Abstract: Objective To investigate the clinical characteristics and gene mutation of children with Citrin defect.Methods The data including medical history,laboratory examination,gene mutations and treatment of 6 children with Citrin deficiency diagnosed in Xiamen Children's Hospital were retrospectively analyzed.Results Among the six cases,5 of them were admitted to hospital due to cholestasis and delayed development.The age of the cases ranged from 1m7d to 4m.Biochemical results showed that total bilirubin (141.3～231.3 μmol/L) and conjugated bilirubin (41.5～94.9 μmol/L) were increased,AST(49～148 U/L)＞ALT(10～41 U/L),hypoglycemia(2.31～3.5 mmol/L),hypoproteinemia(39.7～60.4 g/L),blood coagulation abnormality(PT 11.2～23.5s). The alpha fetoprotein were significantly increased(＞3 000～15 000 ng/mL),and blood tandem mass spectrometry showed that hyper citrullinemia.Urine mass spectrometry showed that 4-hydroxyphenyllactate,4-hydroxyphenylpropionic acid and 4-hydroxyphenylacetic acid were increased.Five children were treated with lactose free fortified medium chain fatty acid milk powder,ursodeoxycholic acid and fat soluble vitamins for 1-2 months,and jaundice subsided.One child was hospitalized because of the increase of total bile acid for more than 7 years,and had hypoglycemic syncope twice in the morning.Children have special dietary preferences,like high protein and high fat food.Six cases of children underwent full exome gene detection,and analysis revealed five of them with SLC25A13 gene mutations.C.852-855del was a common mutation.In case 6,the SLC25A13 gene mutation and the SLC10A1 gene mutation were detected,and the final diagnosis was Citrin deficiency and NTCP gene deficiency.The child is undergoing dietary treatment and follow-up.Conclusion The clinical manifestations of Citrin deficiency are diverse.In addition to cholestasis in the neonatal period,children with unexplained hypoglycemic syncope and a special diet preference to protein-rich foods should also be alert to Citrin deficiency.Early improvement of hematuria tandem mass spectrometry and genetic testing can help to confirm the diagnosis.Early and accurate management of patients can effectively improve the prognosis of patients.

Key words: Citrin deficiency, Clinical characteristics, genotype