Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, P.R. China.
J Pediatr Endocrinol Metab. 2023 Nov 10;36(12):1154-1160. doi: 10.1515/jpem-2023-0026. Print 2023 Dec 15.
To find biochemical and molecular markers can assist in identifying serious liver damage of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) patients.
138 patients under 13 days to 1.1 year old diagnosed of NICCD in our center from 2004 to 2020. Base on the abnormal liver laboratory tests, we divided 138 patients into three groups: acute liver failure (ALF), liver dysfunction, and non-liver dysfunction groups, then compared their clinical, biochemical and, molecular data.
96 % of 138 patients had high levels of citrulline and high ratio of threonine to serine, which is the distinctive feature of plasma amino acid profile for NICCD. A total of 18.1 % of 138 patients had evidence of ALF who presented the most severity hepatic damage, 51.5 % had liver dysfunction, and the remaining 30.4 % presented mild clinical symptoms (non-liver dysfunction). In ALF group, the levels of citrulline, tyrosine, TBIL, ALP, and γ-GT was significantly elevated, and the level of ALB and Fisher ratio was pronounced low. Homozygous mutations of 1,638_1660dup, IVS6+5G.A, or IVS16ins3kb in gene were only found in ALF and liver dysfunction groups. Supportive treatment including medium-chain triglyceride supplemented diet and fresh frozen plasma could be life-saving and might reverse ALF.
High level of citrulline, tyrosine, TBIL, ALP, γ-GT, and ammonia, low level of albumin, and low Fisher ratio were predictors to suggest severe liver damage in NICCD patients who may go on to develop fatal metabolic disorder. Early identification and proper therapy is particularly important for these patients.
寻找生化和分子标志物，以协助识别由于 citrin 缺乏引起的新生儿肝内胆汁淤积症（NICCD）患者的严重肝损伤。
收集 2004 年至 2020 年在本中心诊断为 NICCD 的 138 例 13 天至 1.1 岁的患者。根据异常的肝脏实验室检查，我们将 138 例患者分为三组：急性肝衰竭（ALF）、肝功能障碍和非肝功能障碍组，然后比较三组的临床、生化和分子数据。
138 例患者中有 96%的患者精氨酸水平升高，苏氨酸/丝氨酸比值升高，这是 NICCD 患者血浆氨基酸谱的特征。138 例患者中共有 18.1%有 ALF 的证据，表现出最严重的肝损伤，51.5%有肝功能障碍，其余 30.4%表现出轻度临床症状（非肝功能障碍）。在 ALF 组，精氨酸、酪氨酸、总胆红素、碱性磷酸酶和 γ-谷氨酰转移酶水平显著升高，白蛋白和 Fisher 比值明显降低。基因 1,638_1660dup、IVS6+5G.A 或 IVS16ins3kb 的纯合突变仅在 ALF 和肝功能障碍组中发现。中链甘油三酯补充饮食和新鲜冷冻血浆等支持性治疗可能是救命的，并可能逆转 ALF。
高水平的精氨酸、酪氨酸、总胆红素、碱性磷酸酶、γ-谷氨酰转移酶和氨，低水平的白蛋白和低的 Fisher 比值是提示 NICCD 患者严重肝损伤的预测指标，这些患者可能会发展为致命的代谢紊乱。早期识别和适当的治疗对这些患者尤为重要。
