{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T05:08:23Z","timestamp":1768626503307,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pyruvate carboxylase is a mitochondrial enzyme essential for the tricarboxylic acid cycle (TCA), gluconeogenesis and fatty\u2010acid synthesis. Pyruvate carboxylase deficiency (PCD) mostly presents with life\u2010limiting encephalopathy (types A\/B). A milder type C presentation is rare, with a comparatively favourable prognosis. Therapies remain essentially supportive. Triheptanoin is an odd\u2010chain triglyceride, with the potential to replenish TCA intermediates (anaplerosis), and its metabolites cross the blood\u2013brain\u2010barrier. Outcomes of triheptanoin treatment in PCD types A\/B have been disappointing, but have not been reported in type C. Here, we present two new patients with PCD type C, and report the response to treatment with triheptanoin in one. Patient 1 (P1) presented with neonatal\u2010onset lactic acidosis and recurrent symptomatic lactic acidosis following exercise and during illnesses, with frequent hospitalisations. Speech development was delayed. MRI\u2010brain showed delayed cerebral myelination. Patient 2 (P2) presented with episodic ketoacidosis, hyperlactataemia and hypoglycaemia at 2\u2009years of age, with gross motor delay and mild global volume loss on MRI brain. Treatment with triheptanoin was commenced in P1 at 3\u2009years of age with up\u2010titration to 35\u2009mL\/day (25% of daily energy intake) over 6 months, due to transient diarrhoea. Dietary long\u2010chain triglycerides were restricted, with fat\u2010soluble vitamin supplementation. Subsequently, hospitalisations during intercurrent illnesses decreased, post\u2010exertional hyperlactataemia resolved and exercise tolerance improved. Continued developmental progress was observed, and repeat MRI 18\u2009months after initiation showed improved myelination. Triheptanoin was well\u2010tolerated and appeared efficacious during 2\u2009years' follow\u2010up, and has potential to restore energy homeostasis and myelin synthesis in PCD type C.<\/jats:p>","DOI":"10.1002\/jmd2.12405","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:54:06Z","timestamp":1703811246000},"page":"10-16","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pyruvate carboxylase deficiency type C; variable presentation and beneficial effect of triheptanoin"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9368-9887","authenticated-orcid":false,"given":"I.","family":"Bernhardt","sequence":"first","affiliation":[{"name":"Department of Paediatric Metabolic Medicine Great Ormond Street Hospital for Children  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Van Dorp","sequence":"additional","affiliation":[{"name":"Dietetics Department Great Ormond Street Hospital for Children  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Dietetics Department Great Ormond Street Hospital for Children  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"McSweeney","sequence":"additional","affiliation":[{"name":"Department of Paediatric Metabolic Medicine Great Ormond Street Hospital for Children  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Metabolic Medicine Great Ormond Street Hospital for Children  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Baruteau","sequence":"additional","affiliation":[{"name":"Department of Paediatric Metabolic Medicine Great Ormond Street Hospital for Children  London UK"},{"name":"Great Ormond Street Institute of Child Health, University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Chakrapani","sequence":"additional","affiliation":[{"name":"Department of Paediatric Metabolic Medicine Great Ormond Street Hospital for Children  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.05.004"},{"key":"e_1_2_11_3_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Wang 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Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T02:07:06Z","timestamp":1705630026000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,28]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/jmd2.12405"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12405","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,28]]},"assertion":[{"value":"2023-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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