Haas D, Gan-Schreier H, Langhans CD, Rohrer T, Engelmann G, Heverin M, Russell DW, Clayton PT, Hoffmann GF, Okun JG. Differential diagnosis in patients with suspected bile acid synthesis defects. World J Gastroenterol 2012; 18(10): 1067-1076 [PMID: 22416181 DOI: 10.3748/wjg.v18.i10.1067]
Corresponding Author of This Article
Dr. Dorothea Haas, Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children´s Hospital, Im Neuenheimer Feld 430, Heidelberg D-69120, Germany. dorothea.haas@med.uni-heidelberg.de
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World J Gastroenterol. Mar 14, 2012; 18(10): 1067-1076 Published online Mar 14, 2012. doi: 10.3748/wjg.v18.i10.1067
Differential diagnosis in patients with suspected bile acid synthesis defects
Dorothea Haas, Hongying Gan-Schreier, Claus-Dieter Langhans, Tilman Rohrer, Guido Engelmann, Maura Heverin, David W Russell, Peter T Clayton, Georg F Hoffmann, Jürgen G Okun
Dorothea Haas, Hongying Gan-Schreier, Claus-Dieter Langhans, Georg F Hoffmann, Jürgen G Okun, Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children´s Hospital, Heidelberg D-69120, Germany
Tilman Rohrer, Department of Pediatric Endocrinology and Diabetology, University Hospital Saarland, Homburg D-66421, Germany
Guido Engelmann, Department of General Pediatrics, Gastroenterology, University Children’s Hospital, Heidelberg D-69120, Germany
Maura Heverin, Karolinska Institute, Karolinska University Hospital Huddinge, Huddinge 14186, Sweden
David W Russell, Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390-9046, United States
Peter T Clayton, Clinical and Molecular Genetics Unit, Institute of Child Health, London WC1N 1EH, United Kingdom
Author contributions: Haas D participated in the design of the study, was involved in the clinical evaluation of patients and drafted the manuscript; Gan-Schreier H and Langhans CD established the ESI-MS/MS method; Rohrer T and Engelmann G were involved in the clinical evaluation of patients; Heverin M determined 3β-hydroxy-Δ5-C27-steroid-dehydrogenase activity in fibroblasts; Russell DW carried out the molecular genetic studies; Clayton PT provided samples of patients affected with known disorders of bile acid metabolism; Hoffmann GF made substantial contributions to conception and interpretation of the study; Okun JG conceived of the study, participated in its design and coordination and helped to draft the manuscript.
Supported by Grants from the United States National Institutes of Health (GM069338 and HL20948) awarded to Russell DW
Correspondence to: Dr. Dorothea Haas, Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children´s Hospital, Im Neuenheimer Feld 430, Heidelberg D-69120, Germany. dorothea.haas@med.uni-heidelberg.de
Telephone: +49-6221-5639330 Fax: +49-6221-565565
Received: May 3, 2011 Revised: November 17, 2011 Accepted: December 10, 2011 Published online: March 14, 2012
Abstract
AIM: To investigate the clinical presentations associated with bile acid synthesis defects and to describe identification of individual disorders and diagnostic pitfalls.
METHODS: Authors describe semiquantitative determination of 16 urinary bile acid metabolites by electrospray ionization-tandem mass spectrometry. Sample preparation was performed by solid-phase extraction. The total analysis time was 2 min per sample. Authors determined bile acid metabolites in 363 patients with suspected defects in bile acid metabolism.
RESULTS: Abnormal bile acid metabolites were found in 36 patients. Two patients had bile acid synthesis defects but presented with atypical presentations. In 2 other patients who were later shown to be affected by biliary atresia and cystic fibrosis the profile of bile acid metabolites was initially suggestive of a bile acid synthesis defect. Three adult patients suffered from cerebrotendinous xanthomatosis. Nineteen patients had peroxisomal disorders, and 10 patients had cholestatic hepatopathy of other cause.
CONCLUSION: Screening for urinary cholanoids should be done in every infant with cholestatic hepatopathy as well as in children with progressive neurological disease to provide specific therapy.
