{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:39:00Z","timestamp":1787020740423,"version":"build-2736575974"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Krabbe disease or globoid cell leukodystrophy is a severe neurodegenerative disorder caused by a defect in the\n                      <jats:italic>GALC<\/jats:italic>\n                      gene leading to a deficiency of the enzyme \u00df-galactocerebrosidase. The aim of this work was to describe the natural disease course covering the whole spectrum of the disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Natural history data were collected with a standardized questionnaire, supplemented by medical record data. We defined different forms of the disease according to Abdelhalim et al. (2014). Developmental and disease trajectories were described based on the acquisition and loss of milestones as well as the time of first clearly identifiable symptoms and needs such as spasticity, seizures and tube feeding. MRI was assessed using the scoring system by Loes et al. (1999) and in addition a pattern recognition approach, based on Abdelhalim et al. (2014).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-eight patients were identified, from 27 of these patients 40 MRIs were available; 30 (79%) had an infantile onset, showing first symptoms in their first year of life, almost all (27 out of 30) starting in the first six months. A later onset after the first year of life was observed in 8 patients (21%, range 18\u2009months to 60\u2009years). Irritability, abnormalities in movement pattern as well as general developmental regression were the first symptoms in the infantile group; disease course was severe with rapid progression, e.g. loss of visual fixation, need for tube feeding and then an early death. Gait disorders were the first symptoms in all patients of the later onset groups; progression was variable. The different forms of the disease were characterized by different MRI patterns (infantile: diffuse white matter involvement and cerebellar structures specifically affected, later onset: parieto-occipital white matter and splenium affected, adult: motor tracts specifically affected).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first description of the natural history of Krabbe disease in a larger European cohort using developmental, clinical and MRI data. We would like to highlight the very different clinical and MRI characteristics of the later onset forms. These data are important for counselling affected patients and families and may serve as a basis for future treatment trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-020-01489-3","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T05:03:39Z","timestamp":1599714219000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Natural history of Krabbe disease \u2013 a nationwide study in Germany using clinical and MRI data"],"prefix":"10.1186","volume":"15","author":[{"given":"Sarah Isabel","family":"Krieg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4599-1373","authenticated-orcid":false,"given":"Ingeborg","family":"Kr\u00e4geloh-Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Groeschel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Beck-W\u00f6dl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf A.","family":"Husain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Sch\u00f6ls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Kehrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"1489_CR1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.pediatrneurol.2013.10.001","volume":"50","author":"AN Abdelhalim","year":"2014","unstructured":"Abdelhalim AN, Alberico RA, Barczykowski AL, Duffner PK. 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