Ogawa Eri, Hishiki Takako, Hayakawa Noriyo, Suzuki Hisato, Kosaki Kenjiro, Suematsu Makoto, Takenouchi Toshiki
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan.
Mol Genet Metab Rep. 2023 Mar 20;35:100968. doi: 10.1016/j.ymgmr.2023.100968. eCollection 2023 Jun.
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.
丙酮酸脱氢酶复合体是胞质糖酵解与线粒体内三羧酸循环之间的主要连接环节。一名丙酮酸脱氢酶复合体缺乏症婴儿接受了维生素B1补充治疗和生酮饮食。这些饮食调整解决了肾小管重吸收、中枢性呼吸暂停和输血依赖型贫血问题。同时进行的代谢组分析表明，氨基酸尿症得到缓解，三羧酸循环中底物总量增加，这反映了线粒体能量代谢的改善。在生酮比例提高到3:1后，脑脊液中首次检测到谷氨酸，同时临床症状有所改善；因此，脑脊液中的谷氨酸水平可能代表神经元恢复的生物标志物。体液的代谢组分析有助于监测先天性碳水化合物代谢缺陷婴儿的治疗效果。
