{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:00:57Z","timestamp":1785578457940,"version":"3.56.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Pyruvate dehydrogenase complex (PDC) deficiency is a rare mitochondrial disorder characterized by impaired oxidative metabolism, predominantly due to pathogenic variants in the\n                    <jats:italic toggle=\"yes\">PDHA1<\/jats:italic>\n                    gene. We present the clinical, biochemical, radiologic, and molecular characterization of 4 Argentine pediatric patients with\n                    <jats:italic toggle=\"yes\">PDHA1<\/jats:italic>\n                    -related PDC deficiency, including a novel missense variant, c.260T&gt;C p.(Ile87Thr). Clinical presentations ranged from severe neonatal encephalopathy with central apneas to a more slowly progressive neurodegenerative course in childhood. All patients exhibited lactic acidosis and structural brain abnormalities, with 3 fulfilling criteria for Leigh syndrome. Molecular studies identified 4 missense variants located in conserved regions of the E1\u03b1 subunit. In silico analysis of the novel p.(Ile87Thr) variant suggested impaired thiamine pyrophosphate binding. All patients received thiamine and a ketogenic diet, with favorable outcomes in seizure control, neurodevelopment, and metabolic stability. Our findings expand the clinical and molecular spectrum of\n                    <jats:italic toggle=\"yes\">PDHA1<\/jats:italic>\n                    -related PDC deficiency and underscore the importance of early diagnosis and targeted metabolic therapy. Furthermore, we report a previously undescribed radiologic pattern in one patient and propose potential structural implications of the novel variant based on protein modeling.\n                  <\/jats:p>","DOI":"10.1177\/08830738251404115","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T15:28:07Z","timestamp":1766503687000},"page":"1119-1131","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["From Severe Neonatal Encephalopathy to Slowly Neurologic Progressive Disease: Pyruvate Dehydrogenase Deficiency Related to\n                    <i>PDHA1<\/i>\n                    Variants"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0721-8781","authenticated-orcid":false,"given":"Sofia","family":"Corbaz","sequence":"first","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6336-491X","authenticated-orcid":false,"given":"Daniela Alejandra","family":"Pibernus","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Amina","family":"Loos","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Mercedes","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Celeste","family":"Buompadre","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Mart\u00edn","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Paula","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Rugilo","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Armeno","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go Hun","family":"Seo","sequence":"additional","affiliation":[{"name":"3billion Inc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rin","family":"Khang","sequence":"additional","affiliation":[{"name":"3billion Inc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Noemi","family":"Alonso","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1080-9969","authenticated-orcid":false,"given":"Hilda Ver\u00f3nica","family":"Ar\u00e1oz","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan,\u201d Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"e_1_3_3_2_2","volume-title":"GeneReviews\u00ae","author":"Ganetzky R","year":"2021","unstructured":"Ganetzky R, McCormick EM, Falk MJ. Primary pyruvate dehydrogenase complex deficiency overview. In: Adam MP, Feldman J, Mirzaa GM, et al., eds. GeneReviews\u00ae. 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