{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:31:44Z","timestamp":1790011904987,"version":"4.0.1"},"reference-count":8,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,30]],"date-time":"2018-01-30T00:00:00Z","timestamp":1517270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Catholic University of Sacred Heart (UCSC)"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Juvenile\u2010 or adult\u2010onset forms of severe 5,10\u2010methylenetetrahydrofolate reductase (<jats:styled-content style=\"fixed-case\">MTHFR<\/jats:styled-content>) deficiency manifesting as complicated hereditary spastic paraplegia have rarely been described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two siblings with mental retardation developed a progressive spastic paraparesis in their late teens. Their diagnostic assessment included extensive neurophysiologic, neuroimaging and metabolic studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Brain magnetic resonance imaging showed occipital white matter alterations, and electromyography documented a mixed polyneuropathy. Severe hyperhomocisteinemia (&gt;150\u00a0\u03bcmol\/L) associated with the characteristic amino acid profile suggested a diagnosis of severe <jats:styled-content style=\"fixed-case\">MTHFR<\/jats:styled-content> deficiency, confirmed by <jats:italic><jats:styled-content style=\"fixed-case\">MTHFR<\/jats:styled-content><\/jats:italic> direct sequencing. Treatment with betaine and vitamins benefitted patients' symptoms and diagnostic features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Severe <jats:styled-content style=\"fixed-case\">MTHFR<\/jats:styled-content> deficiency can be a rare, treatable cause of autosomal recessive complicated hereditary spastic paraplegia. Its screening should be part of the diagnostic flowchart for these disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13557","type":"journal-article","created":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:18:44Z","timestamp":1514506724000},"page":"602-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Severe 5,10\u2010methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia"],"prefix":"10.1111","volume":"25","author":[{"given":"A.","family":"Perna","sequence":"first","affiliation":[{"name":"Institute of Neurology Catholic University of Sacred Heart (UCSC) Fondazione Policlinico Gemelli Rome"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Masciullo","sequence":"additional","affiliation":[{"name":"IRCSS Santa Lucia Rome"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Modoni","sequence":"additional","affiliation":[{"name":"Institute of Neurology Catholic University of Sacred Heart (UCSC) Fondazione Policlinico Gemelli Rome"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Cellini","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics Pediatric Neurology Unit A. 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