{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:52:53Z","timestamp":1755798773064,"version":"3.44.0"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Child Neurology Society"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We present the cases of two sisters, both harboring the same <jats:italic>ALDH18A1<\/jats:italic> gene mutations, who presented with a complex clinical phenotype characterized by spastic paraparesis with ataxia, epileptic encephalopathy, severe psychomotor deficits, and behavioral abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Case description of two sisters with <jats:italic>ALDH18A1<\/jats:italic> gene mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The older patient, a 12\u2010year\u2010old girl, exhibited spastic paraparesis with ataxia, microcephaly, facial dysmorphisms, and severe intellectual disability, with an absence of verbal language. An electroencephalogram (EEG) revealed marked spike\u2010and\u2010wave activation during sleep (SWAS), although no clinically documented seizures were observed. The younger sister, who was 9 years old, displayed a similar clinical presentation, including spastic paraparesis with ataxia, microcephaly, dysmorphisms, however, she displayed slightly more severe intellectual deficits and polymorphic seizures. EEG revealed a SWAS pattern in this case. Magnetic resonance imaging scans in both cases showed only a thin corpus callosum. Whole exome sequencing unveiled the presence of two likely pathogenic variants in compound heterozygosity within the <jats:italic>ALDH18A1<\/jats:italic> gene. Specifically, these variants included the splice site variant c.88 + 1c.88+1G&gt;A of paternal origin and the variant c.1364c.1364T&gt;C (p.Leu455Ser) of maternal origin. Both sisters displayed normal blood levels of ammonia, ornithine, citrulline, arginine, and other amino acids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These findings were compatible with <jats:italic>ALDH18A1<\/jats:italic>\u2010related HSP complicated with a clinical and EEG pattern reminiscent of DEE\u2010SWAS. We present the first report of DEE\u2010SWAS in <jats:italic>ALDH18A1<\/jats:italic>\u2010related HSP, expanding the clinical manifestations of this complex neurodevelopmental condition.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cns3.20056","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T02:04:05Z","timestamp":1707357845000},"page":"73-78","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>ALDH18A1<\/i>\u2010related hereditary spastic paraplegia and developmental and epileptic encephalopathy with spike\u2010wave activation in sleep: Expanding the clinical phenotype"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4863-5029","authenticated-orcid":false,"given":"Giusi","family":"Ferrara","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology Buzzi Children's Hospital, ASST\u2010FBF\u2010Sacco Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-8280","authenticated-orcid":false,"given":"Gianni","family":"Cutillo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Buzzi Children's Hospital, ASST\u2010FBF\u2010Sacco Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Peterlongo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Buzzi Children's Hospital, ASST\u2010FBF\u2010Sacco Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Minacapilli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Buzzi Children's Hospital, ASST\u2010FBF\u2010Sacco Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Iascone","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory ASST Papa Giovanni XXIII 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