Teruo Miyazaki1, Hironori Nagasaka2, Haruki Komatsu3, Ayano Inui4, Ichiro Morioka5, Hirokazu Tsukahara6, Shunsaku Kaji7, Satoshi Hirayama8, Takashi Miida8, Hiroki Kondou9, Kenji Ihara10,11, Mariko Yagi12, Zenro Kizaki13, Kazuhiko Bessho14, Takahiro Kodama15, Kazumoto Iijima5, Tohru Yorifuji16, Yasushi Matsuzaki17, Akira Honda17. 1. Division of Gastroenterology, Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan. teruom@tokyo-med.ac.jp. 2. Department of Pediatrics, Takarazuka City Hospital, Takarazuka, Hyogo, Japan. 3. Department of Pediatrics, Toho University Sakura Medical Center, Chiba, Japan. 4. Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Kanagawa, Japan. 5. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. 6. Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 7. Department of Pediatrics, Tsuyama-Chuo Hospital, Tsuyama, Okayama, Japan. 8. Department of Clinical Laboratory Medicine, Juntendo University School of Medicine, Tokyo, Japan. 9. Department of Pediatrics, Kindai University Nara Hospital, Nara, Japan. 10. Department of Pediatrics, Kyushu University Graduate School of Medical Science, Fukuoka, Japan. 11. Department of Pediatrics, Faculty of Medicine, Oita University, Yufu, Oita, Japan. 12. Department of Pediatrics, Nikoniko House Medical and Welfare Center, Kobe, Hyogo, Japan. 13. Department of Pediatrics, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan. 14. Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan. 15. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka, Japan. 16. Division of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan. 17. Division of Gastroenterology, Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan.
Abstract
BACKGROUND: Citrin (mitochondrial aspartate-glutamate transporter) deficiency causes the failures in both carbohydrate-energy metabolism and the urea cycle, and the alterations in the serum levels of several amino acids in the stages of newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are resolved between the NICCD and CTLN2, but the reasons are still unclear. This study evaluated the serum amino acid profile in citrin-deficient children during the healthy stage. METHODS: Using HPLC-MS/MS analysis, serum amino acids were evaluated among 20 citrin-deficient children aged 5-13 years exhibiting normal liver function and 35 age-matched healthy controls. RESULTS: The alterations in serum amino acids characterized in the NICCD and CTLN2 stages were not observed in the citrin-deficient children. Amino acids involved in the urea cycle, including arginine, ornithine, citrulline, and aspartate, were comparable in the citrin-deficient children to the respective control levels, but serum urea was twofold higher, suggestive of a functional urea cycle. The blood sugar level was normal, but glucogenic amino acids and glutamine were significantly decreased in the citrin-deficient children compared to those in the controls. In addition, significant increases of ketogenic amino acids, branched-chain amino acids (BCAAs), a valine intermediate 3-hydroxyisobutyrate, and β-alanine were also found in the citrin-deficient children. CONCLUSION: The profile of serum amino acids in the citrin-deficient children during the healthy stage showed different characteristics from the NICCD and CTLN2 stages, suggesting that the failures in both urea cycle function and energy metabolism might be compensated by amino acid metabolism. SYNOPSIS: In the citrin-deficient children during the healthy stage, the characteristics of serum amino acids, including decrease of glucogenic amino acids, and increase of ketogenic amino acids, BCAAs, valine intermediate, and β-alanine, were found by comparison to the age-matched healthy control children, and it suggested that the characteristic alteration of serum amino acids may be resulted from compensation for energy metabolism and ammonia detoxification.
BACKGROUND:Citrin (mitochondrial aspartate-glutamate transporter) deficiency causes the failures in both carbohydrate-energy metabolism and the urea cycle, and the alterations in the serum levels of several amino acids in the stages of newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are resolved between the NICCD and CTLN2, but the reasons are still unclear. This study evaluated the serum amino acid profile in citrin-deficient children during the healthy stage. METHODS: Using HPLC-MS/MS analysis, serum amino acids were evaluated among 20 citrin-deficient children aged 5-13 years exhibiting normal liver function and 35 age-matched healthy controls. RESULTS: The alterations in serum amino acids characterized in the NICCD and CTLN2 stages were not observed in the citrin-deficient children. Amino acids involved in the urea cycle, including arginine, ornithine, citrulline, and aspartate, were comparable in the citrin-deficient children to the respective control levels, but serum urea was twofold higher, suggestive of a functional urea cycle. The blood sugar level was normal, but glucogenic amino acids and glutamine were significantly decreased in the citrin-deficient children compared to those in the controls. In addition, significant increases of ketogenic amino acids, branched-chain amino acids (BCAAs), a valine intermediate 3-hydroxyisobutyrate, and β-alanine were also found in the citrin-deficient children. CONCLUSION: The profile of serum amino acids in the citrin-deficient children during the healthy stage showed different characteristics from the NICCD and CTLN2 stages, suggesting that the failures in both urea cycle function and energy metabolism might be compensated by amino acid metabolism. SYNOPSIS: In the citrin-deficient children during the healthy stage, the characteristics of serum amino acids, including decrease of glucogenic amino acids, and increase of ketogenic amino acids, BCAAs, valine intermediate, and β-alanine, were found by comparison to the age-matched healthy control children, and it suggested that the characteristic alteration of serum amino acids may be resulted from compensation for energy metabolism and ammonia detoxification.
Entities:
Keywords:
Age-matched control study; Amino acids; Energy metabolism; Gluconeogenesis; Mitochondria transporter; Urea cycle