Clinical characteristics and genetic analysis of neonatal intrahepatic cholestasis caused by citrin deficiency in comparison with idiopathic neonatal cholestasis.

To compare the clinical and genetic characteristics of patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and idiopathic neonatal cholestasis (INC). The clinical data of 30 patients with NICCD and 30 patients with INC admitted in Children's Hospital of Chongqing Medical University during September 2012 and December 2017 were retrospectively analyzed. The clinical manifestations, biochemical indicators and genetic characteristics were compared between two groups. Patients in both groups presented similar clinical manifestations, however the chubby face and clay-colored stool were more common in NICCD patients (both <0.01). Comparing with INC group, NICCD group showed significantly decreased blood levels of glucose, prealbumin, albumin, total protein, fibrinogen, and aminotransferases (<0.05 or <0.01), while significantly increased blood levels of indirect bilirubin, total bile acid, alkaline phosphatase, lactic dehydrogenase, ammonium, alpha fetoprotein, and markers of coagulation function (<0.05 or <0.01). In addition, NICCD patients showed remarkably increased blood levels of citrulline, methionine, tyrosine, arginine, and threonine; as well as significantly increased urine levels of 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvic acid and phenyllactic acid, while those indicators in INC patients were normal (all <0.01). All the patients with NICCD had mutation including 8 homozygotes, 9 compound heterozygotes, and 13 single heterozygotes. Among all mutations, c.851_854del was most common (53.19%), c.1196T>A and c.919G>T were two novel mutations. The manifestations of chubby face and clay-colored stool may provide clue for early diagnosis of NICCD along with the elevated biochemical parameters, such as ammonium, alpha-fetal protein, citrulline in blood and 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvic acid, phenyllactic acid in urine. Target gene trapping and high-throughput sequencing have the key values in diagnosis and differential diagnosis of NICCD.