Titration of bile acid supplements in 3beta-hydroxy-Delta 5-C27-steroid dehydrogenase/isomerase deficiency.
OBJECTIVE
3beta-Hydroxy-Delta 5-C27-steroid dehydrogenase/isomerase deficiency is a bile acid synthesis defect responsive to primary bile acids. We reviewed its clinical features and response to treatment with a mixture of ursodeoxycholic (UDCA) and chenodeoxycholic acid (CDCA) to titrate the dose of supplements required for disease control.


METHODS
We studied our patients by liquid chromatography-tandem mass spectrometry, liver function tests, and histology. After diagnosis all of the patients received a balanced mixture of UDCA/CDCA and the dose was titrated according to urinary levels of 3beta,7 alpha-dihydroxy-5-cholenoic acid (u-3beta-D-OH-5C).


RESULTS
Five patients presenting with giant cell hepatitis, biliary cirrhosis, and cryptogenic cirrhosis (1 each), and picked up by neonatal screening (2 patients) were diagnosed at a median age of 2.5 years (range 0.1-5.5). Normal levels of u-3beta-D-OH-5C were achieved after 4 months (range 3-28 months) from the start of the treatment. The minimum dose of UDCA/CDCA required to maintain normal u-3beta-D-OH-5C levels was 5/5 mg x kg(-1) x day(-1). A follow-up biopsy in 2 patients showed no progression of liver disease.


CONCLUSIONS
A mixture of UDCA/CDCA can effectively control 3beta-hydroxy-Delta 5-C27-steroid dehydrogenase/isomerase deficiency. Dose titration by liquid chromatography-tandem mass spectrometry warrants the maintenance of negative feedback on the abnormal synthetic pathway and avoids disease progression.
Riello
L
L
Department of Paediatrics, Paediatric Liver, University of Padova, Italy.
D'Antiga
L
L
Guido
M
M
Alaggio
R
R
Giordano
G
G
Zancan
L
L
D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency*; D001706:Biopsy; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002793:Cholic Acids / Q000652:urine*; D002853:Chromatography, Liquid; D019587:Dietary Supplements; D018450:Disease Progression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007535:Isomerases / Q000172:deficiency; D008107:Liver Diseases / Q000175:diagnosis / Q000188:drug therapy*; D043202:Steroid Metabolism, Inborn Errors / Q000175:diagnosis / Q000188:drug therapy*; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; C014596:3 beta-hydroxy-delta 5-cholenic acid; D014580:Ursodeoxycholic Acid; D015096:3-Hydroxysteroid Dehydrogenases; D007535:Isomerases