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Int. J. Neonatal Screen. 2018, 4(1), 5; https://doi.org/10.3390/ijns4010005

Early Detection and Diagnosis of Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency Missed by Newborn Screening Using Tandem Mass Spectrometry

1
Department of Pediatrics and Clinical Research, National Hospital Organization Hokkaido Medical Center, 5-7 Yamanote, Nishi-ku, Sapporo 063-0005, Japan
2
Department of Pediatrics, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo 060-8543, Japan
*
Author to whom correspondence should be addressed.
Received: 12 December 2017 / Revised: 12 January 2018 / Accepted: 12 January 2018 / Published: 16 January 2018
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Abstract

Citrullinemia is the earliest identifiable biochemical abnormality in neonates with intrahepatic cholestasis due to a citrin deficiency (NICCD) and it has been included in newborn screening panels using tandem mass spectrometry. However, only one neonate was positive among 600,000 infants born in Sapporo city and Hokkaido, Japan between 2006 and 2017. We investigated 12 neonates with NICCD who were initially considered normal in newborn mass screening (NBS) by tandem mass spectrometry, but were later diagnosed with NICCD by DNA tests. Using their initial NBS data, we examined citrulline concentrations and ratios of citrulline to total amino acids. Although their citrulline values exceeded the mean of the normal neonates and 80% of them surpassed +3 SD (standard deviation), all were below the cutoff of 40 nmol/mL. The ratios of citrulline to total amino acids significantly elevated in patients with NICCD compared to the control. By evaluating two indicators simultaneously, we could select about 80% of patients with missed NICCD. Introducing an estimated index comprising citrulline values and citrulline to total amino acid ratios could assure NICCD detection by NBS. View Full-Text
Keywords: SLC25A13; amino acid ratio; citrullinemia; latent liver dysfunction; mitochondrial aspartate-glutamate carrier SLC25A13; amino acid ratio; citrullinemia; latent liver dysfunction; mitochondrial aspartate-glutamate carrier
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Shigetomi, H.; Tanaka, T.; Nagao, M.; Tsutsumi, H. Early Detection and Diagnosis of Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency Missed by Newborn Screening Using Tandem Mass Spectrometry. Int. J. Neonatal Screen. 2018, 4, 5.

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Int. J. Neonatal Screen. EISSN 2409-515X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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