{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:44Z","timestamp":1787008904048,"version":"build-2736575974"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001721","name":"University of Groningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001721","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by mutations in the G6PC gene, encoding the catalytic subunit of glucose-6-phosphatase. Early symptoms include severe fasting intolerance, failure to thrive and hepatomegaly, biochemically associated with nonketotic hypoglycemia, fasting hyperlactidemia, hyperuricemia and hyperlipidemia. Dietary management is the cornerstone of treatment aiming at maintaining euglycemia, prevention of secondary metabolic perturbations and long-term complications, including liver (hepatocellular adenomas and carcinomas), kidney and bone disease (hypovitaminosis D and osteoporosis). As impaired vitamin A homeostasis also associates with similar symptoms and is coordinated by the liver, we here analysed whether vitamin A metabolism is affected in GSD Ia patients and liver-specific G6pc\u2212\/\u2212 knock-out mice. Serum levels of retinol and retinol binding protein 4 (RBP4) were significantly increased in both GSD Ia patients and L-G6pc\u2212\/\u2212 mice. In contrast, hepatic retinol levels were significantly reduced in L-G6pc\u2212\/\u2212 mice, while hepatic retinyl palmitate (vitamin A storage form) and RBP4 levels were not altered. Transcript and protein analyses indicate an enhanced production of retinol and reduced conversion the retinoic acids (unchanged LRAT, Pnpla2\/ATGL and Pnpla3 up, Cyp26a1 down) in L-G6pc\u2212\/\u2212 mice. Aberrant expression of genes involved in vitamin A metabolism was associated with reduced basal messenger RNA levels of markers of inflammation (Cd68, Tnf\u03b1, Nos2, Il-6) and fibrosis (Col1a1, Acta2, Tgf\u03b2, Timp1) in livers of L-G6pc\u2212\/\u2212 mice. In conclusion, GSD Ia is associated with elevated serum retinol and RBP4 levels, which may contribute to disease symptoms, including osteoporosis and hepatic steatosis.<\/jats:p>","DOI":"10.1093\/hmg\/ddz283","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T07:11:33Z","timestamp":1574752293000},"page":"264-273","source":"Crossref","is-referenced-by-count":13,"title":["Glycogen storage disease type 1a is associated with disturbed vitamin A metabolism and elevated serum retinol levels"],"prefix":"10.1093","volume":"29","author":[{"given":"Ali","family":"Saeed","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University Multan, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne A","family":"Hoogerland","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Wessel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janette","family":"Heegsma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry G J","family":"Derks","sequence":"additional","affiliation":[{"name":"Section of Metabolic Diseases, Beatrix Children's Hospital, Center for Liver Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline","family":"van der Veer","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Mithieux","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1213, Lyon F-69008"},{"name":"Universite de Lyon, Lyon F-69008, France"},{"name":"Universit\u00e9 Lyon 1, Villeurbanne F-69622, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Rajas","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1213, Lyon F-69008"},{"name":"Universite de Lyon, Lyon F-69008, France"},{"name":"Universit\u00e9 Lyon 1, Villeurbanne F-69622, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike H","family":"Oosterveer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaas Nico","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"2020020509430930600_ref1","volume-title":"GeneReviews(\u00ae)","author":"Bali","year":"1993"},{"key":"2020020509430930600_ref2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/8904_2015_488","article-title":"Safety and efficacy of chronic extended release cornstarch therapy for glycogen storage disease type I","volume":"26","author":"Ross","year":"2016","journal-title":"JIMD Rep."},{"key":"2020020509430930600_ref3","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.ymgme.2009.12.012","article-title":"Hypovitaminosis D in glycogen storage disease type I","volume":"99","author":"Banugaria","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"2020020509430930600_ref4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1023\/B:BOLI.0000016632.13234.56","article-title":"Bone mineral density and markers of bone turnover in patients with glycogen storage disease types I, III and IX","volume":"27","author":"Cabrera-Abreu","year":"2004","journal-title":"J. Inherit. Metab. Dis."},{"key":"2020020509430930600_ref5","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.bbalip.2017.01.007","article-title":"The interrelationship between bile acid and vitamin A homeostasis","volume":"1862","author":"Saeed","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"2020020509430930600_ref6","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1080\/10408398.2015.1060940","article-title":"Vitamin A and the epigenome","volume":"57","author":"Bar-El Dadon","year":"2017","journal-title":"Crit. Rev. Food Sci. 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