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Here, we review the literature and present new data from a sixth patient carrying the uncharacterized variant c.133A&gt;G; p.Thr45Ala in the <jats:italic>SLC35A1<\/jats:italic> gene. In addition to known clinical symptoms of SLC35A1\u2010CDG, the patient presents with failure to thrive, short stature, caf\u00e9\u2010au\u2010lait spot, and preauricular ear tag. Even though examination of CDG markers transferrin (Tf), alpha\u20101\u2010antitrypsin (A1AT), and apolipoprotein CIII (ApoCIII) revealed no abnormalities in serum, the patient\u2019s fibroblasts showed significant alterations of protein expression or glycosylation of ICAM1, GP130, and TGN46 as well as differences in staining signals of lectins MAL\u2010I, RCAI, and SNA and deviations in LC\u2010MS analysis of total cellular N\u2010glycans. Transfection of CRISPR\/Cas9 generated <jats:italic>SLC35A1<\/jats:italic> HEK293 knockout cells with either wild\u2010type <jats:italic>SLC35A1<\/jats:italic> or the c.133A&gt;G variant restored the cellular CMP\u2010Neu5Ac to wild\u2010type levels, making a direct effect of p.Thr45Ala on the function of the transporter unlikely. Instead, our results imply that the residual transporter activity of 65% is caused by a decreased stability of the mutated SLC35A1 protein. Since O\u2010GlcNAcylation was affected as well, energy and lipid homeostasis were analyzed and found to be significantly altered. Notably, proliferation and glycosylation of the SLC35A1\u2010deficient patient fibroblasts were enhanced by supplementation of the cell culture medium with 10\u2009mM GlcNAc.<\/jats:p>","DOI":"10.1155\/humu\/6290620","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T12:49:32Z","timestamp":1750942172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Missense Variant in Ultrarare SLC35A1\u2010CDG Alters Cellular Glycosylation, Lipid, and Energy Metabolism Without Affecting CDG Serum Markers"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1488-8079","authenticated-orcid":false,"given":"Kristina","family":"Falkenstein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3353-9197","authenticated-orcid":false,"given":"Lukas","family":"Hoeren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4561-2782","authenticated-orcid":false,"given":"Frauke","family":"Kikul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5344-0865","authenticated-orcid":false,"given":"Gernot","family":"Poschet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-6046","authenticated-orcid":false,"given":"Christian","family":"L\u00fcchtenborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-3300","authenticated-orcid":false,"given":"Ines B.","family":"Brecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Falb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darja","family":"Gauck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-4836","authenticated-orcid":false,"given":"Tobias","family":"Haack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9701-7586","authenticated-orcid":false,"given":"Andreas","family":"Hecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1895-625X","authenticated-orcid":false,"given":"Nastassja","family":"Himmelreich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-1054","authenticated-orcid":false,"given":"J\u00fcrgen G.","family":"Okun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3477-8270","authenticated-orcid":false,"given":"Britta","family":"Br\u00fcgger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-8747","authenticated-orcid":false,"given":"Christian","family":"Thiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"e_1_2_14_1_2","volume-title":"Essentials of Glycobiology [Internet]","author":"Lewis A. 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