{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T06:55:34Z","timestamp":1769842534432,"version":"3.49.0"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The association between dystonia and early-onset epileptic encephalopathy (EOEE) may have a genetic basis. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) germline mutations have been described in the last decade and associated with refractory EOEEs. Dysmorphisms and visceral abnormalities have also been reported. Here, we present the case of a now 8-month-old child who was evaluated for dystonia, visual impairment, and developmental delay at 2 months of age, followed by refractory focal seizures when he was 4 months old. The remaining examination was normal, besides an accelerated linear growth. His brain magnetic resonance and an extensive metabolic investigation failed to show any abnormalities. At 7 months of age, the exome sequencing found a hemizygous PIGA pathogenic variant-c.1352T\u2009&gt;\u2009C (p.(Ile451Thr). Seizures improved after the association of carbamazepine with levetiracetam and the beginning of the ketogenic diet. To our knowledge, this is the first time the phenotype associated with this specific mutation is described. Our patient had the singularity of manifesting with remarkable dystonia, over 2 months before the onset of seizures. We also point to the utility of the gene sequencing approach in the diagnosis of patients with dystonia and EOEEs, since identification of the genetic cause may help in patient's management and families' empowerment.<\/jats:p>","DOI":"10.1055\/a-2239-1985","type":"journal-article","created":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:34:52Z","timestamp":1704501292000},"page":"265-268","source":"Crossref","is-referenced-by-count":2,"title":["Early-Onset Dystonia and Visual Impairment Preceding Epileptic Encephalopathy Associated with PIGA Gene Mutation"],"prefix":"10.1055","volume":"55","author":[{"given":"Catarina","family":"Franquelim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Garcia de Orta, Almada, Portugal"}]},{"given":"Andreia","family":"Romana","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Garcia de Orta, Almada, Portugal"}]},{"given":"Augusto","family":"Rach\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Garcia de Orta, Almada, Portugal"}]},{"given":"Joana Sousa","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Garcia de Orta, Almada, Portugal"}]},{"given":"Jos\u00e9 Paulo","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro de Desenvolvimento da Crian\u00e7a, Hospital Garcia de Orta, Almada, Portugal"}]},{"given":"Jo\u00e3o","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro de Desenvolvimento da Crian\u00e7a, Hospital Garcia de Orta, Almada, Portugal"}]}],"member":"194","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"issue":"07","key":"ref1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/mds.25475","article-title":"Phenomenology and classification of dystonia: a consensus update","volume":"28","author":"A Albanese","year":"2013","journal-title":"Mov Disord"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.pediatrneurol.2020.12.001","article-title":"Early-onset developmental and epileptic encephalopathies of infancy: an overview of the genetic basis and clinical features","volume":"116","author":"N Morrison-Levy","year":"2021","journal-title":"Pediatr Neurol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13023-015-0243-8","article-title":"The genotypic and phenotypic spectrum of PIGA deficiency","volume":"10","author":"M Tarailo-Graovac","year":"2015","journal-title":"Orphanet J Rare Dis"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ajhg.2011.11.031","article-title":"The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria","volume":"90","author":"J J Johnston","year":"2012","journal-title":"Am J Hum Genet"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1111\/epi.16545","article-title":"Lessons learned from 40 novel PIGA patients and a review of the literature","volume":"61","author":"A Bayat","year":"2020","journal-title":"Epilepsia"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ejpn.2020.06.002","article-title":"Early-onset epileptic encephalopathy related to germline PIGA mutations: a series of 5 cases","volume":"28","author":"S Cabasson","year":"2020","journal-title":"Eur J Paediatr Neurol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"758899","DOI":"10.3389\/fneur.2021.758899","article-title":"Spectrum of neurological symptoms in glycosylphosphatidylinositol biosynthesis defects: systematic review","volume":"12","author":"J Paprocka","year":"2022","journal-title":"Front Neurol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.seizure.2018.03.025","article-title":"A novel PIGA mutation in a Taiwanese family with early-onset epileptic encephalopathy","volume":"58","author":"W D Lin","year":"2018","journal-title":"Seizure"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1159\/000505797","article-title":"A Novel Mutation in PIGA associated with multiple congenital anomalies-hypotonia-seizure syndrome 2 (MCAHS2) in a boy with a combination of severe epilepsy and gingival hyperplasia","volume":"11","author":"C M Neuhofer","year":"2020","journal-title":"Mol Syndromol"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13023-020-01401-z","article-title":"The glycosylphosphatidylinositol biosynthesis pathway in human diseases","volume":"15","author":"T Wu","year":"2020","journal-title":"Orphanet J Rare Dis"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.seizure.2018.01.013","article-title":"A novel PIGA variant associated with severe X-linked epilepsy and profound developmental delay","volume":"56","author":"K J Low","year":"2018","journal-title":"Seizure"},{"issue":"08","key":"ref12","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.braindev.2016.02.008","article-title":"A novel PIGA mutation in a family with X-linked, early-onset epileptic encephalopathy","volume":"38","author":"Y O Kim","year":"2016","journal-title":"Brain Dev"},{"issue":"18","key":"ref13","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1212\/WNL.0000000000000389","article-title":"PIGA mutations cause early-onset epileptic encephalopathies and distinctive features","volume":"82","author":"M Kato","year":"2014","journal-title":"Neurology"},{"issue":"09","key":"ref14","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.braindev.2016.04.004","article-title":"Ketogenic diet\u2014a novel treatment for early epileptic encephalopathy due to PIGA deficiency","volume":"38","author":"C Joshi","year":"2016","journal-title":"Brain Dev"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"106530","DOI":"10.1016\/j.eplepsyres.2020.106530","article-title":"Deciphering the premature mortality in PIGA-CDG\u2014an untold story","volume":"170","author":"A Bayat","year":"2021","journal-title":"Epilepsy Res"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2239-1985.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T16:42:00Z","timestamp":1730824920000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2239-1985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,5]]},"references-count":15,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2024,7,12]]},"published-print":{"date-parts":[[2024,8]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2239-1985","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1,5]]},"published":{"date-parts":[[2024,1,5]]}}}