Bile acid metabolism in extrahepatic biliary atresia: lithocholic acid in stored dried blood collected at neonatal screening.
Lithocholic acid (LCA) is a potent hepatotoxic compound. Fetal LCA may have a role in the pathogenesis of neonatal cholestasis/extrahepatic biliary atresia (EHBA). Fetal liver efficiently hydroxylates LCA in several positions. This may represent a detox-ification mechanism. In the present study LCA, cholic acid (CA) and chenodeoxycholic acid (CDCA) were quantitated by gas chromatography-mass spectrometry using selected ion monitoring in small amounts of stored dried blood from six newborn infants with EHBA and fourteen con-trols. The blood was collected at neonatal metabolic screening. Mean blood levels (+/- S.E.M.) of LCA were 0.11 +/- 0.04 microM in the in-fants with EHBA and 0.08 +/- 0.02 microM in the control infants. The correspon-ding levels for CA and CDCA were 15.6 +/- 3.6 microM and 7.4 +/- 2.5 microM in the infants with EHBA and 1.7 +/- 0.3 microM and 1.8 +/- 0.4 microM in the controls. The increased levels of CA and CDCA in the infants with liver disease can be explained by cholestasis. The low blood levels of LCA indicate a normal fetal metabolism of this bile acid in EHBA.
Department of Women's and Children's Health, Uppsala University, Sweden.
Jan
J
Gustafsson
Gunvor
G
Alvelius
Ingemar
I
Björkhem
Antal
A
Nemeth
D001656:Biliary Atresia / Q000175:diagnosis* / Q000378:metabolism; D001800:Blood Specimen Collection; D002635:Chenodeoxycholic Acid / Q000097:blood / Q000378:metabolism; D019826:Cholic Acid / Q000097:blood / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007231:Infant, Newborn; D008095:Lithocholic Acid / Q000097:blood* / Q000378:metabolism; D008297:Male; D015997:Neonatal Screening
D002635:Chenodeoxycholic Acid; D008095:Lithocholic Acid; D019826:Cholic Acid