Intravenous ketogenic diet therapy for neonatal-onset pyruvate dehydrogenase complex deficiency

Takehiko Inui, Yoichi Wada, Moriei Shibuya, Natsuko Arai-Ichinoi, Yukimune Okubo, Wakaba Endo, Toshihiko Uchida, Noriko Togashi, Etsuo Naito, Kazuhiro Haginoya

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Background: Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that causes lactic acidosis and neurodevelopmental changes. Five causative genes have been identified: PDHA1, PDHB, DLAT, DLD, and PDHX. Four neurological phenotypes have been reported: neonatal encephalopathy with lactic acidosis, non-progressive infantile encephalopathy, Leigh syndrome, and relapsing ataxia. Of these, neonatal encephalopathy has the worst mortality and morbidity and there is no effective treatment. Subjects and methods: We studied two girls who were clinically diagnosed with PDHC deficiency as neonates; they were subsequently found to have PDHA1 mutations. The clinical diagnosis was based on white matter loss and a lateral ventricular septum on fetal MRI, spasticity of the lower extremities, and lactic acidosis worsening after birth. Intravenous ketogenic diets were started within 24 h after birth. The ketogenic ratio was increased until the blood lactate level was controlled, while monitoring for side effects. Results: In both cases, the lactic acidosis improved immediately with no apparent side effects. Both children had better developmental outcomes than previously reported cases; neither exhibited epilepsy. Conclusions: Intravenous ketogenic diet therapy is a treatment option for neonatal-onset PDHC deficiency. Further studies are needed to optimize this therapy.

Original languageEnglish
Pages (from-to)244-248
Number of pages5
JournalBrain and Development
Issue number3
Publication statusPublished - 2022 Mar


  • Genetics
  • Inborn error of metabolism
  • Intravenous ketogenic diet therapy
  • Ketogenic diet therapy
  • Lactic acidosis
  • Neonatology
  • Nutrition therapy
  • Prenatal diagnosis
  • Pyruvate dehydrogenase complex deficiency


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