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Published on: November 27, 2016
Titration of bile acid supplements in 3beta-hydroxy-Delta 5-C27-steroid dehydrogenase/isomerase deficiency
L Riello1, L D'Antiga, M Guido
1Department of Paediatrics, Paediatric Liver, University of Padova, Italy.
Objectives:
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.
Patients And 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.
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