{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:55:29Z","timestamp":1792461329287,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["Telethon Grant 2003\u20102005\/Clinical research project B \"Clinical trial in Metachromatic Leukodystrophy\" Communicating Editor: Carla E. Hollak"],"award-info":[{"award-number":["Telethon Grant 2003\u20102005\/Clinical research project B \"Clinical trial in Metachromatic Leukodystrophy\" Communicating Editor: Carla E. Hollak"]}],"id":[{"id":"10.13039\/501100002426","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":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this study, we characterize the natural course of metachromatic leukodystrophy (MLD), explore intra\/inter group differences, and identify biomarkers to monitor disease progression. This is a longitudinal observational study. Genotype and characteristics at disease onset were recorded. Time\u2010to\u2010event analyses were performed to assess time to major disease\u2010related milestones in different subgroups. Longitudinal trajectories of nerve conduction velocities (NCV), brain MRI score, and brainstem auditory evoked responses (BAERs) were described. We recruited 22 late\u2010infantile, 14 early\u2010juvenile, 5 late\u2010juvenile, and 4 adult MLD patients. Thirty\u2010four were prospectively evaluated (median FU time 43\u2009months). In late\u2010infantile patients, the attainment of independent walking was associated with a later age at dysphagia. In early\u2010juvenile, the presence of isolated cognitive impairment at onset was not a favorable prognostic factor. Late\u2010infantile and early\u2010juvenile subjects showed similar rapid loss of ambulation and onset of seizures, but late\u2010infantile displayed earlier loss of trunk control, dysphagia, and death. We found significant differences in all major disease\u2010related milestones (except death) between early\u2010juvenile and late\u2010juvenile patients. Late\u2010juvenile and adult patients both presented with a predominant cognitive impairment, mild\/no peripheral neuropathy, lower brain MRI score at plateau compared to LI\/EJ, and later cerebellar involvement. NCV and BAER were consistently severely abnormal in late\u2010infantile but not in older subjects, in whom both NCV and BAER were variably affected, with no deterioration over time in some cases. This study clarifies intra\/inter group differences between MLD subtypes and provides additional indications regarding reliable clinical and instrumental tools to monitor disease progression and to serve as areference to evaluate the efficacy of future therapeutic interventions inthe different MLD variants.<\/jats:p>","DOI":"10.1002\/jimd.12388","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T21:10:25Z","timestamp":1618521025000},"page":"1151-1164","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Metachromatic leukodystrophy: A single\u2010center longitudinal study of 45 patients"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7476-4087","authenticated-orcid":false,"given":"Francesca","family":"Fumagalli","sequence":"first","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR\u2010TIGET) IRCCS San Raffaele Scientific Institute  Milan Italy"},{"name":"Pediatric Immunohematology Unit and BMT Program IRCCS San Raffaele Scientific Institute  Milan Italy"},{"name":"Department of Neurology IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto A.","family":"Zambon","sequence":"additional","affiliation":[{"name":"Department of Neurology IRCCS San Raffaele Scientific Institute  Milan Italy"},{"name":"Vita\u2010Salute San Raffaele University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola M. V.","family":"Rancoita","sequence":"additional","affiliation":[{"name":"University Centre of Statistics in the Biomedical Sciences Vita\u2010Salute San Raffaele University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Baldoli","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Canale","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR\u2010TIGET) IRCCS San Raffaele Scientific Institute  Milan Italy"},{"name":"Department of Specialistic Neurological Rehabilitation IRCCS Multimedica  Sesto San Giovanni Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Spiga","sequence":"additional","affiliation":[{"name":"Clinical Molecular Biology Laboratory IRCCS San Raffaele Scientific Institute  Milan 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Raffaele Scientific Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sarzana","sequence":"additional","affiliation":[{"name":"Pediatric Immunohematology Unit and BMT Program IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lorioli","sequence":"additional","affiliation":[{"name":"Pediatric Immunohematology Unit and BMT Program IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Cesani","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR\u2010TIGET) IRCCS San Raffaele Scientific Institute  Milan Italy"},{"name":"AGC Biologics S.p.a  Bresso (MI) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Natali Sora","sequence":"additional","affiliation":[{"name":"Department of 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