Titration of Bile Acid Supplements in 3 beta-Hydroxy-Delta 5-C27-Steroid Dehydrogenase/Isomerase Deficiency

OBJECTIVES: 3β-Hydroxy-Δ5-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 3β,7α-dihydroxy-5-cholenoic acid (u-3β-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-3β-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-3β-D-OH-5C levels was 5/5 mg • kg-1 • day-1. A follow-up biopsy in 2 patients showed no progression of liver disease. CONCLUSIONS: A mixture of UDCA/CDCA can effectively control 3β-hydroxy-Δ5-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.