Effects of citrin deficiency in the perinatal period: Feasibility of newborn mass screening for citrin deficiency
Effects of citrin deficiency in the perinatal period: Feasibility of newborn mass screening for citrin deficiency
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DOI：
10.1203/01.pdr.0000139713.64264.bc
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发表时间：
2004-10-01
影响因子：
3.6
通讯作者：
Yamano, T
中科院分区：
文献类型：
--
作者：
Tamamori, A;Fujimoto, A;Yamano, T
由于SLC25A13基因突变导致的Citrin缺陷会导致成人型II型瓜氨酸血症(CTLN2)和一种类型的新生儿肝内胆汁淤积症(NICCD)。大约一半的NICCD患者是在新生儿大规模筛查(NMS)中发现高半乳糖、苯丙氨酸和/或蛋氨酸浓度的。为明确NMS对围产儿和新生儿的影响及不一致的结果，我们检测了20例NICCD患者NMS的血氨、胆汁酸和半乳糖水平。出生体重对胎龄的影响较低(-1.4+/-0.7 SD)。受影响的胎儿可能患有宫内胆红素缺乏症。出生后发现的第一个异常是瓜氨酸血症，20例患者中有19例瓜氨酸水平高于对照组+2 SD。在出生后第5天，酪氨酸、苯丙氨酸、蛋氨酸、半乳糖和胆汁酸受到的影响小于瓜氨酸。半乳糖和胆汁酸水平在出生后1个月较第5天升高，这是由于肝细胞线粒体胞浆NADH还原当量供应受损所致。NMS阴性的患者血清总20种氨基酸水平较低。所有患者的瓜氨酸/丝氨酸、瓜氨酸/亮氨酸+异亮氨酸、瓜氨酸/总氨基酸比值(控制低总氨基酸的混杂效应)分别高于对照组的+2 SD、+2 SD和+3 SD。Citrin缺乏症的NMS(东亚地区SLC25A13突变纯合子频率：1/10,000-1/38,000)将有助于阐明这种疾病的临床病程、治疗和预防。
Deficiency of citrin due to mutations of the SLC25A13 gene causes adult-onset type II citrullinemia (CTLN2) and one type of neonatal intrahepatic cholestasis (NICCD). About half of the NICCD patients are detected based on high galactose, phenylalanine, and/or methionine concentrations on newborn mass screening (NMS). To clarify the perinatal and neonatal effects and the inconsistent results on NMS, we examined aminograms, the levels of bile acids and galactose in dried blood spots for NMS from 20 patients with NICCD. Birth weight was low for gestational age (-1.4 +/- 0.7 SD). Affected fetuses may have suffered intrauterine citrin deficiency. The first abnormality detected after birth was citrullinemia, and 19 of 20 patients had citrulline levels higher than +2 SD of controls. Tyrosine, phenylalanine, methionine, galactose, and bile acids were less affected than citrulline on d 5 after birth. Galactose and bile acids levels were increased at 1 mo in comparison with d 5 after birth due to impairment of the cytosolic NADH reducing-equivalent supply into mitochondria of hepatocytes. Patients with negative findings on NMS had low levels of total 20 amino acids. Citrulline/serine, citrulline/leucine plus isoleucine, and citrulline/total amino acids ratios, controlled for the confounding effect of low amount of total amino acids, were higher in all patients than +2 SD, +2 SD, and +3 SD of controls, respectively. NMS for citrin deficiency (frequency of homozygote with SLC25A13 mutation: 1/10,000-1/38,000 in East Asia) will be useful for clarification of the clinical course, treatment, and prevention of this disease.