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Despite early dietary intervention, patients remain at risk for long\u2010term neurological impairments, including cognitive deficits, motor speech disorders, and psychiatric conditions. The mechanisms driving these persistent abnormalities remain unclear. This study investigated brain metabolic and structural alterations in adults with classic galactosemia using advanced multiparametric MRI. Six patients (3 males, 3 females; mean age 34.0\u2009\u00b1\u20097.3\u2009years) adhering to lifelong galactose\u2010restricted diets and six age\u2010 and sex\u2010matched controls underwent 3T and 7T MRI, including T1\u2010weighted imaging, pseudo\u2010continuous arterial spin labeling, and high\u2010resolution MR spectroscopic imaging. Patients exhibited significantly lower myo\u2010inositol (mIns) concentrations in cerebellum (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007), putamen (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.023), and cerebral white matter (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001), reflecting a chronic mIns deficiency despite dietary management. Structural analyses revealed reduced volumes of white matter (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), bilateral putamen (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.038), and left thalamus (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.044); alongside increased cortical thickness and reduced cortical surface area, indicating abnormal cortical maturation, particularly in regions associated with motor and cognitive processing. Additionally, cerebral blood flow was elevated in emotion\u2010processing regions, including bilateral amygdala (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.022) and thalamus (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.038). These preliminary findings highlight persistent neurological alterations in classic galactosemia despite dietary management and suggest that chronic mIns deficiency may contribute to the pathophysiology. They underscore the need for larger, longitudinal studies to confirm these results, investigate potential correlations with clinical severity and biochemical markers, and explore therapeutic strategies aimed at modulating mIns metabolism.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70097","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:50:48Z","timestamp":1760417448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Myo\u2010Inositol Deficiency, Structural Brain Changes, and Cerebral Perfusion Alterations in Classic Galactosemia: Preliminary Insights From a Multiparametric\n                    <scp>MRI<\/scp>\n                    Study"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9956-1470","authenticated-orcid":false,"given":"Eva","family":"Niess","sequence":"first","affiliation":[{"name":"High Field MR Center, Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1235-7595","authenticated-orcid":false,"given":"Fabian","family":"Niess","sequence":"additional","affiliation":[{"name":"High Field MR Center, Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0130-3463","authenticated-orcid":false,"given":"Wolfgang","family":"Bogner","sequence":"additional","affiliation":[{"name":"High Field MR Center, Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"},{"name":"Christian Doppler Laboratory for MR Imaging Biomarkers (BIOMAK), Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Svatkova","sequence":"additional","affiliation":[{"name":"Danish Research Centre for Magnetic Resonance, Department of Radiology and Nuclear Medicine Copenhagen University Hospital \u2013 Amager and Hvidovre  Copenhagen Denmark"},{"name":"Department of Radiology and Nuclear Medicine Copenhagen University Hospital \u2013 Amager and Hvidovre  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0702-4374","authenticated-orcid":false,"given":"Marion","family":"Herle","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Allergology and Endocrinology, Austrian Newborn Screening, Department of Paediatrics and Adolescent Medicine Medical University of Vienna  Vienna 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