{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T08:40:54Z","timestamp":1774514454043,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive neurometabolic disorder caused by biallelic pathogenic variants in\n                    <jats:italic>ALDH5A1<\/jats:italic>\n                    , encoding the mitochondrial enzyme SSADH. This enzyme catalyses the conversion of succinic semialdehyde to succinic acid in the \u03b3\u2010aminobutyric acid (GABA) degradation pathway. SSADH deficiency leads to the accumulation of neurotoxic metabolites, including \u03b3\u2010hydroxybutyrate (GHB), and presents with developmental delay, hypotonia, ataxia, seizures, behavioral disturbances, and intellectual disability. We report a 10\u2010month\u2010old Caucasian male with global developmental delay, central hypotonia, and delayed motor milestones. He presented acutely with left\u2010sided hemiplegia following irritability and vomiting. Brain MRI showed bilateral (right\u2009&gt;\u2009left) T2 hyperintensities and diffusion restriction in the globus pallidus. Urine organic acid analysis via gas chromatography\u2013mass spectrometry revealed markedly elevated 4\u2010hydroxybutyric acid and 4,5\u2010dihydroxyhexanoic lactone, pathognomonic for SSADH deficiency. Molecular testing identified compound heterozygous\n                    <jats:italic>ALDH5A1<\/jats:italic>\n                    variants: c.278G&gt;T p.(Cys93Phe) and c.612G&gt;A p.(Trp204*), both previously reported as pathogenic. Parental segregation confirmed trans configuration. Three weeks postillness, he developed focal seizures, which have remained well controlled on levetiracetam. His seizure onset in infancy is notably earlier than the typical early childhood onset (~9\u2009years) reported in SSADH deficiency. This case expands the phenotypic spectrum of SSADH deficiency to include metabolic stroke as a presenting feature in infancy and highlights the importance of early recognition and molecular confirmation to guide management and emerging therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/jmd2.70071","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T01:44:12Z","timestamp":1769996652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Stroke: Atypical Presentation of Succinic Semialdehyde Dehydrogenase Deficiency"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4664-0690","authenticated-orcid":false,"given":"Sharmila","family":"Kiss","sequence":"first","affiliation":[{"name":"Department of Metabolic Medicine The Royal Children's Hospital  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Leventer","sequence":"additional","affiliation":[{"name":"Department of Neurology The Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Victorian Clinical Genetics Services, Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1269-0558","authenticated-orcid":false,"given":"Cormac","family":"Duff","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine The Royal Children's Hospital  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9894-4610","authenticated-orcid":false,"given":"Emma","family":"Macdonald\u2010Laurs","sequence":"additional","affiliation":[{"name":"Department of Neurology The Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"},{"name":"Neuroscience Stream, Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia\u2010Paris","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Neurology The Royal Children's Hospital  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4134-3531","authenticated-orcid":false,"given":"Fahaz","family":"Nazer","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services, Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8984-4880","authenticated-orcid":false,"given":"Michelle","family":"Cao","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services, Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abisha","family":"Srikumar","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services, Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenzen","family":"Dalina","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services, Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Eggington","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services, Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6158-6215","authenticated-orcid":false,"given":"Joy Yaplito\u2010","family":"Lee","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services, Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2016.06.009"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12723"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1405468"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000059549.70717.80"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-019-0821-z"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-024-09538-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020477"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073821991295"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10629"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073810368137"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-015-2942-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3470"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/aian.AIAN_213_18"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073820981262"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-024-01925-4"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108363"},{"key":"e_1_2_11_18_1","volume-title":"Succinic Semialdehyde Dehydrogenase Deficiency","author":"Sergi C.","year":"2024"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.2478\/bjmg-2023-0008"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10626"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70071","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.70071","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T07:20:12Z","timestamp":1774509612000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.70071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,1]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/jmd2.70071"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.70071","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,1]]},"assertion":[{"value":"2025-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70071"}}