Serum amino acid profiling in citrin-deficient children exhibiting normal liver function during the apparently healthy period

Teruo Miyazaki, Hironori Nagasaka, Haruki Komatsu, Ayano Inui, Ichiro Morioka, Hirokazu Tsukahara, Shunsaku Kaji, Satoshi Hirayama, Takashi Miida, Hiroki Kondou, Kenji Ihara, Mariko Yagi, Zenro Kizaki, Kazuhiko Bessho, Takahiro Kodama, Kazumoto Iijima, Tohru Yorifuji, Yasushi Matsuzaki, Akira Honda

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

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.

Original languageEnglish
Title of host publicationJIMD Reports
PublisherSpringer
Pages53-61
Number of pages9
DOIs
Publication statusPublished - Jan 1 2019

Publication series

NameJIMD Reports
Volume43
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312

Fingerprint

Liver
Amino Acids
Serum
Urea
Branched Chain Amino Acids
Energy Metabolism
Valine
Alanine
Amino acids
citrin
Amino Acid Transport System X-AG
Citrulline
Detoxification
Ornithine
Level control
Glutamine
Ammonia
Metabolism
Aspartic Acid
Carbohydrate Metabolism

Keywords

  • Age-matched control study
  • Amino acids
  • Energy metabolism
  • Gluconeogenesis
  • Mitochondria transporter
  • Urea cycle

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

Cite this

Miyazaki, T., Nagasaka, H., Komatsu, H., Inui, A., Morioka, I., Tsukahara, H., ... Honda, A. (2019). Serum amino acid profiling in citrin-deficient children exhibiting normal liver function during the apparently healthy period. In JIMD Reports (pp. 53-61). (JIMD Reports; Vol. 43). Springer. https://doi.org/10.1007/8904_2018_99

Serum amino acid profiling in citrin-deficient children exhibiting normal liver function during the apparently healthy period. / Miyazaki, Teruo; Nagasaka, Hironori; Komatsu, Haruki; Inui, Ayano; Morioka, Ichiro; Tsukahara, Hirokazu; Kaji, Shunsaku; Hirayama, Satoshi; Miida, Takashi; Kondou, Hiroki; Ihara, Kenji; Yagi, Mariko; Kizaki, Zenro; Bessho, Kazuhiko; Kodama, Takahiro; Iijima, Kazumoto; Yorifuji, Tohru; Matsuzaki, Yasushi; Honda, Akira.

JIMD Reports. Springer, 2019. p. 53-61 (JIMD Reports; Vol. 43).

Research output: Chapter in Book/Report/Conference proceedingChapter

Miyazaki, T, Nagasaka, H, Komatsu, H, Inui, A, Morioka, I, Tsukahara, H, Kaji, S, Hirayama, S, Miida, T, Kondou, H, Ihara, K, Yagi, M, Kizaki, Z, Bessho, K, Kodama, T, Iijima, K, Yorifuji, T, Matsuzaki, Y & Honda, A 2019, Serum amino acid profiling in citrin-deficient children exhibiting normal liver function during the apparently healthy period. in JIMD Reports. JIMD Reports, vol. 43, Springer, pp. 53-61. https://doi.org/10.1007/8904_2018_99
Miyazaki T, Nagasaka H, Komatsu H, Inui A, Morioka I, Tsukahara H et al. Serum amino acid profiling in citrin-deficient children exhibiting normal liver function during the apparently healthy period. In JIMD Reports. Springer. 2019. p. 53-61. (JIMD Reports). https://doi.org/10.1007/8904_2018_99
Miyazaki, Teruo ; Nagasaka, Hironori ; Komatsu, Haruki ; Inui, Ayano ; Morioka, Ichiro ; Tsukahara, Hirokazu ; Kaji, Shunsaku ; Hirayama, Satoshi ; Miida, Takashi ; Kondou, Hiroki ; Ihara, Kenji ; Yagi, Mariko ; Kizaki, Zenro ; Bessho, Kazuhiko ; Kodama, Takahiro ; Iijima, Kazumoto ; Yorifuji, Tohru ; Matsuzaki, Yasushi ; Honda, Akira. / Serum amino acid profiling in citrin-deficient children exhibiting normal liver function during the apparently healthy period. JIMD Reports. Springer, 2019. pp. 53-61 (JIMD Reports).
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author = "Teruo Miyazaki and Hironori Nagasaka and Haruki Komatsu and Ayano Inui and Ichiro Morioka and Hirokazu Tsukahara and Shunsaku Kaji and Satoshi Hirayama and Takashi Miida and Hiroki Kondou and Kenji Ihara and Mariko Yagi and Zenro Kizaki and Kazuhiko Bessho and Takahiro Kodama and Kazumoto Iijima and Tohru Yorifuji and Yasushi Matsuzaki and Akira Honda",
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AU - Komatsu, Haruki

AU - Inui, Ayano

AU - Morioka, Ichiro

AU - Tsukahara, Hirokazu

AU - Kaji, Shunsaku

AU - Hirayama, Satoshi

AU - Miida, Takashi

AU - Kondou, Hiroki

AU - Ihara, Kenji

AU - Yagi, Mariko

AU - Kizaki, Zenro

AU - Bessho, Kazuhiko

AU - Kodama, Takahiro

AU - Iijima, Kazumoto

AU - Yorifuji, Tohru

AU - Matsuzaki, Yasushi

AU - Honda, Akira

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N2 - 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.

AB - 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.

KW - Age-matched control study

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KW - Gluconeogenesis

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