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Pathway Description
Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease
Homo sapiens
Disease Pathway
Glycogen storage disease type 1A (GSD1A), or von Gierke disease, is caused by a defect in the G6PC gene which codes for Glucose-6-phosphatase. Glucose-6-phosphatase hydrolyzes glucose-6-phosphate to glucose and is responsible for the regulation of blood glucose level. A defect in this enzyme results in accumulation of glycogen in affected tissues, like liver and kidney; decreased glucose level; and accumulation of lactate. Glycogen storage disease type 1A causes clinically significant end-organ disease with significant morbidity. Usually it presents in childhood. Symptoms include seizures, irritability, pallor, hypotonia, tremors, loss of consciousness, apnea and hepatomegaly. There is no cure for glycogen storage disease type 1A. Diet therapy can help to prevent hypoglycemia and reduce the symptoms. Liver transplantation may be indicated in cases of hepatic malignancy.
References
Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease References
[Uniprot: P35575](http://www.uniprot.org/uniprot/P35575)
[eMedicine: Article 1116574-overview](http://emedicine.medscape.com/article/1116574-overview)
[eMedicine: Article 119318-overview](http://emedicine.medscape.com/article/119318-overview)
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.49 Heilbronn: SPS Verlagsgesellschaft
Akanuma J, Nishigaki T, Fujii K, Matsubara Y, Inui K, Takahashi K, Kure S, Suzuki Y, Ohura T, Miyabayashi S, Ogawa E, Iinuma K, Okada S, Narisawa K: 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 Mar 13;91(2):107-12.
Pubmed: 10748407
Bianchi L: Glycogen storage disease I and hepatocellular tumours. Eur J Pediatr. 1993;152 Suppl 1:S63-70.
Pubmed: 8391447
Chevalier-Porst F, Bozon D, Bonardot AM, Bruni N, Mithieux G, Mathieu M, Maire I: Mutation analysis in 24 French patients with glycogen storage disease type 1a. J Med Genet. 1996 May;33(5):358-60.
Pubmed: 8733042
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. doi: 10.1111/jhn.12030. Epub 2013 Jan 7.
Pubmed: 23294025
Salganik SV, Weinstein DA, Shupe TD, Salganik M, Pintilie DG, Petersen BE: A detailed characterization of the adult mouse model of glycogen storage disease Ia. Lab Invest. 2009 Sep;89(9):1032-42. doi: 10.1038/labinvest.2009.64. Epub 2009 Jul 6.
Pubmed: 19581879
Gluconeogenesis References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, Spiegelman BM: Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature. 2003 May 29;423(6939):550-5. doi: 10.1038/nature01667. Epub 2003 May 18.
Pubmed: 12754525
Gray S, Wang B, Orihuela Y, Hong EG, Fisch S, Haldar S, Cline GW, Kim JK, Peroni OD, Kahn BB, Jain MK: Regulation of gluconeogenesis by Kruppel-like factor 15. Cell Metab. 2007 Apr;5(4):305-12. doi: 10.1016/j.cmet.2007.03.002.
Pubmed: 17403374
Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P: Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005 Mar 3;434(7029):113-8. doi: 10.1038/nature03354.
Pubmed: 15744310
Jager S, Handschin C, St-Pierre J, Spiegelman BM: AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12017-22. doi: 10.1073/pnas.0705070104. Epub 2007 Jul 3.
Pubmed: 17609368
Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, Puigserver P: Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J. 2007 Apr 4;26(7):1913-23. doi: 10.1038/sj.emboj.7601633. Epub 2007 Mar 8.
Pubmed: 17347648
Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P: Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett. 2008 Jan 9;582(1):46-53. doi: 10.1016/j.febslet.2007.11.034. Epub 2007 Nov 26.
Pubmed: 18036349
Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM: Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab. 2006 May;3(5):333-41. doi: 10.1016/j.cmet.2006.04.002.
Pubmed: 16679291
Mazzucotelli A, Viguerie N, Tiraby C, Annicotte JS, Mairal A, Klimcakova E, Lepin E, Delmar P, Dejean S, Tavernier G, Lefort C, Hidalgo J, Pineau T, Fajas L, Clement K, Langin D: The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)gamma coactivator-1 alpha and the nuclear receptor PPAR alpha control the expression of glycerol kinase and metabolism genes independently of PPAR gamma activation in human white adipocytes. Diabetes. 2007 Oct;56(10):2467-75. doi: 10.2337/db06-1465. Epub 2007 Jul 23.
Pubmed: 17646210
Kovarova J, Nagar R, Faria J, Ferguson MAJ, Barrett MP, Horn D: Gluconeogenesis using glycerol as a substrate in bloodstream-form Trypanosoma brucei. PLoS Pathog. 2018 Dec 27;14(12):e1007475. doi: 10.1371/journal.ppat.1007475. eCollection 2018 Dec.
Pubmed: 30589893
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