title: Treatment of bile acid amidation defects with glycocholic acid.
abstract: Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated five patients (one male, four females) from four families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form, of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and posttreatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction, and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1,000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients.
  
  
  CONCLUSIONS
  Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH; Clinical and Translational Research Center, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.
authors.forename: James E
authors.initials: JE
authors.lastname: Heubi
authors.forename: Kenneth D R
authors.initials: KD
authors.lastname: Setchell
authors.forename: Pinky
authors.initials: P
authors.lastname: Jha
authors.forename: Donna
authors.initials: D
authors.lastname: Buckley
authors.forename: Wujuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenthal
authors.forename: Carol
authors.initials: C
authors.lastname: Potter
authors.forename: Simon
authors.initials: S
authors.lastname: Horslen
authors.forename: David
authors.initials: D
authors.lastname: Suskind
mesh_terms: D000217:Acyltransferases / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D001647:Bile Acids and Salts / Q000378:metabolism; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004872:Ergocalciferols / Q000097:blood; D005260:Female; D006000:Glycocholic Acid / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy*; D024505:Tocopherols / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D004872:Ergocalciferols; D000217:Acyltransferases; C026953:bile acid-CoA amino acid N-acyltransferase; D006000:Glycocholic Acid; D024505:Tocopherols