eprintid: 1545364 rev_number: 42 eprint_status: archive userid: 608 dir: disk0/01/54/53/64 datestamp: 2017-03-18 20:41:37 lastmod: 2021-09-22 22:22:29 status_changed: 2017-06-23 13:32:43 type: article metadata_visibility: show creators_name: Lakshmanan, R creators_name: Adams, ME creators_name: Lynch, DS creators_name: Kinsella, JA creators_name: Phadke, R creators_name: Schott, JM creators_name: Murphy, E creators_name: Rohrer, JD creators_name: Chataway, J creators_name: Houlden, H creators_name: Fox, NC creators_name: Davagnanam, I title: Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F85 divisions: F86 note: Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: OBJECTIVE: To provide an overview of the phenotype of 2 clinically, radiologically, and pathologically similar leukodystrophies, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and alanyl-transfer RNA synthetase 2 mutation-related leukodystrophy (AARS2-L), and highlight key differentiating features. METHODS: ALSP and AARS2-L cases were identified from the adult-onset leukodystrophy database at our institution. In addition, cases with imaging findings were identified from a literature review. The phenotypic features were determined by combining published cases with those from our database. RESULTS: A combined total of 74 cases of ALSP and 10 cases of AARS2-L with neuroimaging data were identified. The mean age at onset was 42 years in ALSP and 26 years in AARS2-L. Cognitive and motor symptoms were the most common symptoms overall in both. Ovarian failure was exclusive to AARS2-L, present in all known female cases. Both ALSP and AARS2-L showed a confluent, asymmetric, predominantly frontoparietal, periventricular pattern of white matter disease with subcortical U-fiber sparing; pyramidal tract and corpus callosum involvement; and diffusion changes in the white matter which we have termed "deep white matter diffusion dots." Central atrophy and corpus callosal thinning were prominent in ALSP and disproportionately mild in AARS2-L when present. ALSP also occasionally showed ventricular abnormalities and calcifications in the frontal periventricular white matter, features not seen in AARS2-L. AARS2-L demonstrates white matter rarefaction which suppresses on fluid-attenuated inversion recovery MRI sequences, a feature not seen in ALSP. CONCLUSIONS: ALSP and AARS2-L share similar clinical, imaging, and pathologic characteristics with key differentiating features that we have highlighted. date: 2017-04 date_type: published official_url: http://doi.org/10.1212/NXG.0000000000000135 oa_status: green full_text_type: pub pmcid: PMC5312114 language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1211990 doi: 10.1212/NXG.0000000000000135 pii: NG2016003467 lyricists_name: Chataway, Jeremy lyricists_name: Davagnanam, Indran lyricists_name: Fox, Nicholas lyricists_name: Houlden, Henry lyricists_name: Lynch, David lyricists_name: Phadke, Rahul lyricists_name: Rohrer, Jonathan lyricists_name: Schott, Jonathan lyricists_id: JCHAT72 lyricists_id: IDAVA10 lyricists_id: NCIFO25 lyricists_id: HJHOU44 lyricists_id: DLYNC04 lyricists_id: RPHAD38 lyricists_id: JDROH34 lyricists_id: JMSCH12 actors_name: Chataway, Jeremy actors_name: Laslett, David actors_id: JCHAT72 actors_id: DLASL34 actors_role: owner actors_role: impersonator full_text_status: public publication: Neurology Genetics volume: 3 number: 2 article_number: e135 event_location: United States issn: 2376-7839 citation: Lakshmanan, R; Adams, ME; Lynch, DS; Kinsella, JA; Phadke, R; Schott, JM; Murphy, E; ... Davagnanam, I; + view all <#> Lakshmanan, R; Adams, ME; Lynch, DS; Kinsella, JA; Phadke, R; Schott, JM; Murphy, E; Rohrer, JD; Chataway, J; Houlden, H; Fox, NC; Davagnanam, I; - view fewer <#> (2017) Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy. Neurology Genetics , 3 (2) , Article e135. 10.1212/NXG.0000000000000135 <https://doi.org/10.1212/NXG.0000000000000135>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1545364/1/Chataway_Neurol%20Genet-2017-Lakshmanan-.pdf