{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:02:01Z","timestamp":1791237721973,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["U54NS115052"],"award-info":[{"award-number":["U54NS115052"]}],"id":[{"id":"10.13039\/100006108","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":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neurodegeneration in metachromatic leukodystrophy (MLD) may be preceded by systemic complications. Characterization of these features is critical to define barriers to early diagnosis and treatment eligibility for gene therapy. We utilized medical billing (claims) datasets and a natural history study to capture pre\u2010diagnosis MLD\u2010related events. MLD\u2010related events (ICD\u201010\u2010CM codes) were aggregated into system\u2010based diagnosis clusters, and time to MLD diagnosis (TTD) computed for each organ\u2010system diagnosis cluster. Differences in TTD distribution, instantaneous diagnosis hazard, and survival to MLD diagnosis were compared by sex and payor type. TTD and regression from onset of first symptoms were described using median and inter\u2010quartile range. The claims dataset identified 174 MLD cases (diagnosis \u2264\u20096\u2009years old) with 14 diagnosed within the first year of life. General neurologic concerns (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009138; median 257\u2009days pre\u2010diagnosis), gastrointestinal (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009137; 231\u2009days), seizures (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200948; 236\u2009days), ophthalmologic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200946; 362\u2009days), and language\u2010related events (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200941; 267\u2009days) were common. Time to MLD diagnosis from onset of prodromal clusters was longer for children with non\u2010commercial insurance: most prominent with seizures (survival logrank\n                    <jats:italic>p<\/jats:italic>\n                    value &lt;\u20090.02) and non\u2010degenerative neurological symptoms (survival logrank\n                    <jats:italic>p<\/jats:italic>\n                    value\u2009&lt;\u20090.04). Similar findings were noted in our analysis of a second claims dataset. The natural history cohort demonstrated a similar pattern of prodromal disease features and delayed diagnosis. This study defines barriers to MLD diagnosis and highlights prodromal periods of pre\u2010regression symptomatology, further supporting the need for early screening in this fatal disorder of childhood.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70049","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:44:24Z","timestamp":1748911464000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterizing Diagnostic Delays in Metachromatic Leukodystrophy: A Real\u2010World Data Approach"],"prefix":"10.1002","volume":"48","author":[{"given":"Ali","family":"Mohajer","sequence":"first","affiliation":[{"name":"Qral Group  New Jersey New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-2501","authenticated-orcid":false,"given":"Anjana","family":"Sevagamoorthy","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Bean","sequence":"additional","affiliation":[{"name":"Orchard Therapeutics  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Mutua","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Pang","sequence":"additional","affiliation":[{"name":"Orchard Therapeutics  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Ann","family":"Adang","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Neurology, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61641"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2022.09.009"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab304"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12388"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-020-01734-1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.193"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2024.03.487"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.155"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.01.010"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2014.93"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0313-y"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073815595078"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.2067"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40348-020-00103-7"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233158"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30374-9"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2010.03821.x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.08.002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/15513815.2019.1588442"},{"key":"e_1_2_11_21_1","article-title":"An Unusual Presentation of Gall Bladder Papillomatosis in Association With Metachromatic Leukodystrophy","volume":"2018","author":"Kurian J. J.","year":"2018","journal-title":"BML Case Reports"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/15513815.2018.1424277"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.08.006"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2016.08.081"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002811"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2022.01.020"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00451.x"},{"key":"e_1_2_11_28_1","first-page":"286","article-title":"Late Infantile Form Metachromatic Leukodystrophy: Report of One Case","volume":"33","author":"Shian W. J.","year":"1992","journal-title":"Zhonghua Minguo Guo Xiao Er Ke Yi Xue Hui Za Zhi"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108453"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2013.12.016"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-01017-5"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b05274"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/CPJ.0000000000000783"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-14-199"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5216"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1220-4"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011047"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2024.03.003"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-020-00621-6"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jdn.10306"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01058.x"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22919"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1113-6"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2020.106448"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0560-1"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02017-1"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.11752"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.33710"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2023-064088"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-024-03044-w"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02518-z"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12298"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70049","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70049","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:06:45Z","timestamp":1784678805000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/jimd.70049"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70049","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"assertion":[{"value":"2024-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70049"}}