{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:03:55Z","timestamp":1789567435803,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Child Neurology Society"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The current clinical nomenclature for individuals with\n                      <jats:italic>ABCD1<\/jats:italic>\n                      gene dysfunction is often uninformative. The disorder was initially described as a combination of adrenal insufficiency and leukodystrophy, leading to the widespread use of \u201cX\u2010linked adrenoleukodystrophy\u201d (ALD). However, this term is inaccurate for individuals who never develop these features.\n                      <jats:italic>ABCD1<\/jats:italic>\n                      dysfunction can cause various symptom complexes: adrenal insufficiency, myelopathy, neuropathy, and leukodystrophy, which may occur consecutively, simultaneously, or not at all.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed an intuitive annotation system to precisely convey phenotype status for individuals with\n                      <jats:italic>ABCD1<\/jats:italic>\n                      dysfunction. The \u201cAMNL score\u201d assesses the presence and severity of [A]drenal insufficiency, [M]yelopathy, [N]europathy, and [L]eukodystrophy, with scores ranging from 0 (no symptoms) to 3 (severe) per domain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Applied to initial clinical encounters with 101 Dutch patients and 30 patients from the California newborn screening (NBS) program, the system identified 33 unique presentations. The most common was isolated mild myelopathy (A0M1N0L0). Including predominantly asymptomatic NBS newborns (mostly A0M0NUL0) broadened the spectrum and highlighted the need for precise classification across ages. Longitudinal use over 2 years in 99 Dutch patients showed progression in one or more domains in 41.4%, most often worsening myelopathy. In the NBS cohort (median follow\u2010up: 3.5 years; range: 0.3\u201312.2), most patients showed no myelopathy or leukodystrophy, though adrenal involvement was detected in half. Initial inter\u2010rater reliability was high (\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \u2009=\u20090.996).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>The AMNL score's ability to quantify domain\u2010specific changes over time makes it valuable for monitoring disease evolution in clinical practice and research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns3.70084","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:28:07Z","timestamp":1785907687000},"page":"219-226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Clinical Progression in X\u2010Linked Adrenoleukodystrophy: The AMNL Scoring System"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-5292","authenticated-orcid":false,"given":"Eda G.","family":"Kabak","sequence":"first","affiliation":[{"name":"Departments of Neurology and Pediatric Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Center, Amsterdam Neuroscience University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilie","family":"Videbaek","sequence":"additional","affiliation":[{"name":"Department of Neurology Stanford University School of Medicine Palo Alto California USA"},{"name":"Department of Pediatrics and Clinical Genetics Centre for Inherited Metabolic Diseases, Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije M. C.","family":"Voermans","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatric Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Center, Amsterdam Neuroscience University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn M. van","family":"Geel","sequence":"additional","affiliation":[{"name":"Noordwest Ziekenhuisgroep Alkmaar the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0233-9361","authenticated-orcid":false,"given":"Keith van","family":"Haren","sequence":"additional","affiliation":[{"name":"Department of Neurology Stanford University School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kemp","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, Amsterdam Gastroenterology Endocrinology Metabolism University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diederik van de","family":"Beek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam University Medical Center, University of Amsterdam Amsterdam Neuroscience Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Engelen","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatric Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Center, Amsterdam Neuroscience University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"298","article-title":"ber diffuse Hirnsclerose","volume":"22","author":"Heubner O. \u00dc.","year":"1897","journal-title":"Charit\u00e9 Ann"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1983.04050080074015"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02901445"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02895263"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01813381"},{"key":"e_1_2_12_7_1","volume-title":"Handbook of Clinical Neurology","author":"Aminoff M. J.","year":"1968"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/85.3.553"},{"issue":"3","key":"e_1_2_12_9_1","first-page":"481","article-title":"Adreno\u2010Leukodystrophy (Sex\u2010Linked Schilder's Disease): A Pathogenetic Hypothesis Based on Ultrastructural Lesions in Adrenal Cortex, Peripheral Nerve and Testis","volume":"76","author":"Powers J. M.","year":"1974","journal-title":"American Journal of Pathology"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1975.00490510033001"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1976.tb04461.x-i1"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00312873"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/361726a0"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.90"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01307"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy299"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001074"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt361"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1008-6"},{"key":"e_1_2_12_20_1","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Scriver C.","year":"2001"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy299"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201374"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-014-0486-0"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201374"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00786"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-51"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(20010201)49:2<186::AID-ANA38>3.0.CO;2-R"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050490"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00313395"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.27.12.1114"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009626"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2025.109265"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100380200090"},{"issue":"1","key":"e_1_2_12_34_1","first-page":"66","article-title":"The Genotype and Phenotype Studies of 40 Chinese Patients With X\u2010Linked Adrenoleukodystrophy (X\u2010ALD)","volume":"38","author":"Ping L. L.","year":"2006","journal-title":"Beijing da xue xue bao Yi xue ban= Journal of Peking University Health Sciences"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000110321"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980413)76:5<424::AID-AJMG11>3.0.CO;2-O"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1444"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-015-9672-2"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-024-00605-9"}],"container-title":["Annals of the Child Neurology Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns3.70084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns3.70084","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns3.70084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:10:04Z","timestamp":1789564204000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns3.70084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cns3.70084"],"URL":"https:\/\/doi.org\/10.1002\/cns3.70084","archive":["Portico"],"relation":{},"ISSN":["2831-3267","2831-3267"],"issn-type":[{"value":"2831-3267","type":"print"},{"value":"2831-3267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"assertion":[{"value":"2026-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}