
22. 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;13:848-852.[Abstract][Full Text]
23. Melis D, Minopoli G, Balivo F, et al. Vitamin E improves clinical outcome of patients affected by glycogen storage disease type Ib. JIMD Rep. 2016;25:39-45.[Abstract][Full Text]
24. Ghosh A, Allamarvdasht M, Pan CJ, et al. Long-term correction of murine glycogen storage disease type Ia by recombinant adeno-associated virus-1-mediated gene transfer. Gene Ther. 2006;13:321-329.[Abstract]
25. Weinstein DA, Correia CE, Conlon T, et al. Adeno-associated virus-mediated correction of a canine model of glycogen storage disease type 1a. Hum Gene Ther. 2010;21:903-910.[Abstract]
26. ClinicalTrials.gov. A study of adeno-associated virus serotype 8-mediated gene transfer of glucose-6-phosphatase in patients with glycogen storage disease type Ia (GSDIa). ClinicalTrials.gov ID: NCT05139316. Dec 2023 [internet publication].[Full Text]
27. ClinicalTrials.gov. A study of mRNA-3745 in adult and pediatric participants with glycogen storage disease type 1a (GSD1a). ClinicalTrials.gov ID: NCT05095727. Oct 2023 [internet publication].[Full Text]
28. Veiga-da-Cunha M, Chevalier N, Stephenne X, et al. Failure to eliminate a phosphorylated glucose analog leads to neutropenia in patients with G6PT and G6PC3 deficiency. Proc Natl Acad Sci U S A. 2019 Jan 22;116(4):1241-50.[Abstract][Full Text]
29. Grünert SC, Derks TGJ, Adrian K, et al. Efficacy and safety of empagliflozin in glycogen storage disease type Ib: data from an international questionnaire. Genet Med. 2022 Aug;24(8):1781-8.[Abstract][Full Text]
30. Wortmann SB, Van Hove JLK, Derks TGJ, et al. Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor. Blood. 2020 Aug 27;136(9):1033-43.[Abstract][Full Text]
31. Weinstein DA, Wolfsdorf JI. Effect of continuous glucose therapy with uncooked cornstarch on the long-term clinical course of type Ia glycogen storage disease. Eur J Pediatr. 2002;161:S35-S39.[Abstract]
32. Wang DQ, Fiske LM, Carreras CT, et al. Natural history of hepatocellular adenoma formation in glycogen storage disease type I. J Pediatr. 2011 Sep;159(3):442-6.[Abstract][Full Text]
33. Haring MPD, Peeks F, Oosterveer MH, et al. High childhood serum triglyceride concentrations associate with hepatocellular adenoma development in patients with glycogen storage disease type Ia. JHEP Rep. 2022 Aug;4(8):100512.[Abstract][Full Text]
34. Dambska M, Labrador EB, Kuo CL, et al. Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control. Pediatr Diabetes. 2017 Aug;18(5):327-31.[Abstract]
35. Kaiser N, Gautschi M, Bosanska L, et al. Glycemic control and complications in glycogen storage disease type I: results from the Swiss registry. Mol Genet Metab. 2019 Apr;126(4):355-61.[Abstract]
36. Chen YT, Coleman RA, Scheinman JI, et al. Renal disease in type 1 glycogen storage disease. N Engl J Med. 1988;318:7-11.[Abstract]
37. Weinstein DA, Somers MJG, Wolfsdorf JI. Decreased urinary citrate excretion in type 1a glycogen storage disease. J Pediatr. 2001 Mar;138(3):378-82.[Abstract]
38. Wolfsdorf JI, Laffel LMB, Crigler JF. Metabolic control and renal dysfunction in type I glycogen storage disease. J Inherit Metab Dis. 1997;20:559-568.[Abstract]
39. Martens DH, Rake JP, Navis G, et al. Renal function in glycogen storage disease type I, natural course, and renopreservative effects of ACE inhibition. Clin J Am Soc Nephrol. 2009;4:1741-1746.[Abstract]
40. Franco LM, Krishnamurthy V, Bali D, et al. Hepatocellular carcinoma in glycogen storage disease type Ia: a case series. J Inherit Metab Dis. 2005;28:153-162.[Abstract]
41. Labrune P, Trioche P, Duvaltier I, et al. Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature. J Pediatr Gastroenterol Nutr. 1997;243:276-279.[Abstract]
42. Weinstein DA, Roy CN, Fleming MD, et al. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood. 2002;100:3776-3781.[Abstract][Full Text]
43. Schwahn B, Rauch F, Wendel U, et al. Low bone mass in glycogen storage disease type 1 is associated with reduced muscle force and poor metabolic control. J Pediatr. 2002;141:350-356.[Abstract]
44. Martens DH, Rake JP, Schwarz M, et al. Pregnancies in glycogen storage disease type Ia. Am J Obstet Gynecol. 2008 Jun;198(6):646.e1-7.[Abstract][Full Text]
45. Grünert SC, Rosenbaum-Fabian S, Schumann A, et al. Two successful pregnancies and first use of empagliflozin during pregnancy in glycogen storage disease type Ib. JIMD Rep. 2022 May 18;63(4):303-8.[Abstract][Full Text]
46. Calderwood S, Kilpatrick L, Douglas SD, et al. Recombinant human granulocyte colony-stimulating factor therapy for patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease type 1b. Blood. 2001;97:376-382.[Abstract]
47. Melis D, Pivonello R, Parenti G, et al. Increased prevalence of thyroid autoimmunity and hypothyroidism in patients with glycogen storage disease type 1. J Pediatr. 2007;150:300-305.[Abstract]
48. Bernier AV, Correia CE, Haller MJ, et al. Vascular dysfunction in glycogen storage disease type I. J Pediatr. 2009;154:588-591.[Abstract]
49. Peeks F, Hoogeveen IJ, Feldbrugge RL, et al. A retrospective in-depth analysis of continuous glucose monitoring datasets for patients with hepatic glycogen storage disease: recommended outcome parameters for glucose management. J Inherit Metab Dis. 2021 Sep;44(5):1136-50.[Abstract][Full Text]
50. Rossi A, Venema A, Haarsma P, et al. A prospective study on continuous glucose monitoring in glycogen storage disease type Ia: toward glycemic targets. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3612-23.[Abstract][Full Text]
51. Restaino I, Kaplan BS, Stanley C, et al. Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease. J Pediatr. 1993;122:392-396.[Abstract]
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