6例citrin缺陷导致新生儿肝内胆汁淤积症的临床特点及基因分析

摘要

Objective To investigate the clinical characteristics and SLC25 A13 genetic features of neonatal intrahe-patic cholestasis caused by citrin deficiency ( NICCD) . Methods Thirty-two children with idiopathic cholestasis were screened for the SLC25A13 mutations by PCR. The biochemical index was detected and the blood amino acids was ana-lyzed by tandem mass spectrometry. Results Six cases were diagnosed as NICCD, of which two cases were homozygous 851del4 mutation ([Ⅰ]/[Ⅰ] ) and the other four cases were compound heterozygous mutations. Five cases were neo-natal onset and only one case was infantile onset. The serum ALT was slightly increased and serum AST was higher than ALT. All patients were hypoalbuminemia less than 35 g/L and obvious hypoglycaemia, but none was symptomatic. All of them had aminoacidemia. The most commonly increased amino acids were citrulline and tyrosine. Conclusion NIC-CD is an important cause of infants with idiopathic cholestasis. Genetic analysis of SLC25A13 may be helpful in the ear-ly detection of NICCD.%目的：分析citrin缺陷导致新生儿肝内胆汁淤积症( neonatal intrahepatic cholestasis caused by citrin deficiency,NICCD)的临床特点及SLC25A13基因突变。方法应用PCR扩增和测序,对南京医科大学附属南京儿童医院收治的32例特发性胆汁淤积症患儿进行SLC25A13基因突变分析、生化指标检测及串联质谱法分析血氨基酸。结果6例患儿诊断为NICCD,其中2例患儿为纯合突变851del4突变([Ⅰ]/[Ⅰ]),其他4例患儿为复合杂合突变；5例患儿为新生儿期发病,1例患儿为婴儿期发病；患儿血清谷丙转氨酶( ALT)水平轻度升高,谷草转氨酶( AST)高于ALT；患儿均出现白蛋白<35 g/L和显著低血糖,但均无临床症状；患儿均出现高氨基酸血症,最常见的血氨基酸升高为瓜氨酸和酪氨酸。结论 NICCD是我国小儿特发性胆汁淤积症的一种重要原因。SLC25A13基因突变分析有助于NICCD的早期诊断。