TY - JOUR
T1 - Ketogenic diet in action
T2 - Metabolic profiling of pyruvate dehydrogenase deficiency
AU - Ogawa, Eri
AU - Hishiki, Takako
AU - Hayakawa, Noriyo
AU - Suzuki, Hisato
AU - Kosaki, Kenjiro
AU - Suematsu, Makoto
AU - Takenouchi, Toshiki
N1 - Funding Information:
This research was supported by Japan Agency for Medical Research and Development under Grant Number JP22gk0110038 (to TT), Japan Foundation for Pediatric Research , Grant No. 21-007 (to TT), Keio Gijuku Academic Development Funds (to TT), Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics (to TT), Japan Society for the Promotion of Science under Grant-in-Aid for Challenging Exploratory Research , Grant Number JP22K19494 , and Mother and Child Health Foundation (to TT). This research was also supported by World Premier Institute of BioQ2 for Keio University (to MS), and Japan Agency for Medical Research and Development - Moonshot Project for Microbiome (to MS).
Publisher Copyright:
© 2023 The Authors
PY - 2023/6
Y1 - 2023/6
N2 - The pyruvate dehydrogenase complex serves as the main connection between cytosolic glycolysis and the tricarboxylic acid cycle within mitochondria. An infant with pyruvate dehydrogenase complex deficiency was treated with vitamin B1 supplementation and a ketogenic diet. These dietary modifications resolved the renal tubular reabsorption, central apnea, and transfusion-dependent anemia. A concurrent metabolome analysis demonstrated the resolution of the amino aciduria and an increased total amount of substrates in the tricarboxylic acid cycle, reflecting the improved mitochondrial energetics. Glutamate was first detected in the cerebrospinal fluid, accompanied by a clinical improvement, after the ketogenic ratio was increased to 3:1; thus, glutamate levels in cerebrospinal fluid may represent a biomarker for neuronal recovery. Metabolomic analyses of body fluids are useful for monitoring therapeutic effects in infants with inborn errors of carbohydrate metabolism.
AB - The pyruvate dehydrogenase complex serves as the main connection between cytosolic glycolysis and the tricarboxylic acid cycle within mitochondria. An infant with pyruvate dehydrogenase complex deficiency was treated with vitamin B1 supplementation and a ketogenic diet. These dietary modifications resolved the renal tubular reabsorption, central apnea, and transfusion-dependent anemia. A concurrent metabolome analysis demonstrated the resolution of the amino aciduria and an increased total amount of substrates in the tricarboxylic acid cycle, reflecting the improved mitochondrial energetics. Glutamate was first detected in the cerebrospinal fluid, accompanied by a clinical improvement, after the ketogenic ratio was increased to 3:1; thus, glutamate levels in cerebrospinal fluid may represent a biomarker for neuronal recovery. Metabolomic analyses of body fluids are useful for monitoring therapeutic effects in infants with inborn errors of carbohydrate metabolism.
KW - Ketogenic diet
KW - Metabolome
KW - Pyruvate dehydrogenase deficiency
KW - Whole genome sequencing
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U2 - 10.1016/j.ymgmr.2023.100968
DO - 10.1016/j.ymgmr.2023.100968
M3 - Article
AN - SCOPUS:85150444656
SN - 2214-4269
VL - 35
JO - Molecular Genetics and Metabolism Reports
JF - Molecular Genetics and Metabolism Reports
M1 - 100968
ER -