{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:39:50Z","timestamp":1790969990243,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RDCRN 5U54NS078059\u201005 project NAMDC 7413 grant"],"award-info":[{"award-number":["RDCRN 5U54NS078059\u201005 project NAMDC 7413 grant"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012729","name":"Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University","doi-asserted-by":"publisher","award":["05496"],"award-info":[{"award-number":["05496"]}],"id":[{"id":"10.13039\/100012729","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Congenital lactic acidosis due to pyruvate dehydrogenase phosphatase (PDP) deficiency is very rare. PDP regulates pyruvate dehydrogenase complex (PDC) and defective PDP leads to PDC deficiency. We report a case with functional PDC deficiency with low activated (+dichloroacetate) and inactivated (+fluoride) PDC activities in lymphocytes and fibroblasts, normal activity of other mitochondrial enzymes in fibroblasts, and novel biallelic frameshift mutation in the <jats:italic>PDP1<\/jats:italic> gene, c.575dupT (p.L192FfsX5), with absent PDP1 product in fibroblasts. Unexpectedly, the patient also had low branched\u2010chain 2\u2010ketoacid dehydrogenase (BCKDH) activity in fibroblasts with slight elevation of branched\u2010chain amino acids in plasma and ketoacids in urine but with no pathogenic mutations in the enzymes of BCKDH, which could suggest shared regulatory function of PDC and BCKDH in fibroblasts, potentially in other tissues or cell types as well, but this remains to be determined. The clinical presentation of this patient overlaps that of other patients with primary\u2010specific PDC deficiency, with neonatal\/infantile and childhood lactic acidosis, normal lactate to pyruvate ratio, elevated plasma alanine, delayed psychomotor development, epileptic encephalopathy, feeding difficulties, and hypotonia. This patient exhibited marked improvement of overall development following initiation of ketogenic diet at 31\u2009months of age. To the best of our knowledge, this is the fourth case of functional PDC deficiency with a defined mutation in <jats:italic>PDP1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Synopsis<\/jats:title><jats:p>Pyruvate dehydrogenase phosphatase (PDP) regulates pyruvate dehydrogenase complex (PDC) and defective PDP due to <jats:italic>PDP1<\/jats:italic> mutations leads to PDC deficiency and congenital lactic acidosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmd2.12054","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T18:43:27Z","timestamp":1560797007000},"page":"26-35","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (<i>PDP1<\/i>) causing pyruvate dehydrogenase complex deficiency"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-6877","authenticated-orcid":false,"given":"Jirair K.","family":"Bedoyan","sequence":"first","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University (CWRU)  Cleveland Ohio"},{"name":"Pediatrics Case Western Reserve University (CWRU)  Cleveland Ohio"},{"name":"Center for Human Genetics University Hospitals Cleveland Medical Center (UHCMC)  Cleveland Ohio"},{"name":"Center for Inherited Disorders of Energy Metabolism (CIDEM) University Hospitals Cleveland Medical Center (UHCMC)  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Hecht","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, The Manton Center for Orphan Disease Research Boston Children's Hospital, Harvard Medical School  Boston 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Hospital, Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Yang","sequence":"additional","affiliation":[{"name":"Radiology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Kyung","family":"Shin","sequence":"additional","affiliation":[{"name":"School of Medicine Case Western Reserve University (CWRU)  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Grahame","sequence":"additional","affiliation":[{"name":"Center for Inherited Disorders of Energy Metabolism (CIDEM) University Hospitals Cleveland Medical Center (UHCMC)  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne D.","family":"DeBrosse","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University (CWRU)  Cleveland 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