Ketogenic diet in action: Metabolic profiling of pyruvate dehydrogenase deficiency

Eri Ogawa; Takako Hishiki; Noriyo Hayakawa; Hisato Suzuki; Kenjiro Kosaki; Makoto Suematsu; Toshiki Takenouchi

doi:10.1016/j.ymgmr.2023.100968

Ketogenic diet in action: Metabolic profiling of pyruvate dehydrogenase deficiency

Mol Genet Metab Rep. 2023 Mar 20:35:100968. doi: 10.1016/j.ymgmr.2023.100968. eCollection 2023 Jun.

Authors

Eri Ogawa¹, Takako Hishiki², Noriyo Hayakawa^{2

3}, Hisato Suzuki⁴, Kenjiro Kosaki⁴, Makoto Suematsu^{2

5}, Toshiki Takenouchi¹

Affiliations

¹ Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
² Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan.
³ Clinical and Translational Research Center, Keio University School of Medicine, Tokyo, Japan.
⁴ Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
⁵ Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.

Abstract

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.

Keywords: Ketogenic diet; Metabolome; Pyruvate dehydrogenase deficiency; Whole genome sequencing.

Publication types

Case Reports