{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:01:58Z","timestamp":1791237718293,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100024091","name":"Orchard Therapeutics","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100024091","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>A systematic literature review was conducted to evaluate the emerging evidence on newborn screening (NBS) for metachromatic leukodystrophy (MLD; MIM #250100). The review focuses on (1) screening assay performance, (2) diagnostic confirmation methods and care pathways, (3) feasibility of population-based identification, and (4) the impact of early diagnosis and treatment on health outcomes. Electronic databases were searched in February 2025, and supplementary searches were performed up to 17 June 2025, for articles referencing NBS for MLD and treatments for MLD; 52 publications were eligible for inclusion. Nationwide NBS for MLD is currently carried out in Norway and large prospective pilots are running in Germany, Austria, Italy and the US. MLD meets established Wilson and Jungner criteria, with a reliable screening algorithm, established confirmatory diagnostics, and actionable care pathways. There is ongoing work to develop tools to predict disease severity and subtype. Early intervention\u2014via gene therapy for early-onset MLD and hematopoietic stem cell transplantation (HSCT) for late-onset forms\u2014significantly improves outcomes when initiated before symptom onset. This review provides the first comprehensive synthesis of the evidence supporting MLD for inclusion in NBS programs, underscoring the public health value of early identification and intervention.<\/jats:p>","DOI":"10.3390\/ijns11040103","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T16:09:47Z","timestamp":1762358987000},"page":"103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Newborn Screening for Metachromatic Leukodystrophy: A Systematic Literature Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2506-1961","authenticated-orcid":false,"given":"Lucia","family":"Laugwitz","sequence":"first","affiliation":[{"name":"Neuropaediatrics, General Paediatrics, Diabetology, Endocrinology and Social Paediatrics, University Hospital T\u00fcbingen, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Shenker","sequence":"additional","affiliation":[{"name":"Independent Clinical Consultant, Pennington, NJ 08534, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica F.","family":"Sluys","sequence":"additional","affiliation":[{"name":"And You SARL, 1260 Nyon, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-8104","authenticated-orcid":false,"given":"St\u00e9phane","family":"Pintat","sequence":"additional","affiliation":[{"name":"Oxford PharmaGenesis, Oxford OX13 5QJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6383-9338","authenticated-orcid":false,"given":"David","family":"Whiteman","sequence":"additional","affiliation":[{"name":"Independent Clinical Consultant, Cape Elizabeth, ME 04107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Chanson","sequence":"additional","affiliation":[{"name":"Orchard Therapeutics, London W6 8PW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. 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