title: [Studies on the clinical manifestation and SLC25A13 gene mutation of Chinese patients with neonatal intrahepatic cholestasis caused by citrin deficiency].
abstract: OBJECTIVE
  To investigate the clinical and laboratory features of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and to characterize the molecular basis and prognosis of this disease.
  
  
  METHODS
  Twenty-six patients with NICCD were collected because of idiopathic intrahepatic cholestasis and jaundice. The diagnosis was made by routine laboratory data collection, tandem mass spectrometry (MS-MS) and gas chromatography mass spectrometry (GC-MS) analyses. SLC25A13 gene mutation was analyzed by using polymerase chain reaction (PCR), direct DNA sequencing and restriction fragment length polymorphism analyses. The patients were followed up for nearly 2 years.
  
  
  RESULTS
  The NICCD patients showed low birth weight and the average onset of jaundice was 29 days. Laboratory data showed liver dysfunction, hyperbilirubinemia, hypoproteinemia, high levels of alpha-fetoprotein, prolonged prothrombin time, hypoglycemia and hyperammonemia. MS-MS analysis of the blood samples revealed specific elevation of citrulline, methionine, threonine, tyrosine and elevation of free carnitine, short-chain and long-chain acylcarnitines. GC-MS analysis of the urine samples showed elevated 4-hydroxyl phenyllactic acid and 4-hydroxyl phenylpyruvic acid. Twelve different mutations were identified, including 4 novel mutations, i.e., G386V, R467X, K453R and 1192-1193delT. Forty-four mutated alleles were identified in the 52 alleles (84.6% ). Among them, 851del4, 1638ins23 and IVS6+5G>A mutations were the most frequent mutations, accounting for 40.9%, 20.5% and 11.4% of the total alleles examined respectively. Five of the 26 patients have not been recovered, including 4 died and 1 accepted liver transplantation. No obvious relationship was found between the genotype and phenotype in NICCD.
  
  
  CONCLUSIONS
  The 851del4, 1638ins23 and IVS6+5G>A mutations are the hot-spot mutations in Chinese NICCD patients. Some NICCD patients have poor prognosis.
authors.affiliation: Department of Pediatric Endocrinology, Genetic and Metabolic Diseases, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Ya-zhi
authors.initials: YZ
authors.lastname: Xing
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Qiu
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Lian-shu
authors.initials: LS
authors.lastname: Han
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Xu
authors.forename: Hui-wen
authors.initials: HW
authors.lastname: Zhang
authors.forename: Xiao-lan
authors.initials: XL
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xue-fan
authors.initials: XF
authors.lastname: Gu
mesh_terms: D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D016022:Case-Control Studies; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics* / Q000628:therapy; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D027361:Organic Anion Transporters / Q000172:deficiency*; D011379:Prognosis
chemical_list: D002135:Calcium-Binding Proteins; D033681:Mitochondrial Membrane Transport Proteins; D027361:Organic Anion Transporters; C119629:SLC25A13 protein, human; C008822:citrin