Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2018

AUTHORS

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

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. More... »

PAGES

1-9

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/8904_2018_99

    DOI

    http://dx.doi.org/10.1007/8904_2018_99

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1103258251

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29654547


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