{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:13:00Z","timestamp":1792062780172,"version":"4.4.0"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.<\/jats:p>","DOI":"10.3390\/jcm9082326","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T07:31:28Z","timestamp":1595403088000},"page":"2326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases"],"prefix":"10.3390","volume":"9","author":[{"given":"Julia","family":"Hinkel","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wurm","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center\u2014University of Freiburg, 79106 Freiburg, Germany"},{"name":"Department of Pediatrics, St. Hedwigs Campus, University Children\u2019s Hospital Regensburg, 93049 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Rosenbaum-Fabian","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Otfried","family":"Schwab","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald W.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic,  Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Spiekerkoetter","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey N.","family":"Fedosov","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0911-5758","authenticated-orcid":false,"given":"Luciana","family":"Hannibal","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-0468","authenticated-orcid":false,"given":"Sarah C.","family":"Gr\u00fcnert","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,22]]},"reference":[{"key":"ref_1","first-page":"45","article-title":"Glycogen storage diseases: Diagnosis, treatment and outcome","volume":"1","author":"Chen","year":"2016","journal-title":"Transl. 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