{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T19:07:42Z","timestamp":1754161662750,"version":"3.41.2"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100030692","name":"Intramural Research Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100028802","name":"Society of Transnational Academic Researchers Scholars Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100028802","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Lysosomal free sialic acid storage disorder (FSASD) is a rare, multisystem neurodegenerative disease caused by biallelic pathogenic variants in <jats:italic>SLC17A5<\/jats:italic>, encoding sialin. FSASD is characterized by aberrant accumulation of unconjugated \u201cfree\u201d sialic acid (Neu5Ac) within lysosomes. Depending on the specific genetic variants, affected individuals may present with either a rapidly fatal disease or progressive neurodegeneration. While skin fibroblasts have traditionally been used for diagnosis and research, the use of leukocytes in FSASD remains underexplored. This study examined Neu5Ac levels in leukocytes from three individuals with FSASD carrying distinct <jats:italic>SLC17A5<\/jats:italic> variants. The levels in affected individuals were compared to three different groups: (1) the unaffected biological parents of each case; (2) subjects for whom 14 distinct lysosomal storage disorders (LSDs) were excluded based on enzyme analysis (<jats:italic>n<\/jats:italic>\u2009=\u200911); and (3) participants with a confirmed LSD diagnosis, as determined by enzyme analysis (<jats:italic>n<\/jats:italic>\u2009=\u20099). Individuals with FSASD exhibited significantly higher levels of free Neu5Ac compared to their unaffected biological parents (36\u2010fold), LSD\u2010negative subjects (22\u2010fold), and individuals with other LSDs (49\u2010fold). Although total Neu5Ac levels showed a non\u2010significant trend toward an increase in FSASD (1.3\u2010fold), this was primarily due to elevated free Neu5Ac, as bound Neu5Ac was slightly decreased in the leukocytes of FSASD cases relative to their unaffected parents. Overall, these findings highlight leukocytes as a valuable, minimally invasive cellular model for FSASD, offering an alternative, reliable diagnostic tool and a potential platform for monitoring therapeutic responses in future intervention trials.<\/jats:p>","DOI":"10.1002\/jmd2.70029","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T03:00:05Z","timestamp":1750129205000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Utility of Leukocyte Sialic Acid Measurements in Lysosomal Free Sialic Acid Storage Disorder"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6333-4049","authenticated-orcid":false,"given":"Marya S.","family":"Sabir","sequence":"first","affiliation":[{"name":"NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"},{"name":"NIH Oxford\u2010Cambridge Scholars Program University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Pollard","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynne","family":"Wolfe","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Adams","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"},{"name":"Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Ciccone","sequence":"additional","affiliation":[{"name":"Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petcharat","family":"Leoyklang","sequence":"additional","affiliation":[{"name":"Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjan","family":"Huizing","sequence":"additional","affiliation":[{"name":"Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"},{"name":"Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-6959","authenticated-orcid":false,"given":"May Christine V.","family":"Malicdan","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"},{"name":"Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/70585"},{"volume-title":"GeneReviews((R))","year":"1993","author":"Adams D.","key":"e_1_2_12_3_1"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2680621"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.130716"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600464"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.313056"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/303077"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.05.022"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.135896"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010588115479"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527319666200213115747"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/302411"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122373"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(95)06243-2"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2180625"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3961501"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112338"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.03.001"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01957729"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00283373"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.accb.2018.09.001"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01126-7"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10060207"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T05:26:18Z","timestamp":1753766778000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.70029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,16]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/jmd2.70029"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.70029","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"type":"print","value":"2192-8312"},{"type":"electronic","value":"2192-8312"}],"subject":[],"published":{"date-parts":[[2025,6,16]]},"assertion":[{"value":"2025-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70029"}}