{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:29:40Z","timestamp":1791901780847,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>MRPS<\/jats:italic>\n                    genes, which encode components of the small mitoribosomal subunit, have not been previously linked to adult\u2010onset neurological diseases. These genes play a critical role in mitochondrial translation and the biogenesis of the oxidative phosphorylation system. Whole Genome Sequencing was performed on adult patients presenting with an unexplained neurological picture. In parallel, functional studies were carried out in patient\u2010derived fibroblasts to assess mitochondrial translation and the status of oxidative phosphorylation pathways. Bi\u2010allelic pathogenic variants in\n                    <jats:italic>MRPS22<\/jats:italic>\n                    ,\n                    <jats:italic>MRPS23<\/jats:italic>\n                    , and\n                    <jats:italic>MRPS34<\/jats:italic>\n                    were identified in four patients from unrelated families. All patients presented a similar complex neurological phenotype, including cerebellar ataxia, distal motor neuropathy, pyramidal syndrome, and a distinctive leukoencephalopathy on brain MRI. Additional findings included elevated cerebrospinal fluid (CSF) protein levels and profound cerebral folate deficiency. Functional analyses revealed impaired mitochondrial translation and multiple defects in oxidative phosphorylation. Treatment with oral folinic acid resulted in clinical stabilization, radiological improvement, and normalization of CSF 5\u2010methyltetrahydrofolate levels. Our findings expand the spectrum of mitochondrial diseases caused by defects in mitoribosomal proteins, highlighting their role in adult\u2010onset neurological disorders with distinctive brain imaging features, high CSF protein levels, and cerebral folate deficiency.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70139","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:55:07Z","timestamp":1767920107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>MRPS<\/scp>\n                    Genes Causing Leukoencephalopathy With Profound Cerebral Folate Deficiency in Adults"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4069-0483","authenticated-orcid":false,"given":"Daniele","family":"Mandia","sequence":"first","affiliation":[{"name":"Neurology Department AP\u2010HP, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Reference Center for Metabolic and Lysosomal Neurological Diseases  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metodi D.","family":"Metodiev","sequence":"additional","affiliation":[{"name":"Imagine Institute, Laboratory for Genetics of Mitochondrial Disorders Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Benoist","sequence":"additional","affiliation":[{"name":"Service de Biochimie m\u00e9tabolique, H\u00f4pital Universitaire Necker Enfants Malades, AP\u2010HP, Facult\u00e9 de Pharmacie Universit\u00e9 Paris Saclay  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Gaignard","sequence":"additional","affiliation":[{"name":"Service de Biochimie, Centre de r\u00e9f\u00e9rence Des Maladies Mitochondriales, FILNEMUS, CHU Bic\u00eatre Universit\u00e9 Paris\u2010Saclay  Le Kremlin Bicetre France"},{"name":"Laboratoire Multi\u2010Site SeqOIA\u2010FMG 2025  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Ruzzenente","sequence":"additional","affiliation":[{"name":"Imagine Institute, Laboratory for Genetics of Mitochondrial Disorders Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Zuchner","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Hussmann Institute for Human Genomics University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danique","family":"Beijer","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Hussmann Institute for Human Genomics University of Miami Miller School of Medicine  Miami Florida USA"},{"name":"Division of Translational Genomics of Neurodegenerative Diseases, Hertie\u2010Institute for Clinical Brain Research University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorka","family":"Fernandez\u2010Eulate","sequence":"additional","affiliation":[{"name":"AP\u2010HP, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Reference Center for Muscle Diseases Nord\u2010Paris\u2010Est, Myology Institute  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"R\u00f6tig","sequence":"additional","affiliation":[{"name":"Imagine Institute, Laboratory for Genetics of Mitochondrial Disorders Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5104-2935","authenticated-orcid":false,"given":"Foudil","family":"Lamari","sequence":"additional","affiliation":[{"name":"Metabolic Biochemistry Unit, Department of Biochemistry of Neurometabolic Diseases Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Rucheton","sequence":"additional","affiliation":[{"name":"Metabolic Biochemistry Unit, Department of Biochemistry of Neurometabolic Diseases Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Rouzier","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics National Center for Mitochondrial Diseases, Nice Teaching Hospital  Nice France"},{"name":"Department of Medical Genetics Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile Riera","family":"Navarro","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics National Center for Mitochondrial Diseases, Nice Teaching Hospital  Nice France"},{"name":"Department of Medical Genetics Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira Ait\u2010El\u2010Mkadem","family":"Saadi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics National Center for Mitochondrial Diseases, Nice Teaching Hospital  Nice France"},{"name":"Department of Medical Genetics Universit\u00e9 C\u00f4te d'Azur, CNRS, INSERM, IRCAN  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Cintas","sequence":"additional","affiliation":[{"name":"Service de Neurologie, Centre de r\u00e9f\u00e9rence Des Maladies Neuromusculaires Toulouse University Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-9435","authenticated-orcid":false,"given":"Julien","family":"Maquet","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Reference Center for Inborn Errors of Metabolism, G2M Network 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