Translational Medicine Practice And Follow-up Of Infantile Cholestatic Hepatopathy

Objective:This study used tandem mass spectrometry and gene test to combine the clinics and practice translational medicine in children with cholestatic liver disease.Methods:26 infants with cholestatic liver disease admitted to the Department of Pediatrics,First Affiliated Hospital of Kunming Medical University were enrolled as subjects from July 2012 to January 2019.The clinical data and tandem mass spectrometry and gene test results from them were collected,and the clinical prognosis of infants with Citrin deficiency induced infantile intrahepatic cholestasis were focused on and had telephone follow-up after discharging from the hospital.Results:1.16 of 26 cases were detected by tandem mass spectrometry,4 cases were found to be abnormal,12 cases had elevated amino acid and/or carnitine,and 8 of 12 cases were elevated citrulline.2.21 of 26 cases were genetically tested,12 of which had suspicious mutated genes associated with clinical phenotype,and were highly consistent with clinical(57%).3 of 12 cases were caused Citrin protein deficiency by SLC25A13 gene mutation.3 of 12 cases were caused Alagille syndrome type 1 by JAG1 gene mutation,2 were caused Alagille syndrome type 2 by NOTCH2 gene mutation,1 case was caused cystic fibrosis by CFTR gene mutation,and 1 case was caused hereditary hyperbilirubinemia by UGT1A1 gene mutation,1 case was caused progressive familial intrahepatic cholestasis by ABCB4 gene mutation,1 case was considered benign recurrent intrahepatic cholestasis type 2 by ABCB11 gene mutation.9 of 21cases did not find a mutated gene associated with the clinical phenotype(43%).3.8 infants with NICCD developed yellow staining after birth,and delayed yellow dyeing,with increased liver enzyme index,cholestasis,high GGT,high citrullineemia,high lactateemia,and stool color lightening,liver enlargement,hypoglycemia and hyperammonemia in some cases.4.8 children with NICCD were followed up successfully,and all of them were improved after feeding lactose-free milk powder.There were no cases with adult citrullin type Ⅱ neuropsychiatric symptoms,liver failure,liver transplantation and death caused by Citrin deficiency.In 8 cases,the yellow staining completely subsided,the liver function was normal,and the blood lipids were normal.Some of 8 cases like the food which was rich in high protein and fat.Some dislike carbohydrates and had growth retardation.Conclusions:The concept of translational medicine can guide clinical practice.The problems found in diagnosing and treating infantile cholestatic liver disease can be feedbacked to the laboratory,and from laboratory to clinical application again,which helps to clarify the cause,guide diagnosis and treatment and improve prognosis.Early diagnosis of NICCD,reasonable dietary intervention and follow-up can help improve prognosis.