Shigetomi Hiroko, Tanaka Toju, Nagao Masayoshi, Tsutsumi Hiroyuki
Department of Pediatrics and Clinical Research, National Hospital Organization Hokkaido Medical Center, 5-7 Yamanote, Nishi-ku, Sapporo 063-0005, Japan.
Department of Pediatrics, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo 060-8543, Japan.
Int J Neonatal Screen. 2018 Jan 16;4(1):5. doi: 10.3390/ijns4010005. eCollection 2018 Mar.
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.
瓜氨酸血症是由于瓜氨酸缺乏导致的新生儿肝内胆汁淤积症（NICCD）中最早可识别的生化异常，并且它已被纳入使用串联质谱法的新生儿筛查项目中。然而，在2006年至2017年期间，日本北海道札幌市出生的60万名婴儿中只有一名新生儿呈阳性。我们调查了12名最初在新生儿质谱筛查（NBS）中被认为正常，但后来通过DNA检测被诊断为NICCD的新生儿。利用他们最初的NBS数据，我们检查了瓜氨酸浓度以及瓜氨酸与总氨基酸的比率。尽管他们的瓜氨酸值超过了正常新生儿的平均值，并且其中80%超过了+3个标准差（SD），但所有值均低于40 nmol/mL的临界值。与对照组相比，NICCD患者中瓜氨酸与总氨基酸的比率显著升高。通过同时评估两个指标，我们可以筛选出约80%漏诊的NICCD患者。引入一个包含瓜氨酸值和瓜氨酸与总氨基酸比率的估计指数可以确保通过NBS检测出NICCD。
