title: The Features of GGT in Patients with ATP8B1 or ABCB11 Deficiency Improve the Diagnostic Efficiency.
abstract: OBJECTIVE
  Genetic defects in ATP8B1 or ABCB11 account for the majority of cholestasis with low GGT. But the ranges for GGT in patients with ATP8B1 or ABCB11 deficiency are unclear. This study tried to unravel the features of GGT in these patients that improve diagnostic efficiency.
  
  
  METHODS
  This study enrolled 207 patients with chronic cholestasis who were ordered to test for ATP8B1 and/or ABCB11 from January 2012 to December 2015. Additional 17 patients with ATPB81 or ABCB11 deficiency diagnosed between January 2004 and December 2011 were also enrolled in this study. 600 population-matched children served as controls. Clinical data were obtained by retrospectively reviewing medical records.
  
  
  RESULTS
  A total of 26 patients were diagnosed with ATP8B1 deficiency and 30 patients were diagnosed with ABCB11 deficiency. GGT levels were similar between the two disorders at any observed month of age, but varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year. GGT levels in patients with a genetic diagnosis were different from that in patients without a genetic diagnosis and controls. Larger ranges for GGT were found in patients without a genetic diagnosis. Some controls had GGT≥70U/L in the 2nd~6th month. Of the 207 patients, 39 (18.8%) obtained a genetic diagnosis. 111 patients met the ranges described above, including all the 39 patients with ATP8B1 or ABCB11 deficiency. The sensitivity was 100.0%. The rate of a positive molecular diagnosis increased to 35.1% (39/111 vs. 39/207, X2 = 10.363, P = 0.001). The remaining 96 patients exceeded the ranges described above and failed to receive a genetic diagnosis. These patients accounted for 43.8% of sequencing cost.
  
  
  CONCLUSIONS
  GGT levels in patients with ATP8B1 or ABCB11 deficiency varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year.
authors.affiliation: Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, China.
authors.forename: Neng-Li
authors.initials: NL
authors.lastname: Wang
authors.affiliation: The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Li
authors.affiliation: The Molecular Genetic Diagnosis Center, Shanghai Key Lab of Birth Defects, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Gong
authors.affiliation: The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Kuerbanjiang
authors.initials: K
authors.lastname: Abuduxikuer
authors.affiliation: The Molecular Genetic Diagnosis Center, Shanghai Key Lab of Birth Defects, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, China.|The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Jian-She
authors.initials: JS
authors.lastname: Wang
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002779:Cholestasis / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D005723:gamma-Glutamyltransferase / Q000235:genetics*
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D005723:gamma-Glutamyltransferase; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human