{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:56:34Z","timestamp":1781744194054,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    GDP\u2010mannose pyrophosphorylase B (GMPPB) deficiency is a congenital disorder of glycosylation due to pathogenic variants of the\n                    <jats:italic>GMPPB<\/jats:italic>\n                    gene. GMPPB catalyzes GDP\u2010mannose synthesis, an early step in multiple glycosylation pathways, including N\u2010glycosylation, O\u2010mannosylation, C\u2010mannosylation, and glycosylphosphatidylinositol\u2010anchor formation. In fibroblasts (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20093), myoblasts (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20094) and in muscle biopsies (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20094) from a total of 7 GMPPB\u2010deficient patients we found evidence of glycogen accumulation, both in cytosol and in lysosome\u2010like vesicles, presence of heterogeneous storage material, and expansion of the lysosomal compartment. Due to the excess of glycogen in cells and tissues, we investigated acid alpha\u2010glucosidase (GAA) in cultured GMPPB fibroblasts. GAA activity was reduced in GMPPB cells, with an impaired protein maturation and lysosomal localization. Incubation of cells with human recombinant GAA (rhGAA), that is fully glycosylated, showed complete correction of GAA activity, normal processing and lysosomal trafficking, with complete clearance of glycogen storage. These results suggest a secondary impairment of specific lysosomal functions in GMPPB deficiency and add information on the complexity of the pathophysiology of this disorder.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70136","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T21:50:31Z","timestamp":1768859431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GMPPB\u2010CDG Results in Lysosomal Dysfunction and Acid Alpha\u2010Glucosidase Deficiency"],"prefix":"10.1002","volume":"49","author":[{"given":"Carla","family":"Damiano","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"},{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Tarallo","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"},{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-652X","authenticated-orcid":false,"given":"Vincenza","family":"Gragnaniello","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Strollo","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Fecarotta","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"},{"name":"European Reference Network for Metabolic Diseases (MetabERN)  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Rosaria","family":"Tuzzi","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Polishchuk","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Montefusco","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Valanzano","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"},{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Assunto","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"},{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Minopoli","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"},{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7528-2415","authenticated-orcid":false,"given":"Roberto Della","family":"Casa","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Polishchuk","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1786-3037","authenticated-orcid":false,"given":"Stijn L. M. in 't","family":"Groen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Erasmus University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Clinical Genetics Erasmus University Medical Center  Rotterdam the Netherlands"},{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Luis","family":"Medina","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4590","authenticated-orcid":false,"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[{"name":"Neuromuscular Disorders Research Unit, Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-4054","authenticated-orcid":false,"given":"Rosalba","family":"Carrozzo","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology and Diagnosis of Mitochondrial Disorders, Laboratory of Medical Genetics, Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Emmerich","sequence":"additional","affiliation":[{"name":"Friedrich\u2010Baur\u2010Institut, Neurologische Klinik, Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-8131","authenticated-orcid":false,"given":"Benedikt","family":"Schoser","sequence":"additional","affiliation":[{"name":"Friedrich\u2010Baur\u2010Institut, Neurologische Klinik, Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7042-2482","authenticated-orcid":false,"given":"W. W. M. Pim","family":"Pijnappel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Erasmus University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Clinical Genetics Erasmus University Medical Center  Rotterdam the Netherlands"},{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Parenti","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"},{"name":"Department of Translational Medical Sciences Federico II University  Naples Italy"},{"name":"European Reference Network for Metabolic Diseases (MetabERN)  Naples Italy"},{"name":"Scuola Superiore Meridionale (SSM, School of Advanced Studies) Genomics and Experimental Medicine Program University of Naples, Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Essentials of Glycobiology [Internet]","author":"Freeze H. 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