Lee Ni-Chung, Chien Yin-Hsiu, Kobayashi Keiko, Saheki Takeyori, Chen Huey-Ling, Chiu Pao-Chin, Ni Yen-Hsuan, Chang Mei-Hwei, Hwu Wuh-Liang
Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
J Inherit Metab Dis. 2006 Aug;29(4):551-5. doi: 10.1007/s10545-006-0250-y. Epub 2006 May 30.
Citrin is a mitochondrial membrane aspartate-glutamate carrier, and citrin deficiency causes both hyperammonaemia in adults (adult-onset type II citrullinaemia, CTLN2) and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), with metabolic derangements in gluconeogenesis, aerobic glycolysis, urea synthesis, UDP-galactose epimerase activity, and possibly fatty acid synthesis and utilization. Through neonatal screening and case review, four patients with NICCD who had an acylcarnitine profile during infancy were all found to have an elevation of free carnitine, C2-carnitine, and long-chain acylcarnitines. These metabolic abnormalities appeared after the rise of citrulline and bilirubin, but before the elevation of alanine aminotransferase and aspartate aminotransferase. Although the rise of free carnitine and acylcarnitines seems to be a benign condition, the sequential changes of these metabolic derangements may give clues to the pathogenesis of this interesting disorder.
Citrin是一种线粒体膜天冬氨酸-谷氨酸载体，Citrin缺乏会导致成人高氨血症（成人发作型II型瓜氨酸血症，CTLN2）以及由Citrin缺乏引起的新生儿肝内胆汁淤积症（NICCD），同时在糖异生、有氧糖酵解、尿素合成、UDP-半乳糖表异构酶活性以及可能的脂肪酸合成和利用方面出现代谢紊乱。通过新生儿筛查和病例回顾，发现4例在婴儿期进行过酰基肉碱谱分析的NICCD患者的游离肉碱、C2-肉碱和长链酰基肉碱均升高。这些代谢异常在瓜氨酸和胆红素升高之后出现，但在丙氨酸转氨酶和天冬氨酸转氨酶升高之前出现。尽管游离肉碱和酰基肉碱的升高似乎是一种良性情况，但这些代谢紊乱的相继变化可能为这种有趣疾病的发病机制提供线索。
