{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:50:08Z","timestamp":1790419808882,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Adenylosuccinate lyase (ADSL) deficiency is a rare inherited metabolic disorder with a wide phenotypic presentation, classically grouped into three types (neonatal, type I, and type II). We aim to better delineate the pathological spectrum, focusing on the electroclinical characteristics and phenotypic differences of patients with ADSL deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Seven patients, from four different families, underwent serial electroencephalogram (EEG), clinical assessment, and neuroimaging. We also performed a systematic review of the cases published in the literature, summarizing the available clinical, neurophysiological, and genetic data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report seven previously unreported ADSL deficiency patients with long\u2010term follow\u2010up (10\u201334\u2009years). From the literature review, we collected 81 previously reported cases. Of the included patient population, 58 % (51\/88) were classified as having ADSL deficiency type I, 28% (25\/88) as having type II, and 14% (12\/88) as having neonatal. The most frequently reported pathogenic variants are p.R426H homozygous (19 patients), p.Y114H in compound heterozygosity (13 patients), and p.D430N homozygous (6 patients). In the majority (89.2%), disease onset was within the first year of life. Epilepsy is present in 81.8% of the patients, with polymorphic and often intractable seizures. EEG features seem to display common patterns and developmental trajectories: (i) poor general background organization with theta\u2010delta activity; (ii) hypsarrhythmia with spasms, usually adrenocorticotropic hormone\u2010responsive; (iii) generalized epileptic discharges with frontal or frontal temporal predominance; and (iv) epileptic discharge activation in sleep with an altered sleep structure. Imaging features present consistent findings of cerebral atrophy with frontal predominance, cerebellar atrophy, and white matter abnormalities among the three types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>ADSL deficiency presents variable phenotypic expression, whose severity could be partially attributed to residual activity of the mutant protein. Although a precise phenotype\u2010genotype correlation was not yet feasible, we delineated a common pattern of clinical, neuroradiological, and neurophysiological features.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12837","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T10:30:35Z","timestamp":1697452235000},"page":"106-121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Electroclinical features and phenotypic differences in adenylosuccinate lyase deficiency: Long\u2010term follow\u2010up of seven patients from four families and appraisal of the literature"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-8280","authenticated-orcid":false,"given":"Gianni","family":"Cutillo","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Pediatric Neurology Unit Buzzi Children's Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3850-8849","authenticated-orcid":false,"given":"Silvia","family":"Masnada","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Pediatric Neurology Unit Buzzi Children's Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-9492","authenticated-orcid":false,"given":"Gaetan","family":"Lesca","sequence":"additional","affiliation":[{"name":"Department of Genetics Lyon University Hospitals  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9432-4409","authenticated-orcid":false,"given":"Doroth\u00e9e","family":"Ville","sequence":"additional","affiliation":[{"name":"Derpartment of Pediatric Neurology Lyon University Hospital  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Accorsi","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatric Division Spedali Civili  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatric Division Spedali Civili  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[{"name":"Neuroradiology Department IRCCS C.Mondino National Neurological Institute  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialuisa","family":"Valente","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit, Medical Genetics Section SS. Annunziata Hospital  Taranto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Borrelli","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, Laboratory of Biostatistics University \u201cG. D'Annunzio\u201d  Pescara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavia Eleonora","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, Unit of Biostatistics and Clinical Epidemiology University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2851-3441","authenticated-orcid":false,"given":"Pierangelo","family":"Veggiotti","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Pediatric Neurology Unit Buzzi Children's Hospital  Milan Italy"},{"name":"Department of Biomedical and Clinical Sciences University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9755-y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(84)91505-8"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2016.07.007"},{"key":"e_1_2_11_5_1","first-page":"50","article-title":"Attenuated adenylosuccinate lyase deficiency: a report of one case and a review of the literature","volume":"45","author":"Jurecka A","year":"2014","journal-title":"Neuropediatrics"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2006.09.027"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307380101600501"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.10.1501"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01731-6"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1999)13:3<197::AID-HUMU3>3.0.CO;2-D"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20176"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01637-z"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073811424465"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.23852"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(00)00154-6"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2010.06.007"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2019.100502"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-011-1503-9"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/ejpn.1999.0172"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2011.08.008"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12244"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12837","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T06:47:05Z","timestamp":1707288425000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,27]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/epi4.12837"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12837","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,27]]},"assertion":[{"value":"2023-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}