Tamamori Akiko, Okano Yoshiyuki, Ozaki Hajime, Fujimoto Akie, Kajiwara Masue, Fukuda Kazuyoshi, Kobayashi Keiko, Saheki Takeyori, Tagami Yasuko, Yamano Tsunekazu
Department of Paediatrics, Fujiidera City Hospital, Fujiidera, Japan.
Eur J Pediatr. 2002 Nov;161(11):609-13. doi: 10.1007/s00431-002-1045-2. Epub 2002 Sep 10.
Adult-onset type 2 citrullinaemia (CTLN2) is caused by a deficiency of the citrin protein encoded by the SLC25A13 gene. Citrin, an aspartate glutamate carrier in mitochondria, is an essential component of the malate-aspartate NADH shuttle. Recently, citrin deficiency has been reported to manifest as neonatal intrahepatic cholestasis. We report here five cases with neonatal intrahepatic cholestasis caused by citrin deficiency. Genetic diagnosis revealed compound heterozygotes of 851del4/IVS11 + 1G-->A in two patients, IVS11 + 1G-->A/E601X, and IVS11 + 1G-->A/unknown in each one patient and homozygote for S225X in one patient. All cases revealed high levels of alpha-fetoprotein, which are not observed in CTLN2 patients. The condition was self-limiting and spontaneously disappeared after 5-7 months of age in four patients. However, one patient developed hepatic dysfunction from the age of 6 months and required a living-related liver transplantation at the age of 10 months. The patient showed complete recovery after transplantation, and now at the age of 3 years, shows normal growth and mental development.
we report the first case of neonatal intrahepatic cholestasis caused by citrin deficiency with severe hepatic dysfunction requiring a living-related liver transplantation. Patients with this disorder should be followed up carefully, even during infancy.
成人起病型2型瓜氨酸血症（CTLN2）由SLC25A13基因编码的citrin蛋白缺乏所致。Citrin是线粒体中的一种天冬氨酸谷氨酸载体，是苹果酸 - 天冬氨酸NADH穿梭系统的重要组成部分。最近，据报道citrin缺乏表现为新生儿肝内胆汁淤积。我们在此报告5例由citrin缺乏引起的新生儿肝内胆汁淤积病例。基因诊断显示，两名患者为851del4/IVS11 + 1G→A的复合杂合子，一名患者为IVS11 + 1G→A/E601X，一名患者为IVS11 + 1G→A/未知，一名患者为S225X纯合子。所有病例均显示甲胎蛋白水平升高，这在CTLN2患者中未观察到。病情呈自限性，4例患者在5至7个月龄后自发消失。然而，一名患者从6个月龄开始出现肝功能障碍，10个月龄时需要进行活体亲属肝移植。该患者移植后完全康复，现在3岁，生长和智力发育正常。
我们报告了首例由citrin缺乏引起的新生儿肝内胆汁淤积伴严重肝功能障碍并需要进行活体亲属肝移植的病例。即使在婴儿期，也应对患有这种疾病的患者进行仔细随访。
