{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:08:35Z","timestamp":1785146915444,"version":"3.55.0"},"reference-count":71,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["DPI2016-79874-R"],"award-info":[{"award-number":["DPI2016-79874-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Neuroimaging studies describing brain circuits\u2019 alterations in cobalamin (vitamin B12)-deficient patients are limited and have not been carried out in patients with inborn errors of cobalamin metabolism. The objective of this study was to assess brain functionality and brain circuit alterations in a patient with an ultra-rare inborn error of cobalamin metabolism, methylmalonic aciduria, and homocystinuria due to cobalamin D disease, as compared with his twin sister as a healthy control (HC). We acquired magnetic resonance imaging (including structural, functional, and diffusion images) to calculate brain circuit abnormalities and combined these results with the scores after a comprehensive neuropsychological evaluation. As compared with HC, the patient had severe patterns of damage, such as a 254% increment of ventricular volume, pronounced subcortical and cortical atrophies (mainly at striatum, cingulate cortex, and precuneus), and connectivity alterations at fronto-striato-thalamic circuit, cerebellum, and corpus callosum. In agreement with brain circuit alterations, cognitive deficits existed in attention, executive function, inhibitory control, and mental flexibility. This is the first study that provides the clinical, genetic, neuroanatomical, neuropsychological, and psychosocial characterization of a patient with the cobalamin D disorder, showing functional alterations in central nervous system motor tracts, thalamus, cerebellum, and basal ganglia, that, as far as we know, have not been reported yet in vitamin B12-related disorders.<\/jats:p>","DOI":"10.3390\/jcm9040990","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T13:39:34Z","timestamp":1585834774000},"page":"990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Brain Circuit Alterations and Cognitive Disability in Late-Onset Cobalamin D Disorder"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-537X","authenticated-orcid":false,"given":"Javier","family":"De Las Heras","sequence":"first","affiliation":[{"name":"Division of Pediatric Metabolism, Cruces University Hospital, 48903 Barakaldo, Spain"},{"name":"Inborn Errors of Metabolism Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Department of Pediatrics, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5769-0178","authenticated-orcid":false,"given":"Ibai","family":"Diez","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA"},{"name":"Neurotechnology Laboratory, Tecnalia Health Department, 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6053-6101","authenticated-orcid":false,"given":"Antonio","family":"Jimenez-Marin","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Biomedical Research Doctorate Program, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Osatek, 48011 Vitoria-Gazteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-2760","authenticated-orcid":false,"given":"Daniela","family":"Ramos-Usuga","sequence":"additional","affiliation":[{"name":"Biomedical Research Doctorate Program, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Venecia","family":"Diaz-Fernandez","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Cruces University Hospital, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leire","family":"Torices","sequence":"additional","affiliation":[{"name":"Biomarkers in Cancer Unit, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1875-6645","authenticated-orcid":false,"given":"Caroline E.","family":"Nunes-Xavier","sequence":"additional","affiliation":[{"name":"Biomarkers in Cancer Unit, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0424 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9100-248X","authenticated-orcid":false,"given":"Rafael","family":"Pulido","sequence":"additional","affiliation":[{"name":"Biomarkers in Cancer Unit, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"IKERBASQUE. Basque Foundation for Science, 48013 Bilbao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-8311","authenticated-orcid":false,"given":"Juan Carlos","family":"Arango-Lasprilla","sequence":"additional","affiliation":[{"name":"Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"IKERBASQUE. Basque Foundation for Science, 48013 Bilbao, Spain"},{"name":"Department of Cell Biology and Histology, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9059-8194","authenticated-orcid":false,"given":"Jesus M.","family":"Cortes","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"IKERBASQUE. Basque Foundation for Science, 48013 Bilbao, Spain"},{"name":"Department of Cell Biology and Histology, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/jimd.12012","article-title":"The clinical presentation of cobalamin-related disorders: From acquired deficiencies to inborn errors of absorption and intracellular pathways","volume":"42","author":"Huemer","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s10545-016-9991-4","article-title":"Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency","volume":"40","author":"Huemer","year":"2017","journal-title":"J. Inherit. Metab. 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