Type 1 glycogen storage disease - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

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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Etiology

Pathophysiology

Images

Simplified scheme of glycogen synthesis and degradation in the liver. Key to scheme: UDP-glucose, uridine diphosphoglucose; 1. hexokinase/glucokinase; 2. glucose 6-phosphatase; 3. phosphoglucomutase; 4. glycogen synthase; 5. branching enzyme; 6. glycogen phosphorylase; 7. debranching enzyme; 8. phosphofructokinase; 9. fructose 1,6-bisphosphatase; 10. acid maltase; 11. pyruvate dehydrogenase

Citations

Key Articles

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]

Other Online Resources

GeneTests
PreventionGenetics
Metabolic Emergency Protocol: emergency letter generator

Referenced Articles

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]
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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]
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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]
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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]
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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]
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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]
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