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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 Report
Part of the JIMD Reports book series

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.

Keywords

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

Notes

Acknowledgement

Details of the contributions of individual authors as (a) conception and design, (b) data analysis, (c) data interpretation, (d) drafting the article, (e) revising the article, and (f) clinical diagnosis/treatment and sample collection: Miyazaki T: (a, b, c, d); Nagasaka H: (a, b, c, d, f); Komatsu H: (c, f); Inui A: (c, f); Morioka I: (c, f); Tsukahara H: (c, f); SKaji S: (c, f); Hirayama S: (c, f); Miida T: (c, f); Kondou H: (c, f); Ihara K: (c, f); Yagi M: (c, f); Kizaki Z: (c, f); Bessho K: (c, f); Kodama T: (c, f); Iijima K: (c, f); Yorifuji T: (c, f); Matsuzaki Y: (e); and Honda A: (a, b, c, e).

Supplementary material

8904_2018_99_MOESM1_ESM.zip (342 kb)
Supplementary Fig. S1 (ZIP 342 kb)
8904_2018_99_MOESM2_ESM.pdf (76 kb)
Supplementary Table S1 (PDF 76 kb)
8904_2018_99_MOESM3_ESM.pdf (107 kb)
Supplementary Method 1 (PDF 107 kb)

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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Teruo Miyazaki
    • 1
  • Hironori Nagasaka
    • 2
  • Haruki Komatsu
    • 3
  • Ayano Inui
    • 4
  • Ichiro Morioka
    • 5
  • Hirokazu Tsukahara
    • 6
  • Shunsaku Kaji
    • 7
  • Satoshi Hirayama
    • 8
  • Takashi Miida
    • 8
  • Hiroki Kondou
    • 9
  • Kenji Ihara
    • 10
    • 11
  • Mariko Yagi
    • 12
  • Zenro Kizaki
    • 13
  • Kazuhiko Bessho
    • 14
  • Takahiro Kodama
    • 15
  • Kazumoto Iijima
    • 5
  • Tohru Yorifuji
    • 16
  • Yasushi Matsuzaki
    • 1
  • Akira Honda
    • 1
  1. 1.Division of Gastroenterology, Joint Research CenterTokyo Medical University Ibaraki Medical CenterAmiJapan
  2. 2.Department of PediatricsTakarazuka City HospitalTakarazukaJapan
  3. 3.Department of PediatricsToho University Sakura Medical CenterChibaJapan
  4. 4.Department of Pediatric Hepatology and GastroenterologySaiseikai Yokohamashi Tobu HospitalYokohamaJapan
  5. 5.Department of PediatricsKobe University Graduate School of MedicineKobeJapan
  6. 6.Department of PediatricsOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  7. 7.Department of PediatricsTsuyama-Chuo HospitalTsuyama, OkayamaJapan
  8. 8.Department of Clinical Laboratory MedicineJuntendo University School of MedicineTokyoJapan
  9. 9.Department of PediatricsKindai University Nara HospitalNaraJapan
  10. 10.Department of PediatricsKyushu University Graduate School of Medical ScienceFukuokaJapan
  11. 11.Department of Pediatrics, Faculty of MedicineOita UniversityYufu, OitaJapan
  12. 12.Department of PediatricsNikoniko House Medical and Welfare CenterKobeJapan
  13. 13.Department of PediatricsJapanese Red Cross Kyoto Daiichi HospitalKyotoJapan
  14. 14.Department of PediatricsGraduate School of Medicine, Osaka UniversityOsakaJapan
  15. 15.Department of Gastroenterology and HepatologyGraduate School of Medicine, Osaka UniversityOsakaJapan
  16. 16.Division of Pediatric Endocrinology and MetabolismChildren’s Medical Center, Osaka City General HospitalOsakaJapan

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