{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:09:15Z","timestamp":1792728555965,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK107900"],"award-info":[{"award-number":["DK107900"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Long\u2010term complications are common among patients with classic galactosemia (CG) and show both reduced penetrance and variable expressivity. Overall prevalence rates for complications in cognitive, motor, and speech\/voice\/language outcomes among US and European cohorts are known. However, age at presentation, whether these complications cluster, and what factors might associate with penetrance remain unknown. These gaps in knowledge limit prognostic accuracy for young patients and leave open the question of whether complications in different outcome domains may have shared modifiers. Here we addressed these questions using data from medical records and family survey responses from 164 patients and 77 controls. We found that for cases who experienced long\u2010term complications, the median age at presentation of challenges in cognitive outcome was about 5\u2009years, in motor outcome was about 3\u2009years, and in speech\/voice\/language outcome was about 2\u2009years. We also found highly significant clustering of complications in these three domains. Finally, we tested six factors for possible association with penetrance: history of severe neonatal symptoms,\n                    <jats:italic>GALT<\/jats:italic>\n                    genotype and predicted residual GALT activity, days of neonatal milk exposure, rigor of non\u2010dairy galactose restriction in early childhood, peak red blood cell (RBC) galactose\u20101P level in infancy, and baseline RBC galactose\u20101P level in early childhood. Of these, only history of severe neonatal brain\u2010related symptoms consistently associated with higher penetrance, and only detectable predicted residual GALT activity consistently associated with lower penetrance. Combined, these results substantially extend what is known about the natural history of long\u2010term complications in CG.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70020","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T10:20:26Z","timestamp":1743762026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Patterns of Penetrance and Expressivity of Long\u2010Term Outcomes in Classic Galactosemia"],"prefix":"10.1002","volume":"48","author":[{"given":"Nicole H.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia S.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Hendrickson","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared J.","family":"Druss","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7947-5807","authenticated-orcid":false,"given":"Judith L.","family":"Fridovich\u2010Keil","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"GeneReviews","author":"Berry G.","year":"2020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R300025200"},{"key":"e_1_2_10_4_1","first-page":"79","article-title":"Newborn Screening for Galactosemia in the United States: Looking Back, Looking Around, and Looking Ahead","volume":"15","author":"Pyhtila B. M.","year":"2015","journal-title":"JIMD Reports"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9990-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01800204"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02072514"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1047-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2023.107708"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9221-4"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12786"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1355962"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9372-y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2022.07.005"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2000.109148"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02143794"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa006"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-018-0136-9"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12556"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1374"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9575-x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009583200"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.398"},{"key":"e_1_2_10_24_1","volume-title":"Vineland Adaptive Behavior Scales, Third Edition (Vineland\u20103)","author":"Sparrow S.","year":"2016"},{"key":"e_1_2_10_25_1","volume-title":"Book RStudio: Integrated Development Environment for R","author":"Team P","year":"2023"},{"key":"e_1_2_10_26_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"Team RC","year":"2023"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.52402"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-006-0255-4"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200003000-00005"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.11.052"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0067-x"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T04:18:32Z","timestamp":1761106712000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,2]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/jimd.70020"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70020","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,2]]},"assertion":[{"value":"2024-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70020"}}