citrin蛋白缺陷导致的肝内胆汁淤积症10例临床观察

目的总结citrin蛋白缺陷导致的肝内胆汁淤积症患儿的临床表现和实验室检查的特点。方法对10例肝内胆汁淤积和黄疸患儿进行常规实验室检查,结合血串联质谱分析及基因检查诊断为新生儿肝内胆汁淤积症（NICCD）。对确诊患儿的临床表现、常规实验室检查、血氨基酸谱和酰基肉碱谱等进行分析。结果 NICCD患儿黄疸出现较早,迁延不退并加重,食纳下降,生长发育迟缓。实验室改变包括γ-谷氨酰转移酶、碱性磷酸酶以及甲胎蛋白升高,高胆红素血症,低蛋白血症,凝血酶原时间延长,明显低血糖,均有轻度高氨血症。肝活检病理提示大部分肝细胞呈空泡样变性,肝细胞内胆汁淤积,胆管区胆小管扩张。串联质谱分析发现多数患儿有特异性瓜氨酸、蛋氨酸、苏氨酸和酪氨酸升高,以及游离肉碱、C2、C3和长链酰基肉碱升高。结论不明原因黄疸患儿鉴别诊断应考虑到NICCD,早期进行串联质谱分析对明确NICCD的诊断及预后具有重要意义。

Clinical observation of 10 patients with intrahepatic cholestasis caused by citrin protein deficiency

Objective To summarize the clinical manifestations and laboratory characteristics of the children with in- trahepatic cholestasis caused by citrin protein deficiency. Methods Ten children with intrahepatic cholestasis and jaundice were given routine laboratory tests and the disease was diagnosed as neonatal intrahepatic cholestasis caused by Citrin deficiency（NICCD） combining the blood tandem mass spectrometry analysis and the genetic examination. The children＇s clinical manifestations, routine laboratory tests, blood amino acid profile and acyl-carnitine spectrum were analyzed. Results For children with NICCD, jaundice appeared earlier, delayed and aggravated, appetite decreased, and growth and development slowed. Laboratory changes included γ-glutamyl transferase, alkaline phosphatase and al- pha-fetoprotein elevation, hyperbilirubinemia, hypoalbuminemia and prolonged prothrombin time. All the children had significant hypoglycemia and mild hyperammonemia. Liver biopsy suggested vacuolar degeneration of most liver cells, cholestasis in liver cells and cholangiole dilatation in the bile duct area. Tandem mass spectrometry analysis showed that the majority of children had significantly increased specific citrulline, methionine, threonine and tyrosine and ele- vated free carnitine, C2, C3 and long-chain acylcarnitine. Conclusion For children with unexplained jaundice, the differential diagnosis should consider NICCD. The early tandem mass spectrometry analysis has important significance to confirming the diagnosis and prognosis of NICCD.