Titration of bile acid supplements in 3beta-hydroxy-Delta 5-C27-steroid dehydrogenase/isomerase deficiency.

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.

Effects of different formula feeds on the developmental pattern of urinary bile acid excretion in infants.

The excretion of bile acids in urine was followed prospectively during the first year of life in 17 infants fed different diets from the age of 3 to 10 days. Eight infants were breast-fed, four were fed formulas that were based on adapted cow's milk, and five were fed a formula that was based on soy protein isolate. The formulas had higher protein concentrations than human milk; had different types of proteins, and had not been supplemented with taurine. Urinary bile acids were determined by gas-liquid chromatographic/mass spectrometric analyses of 24-h urinary samples collected at 1-12 days (only formula-fed infants) and at 1, 3, 6, 9, and 12 months of age. The results showed a higher urinary bile acid excretion at 3 months of age in both formula groups than in the breast-fed infants. A deficiency of dietary taurine during formula-feeding did not seem to limit the formation of taurine conjugates during the first month of life. The developmental pattern of urinary bile acid excretion during the first year differed according to the type of feeding. Isomers of cholic and chenodeoxycholic acid appeared in the urine of all breast-fed infants at 6 to 12 months of age. These metabolites, assumed to be the first metabolites derived from the developing gut flora of the infants, appeared at an earlier age and in higher amounts in both formula groups compared to breast-fed infants. Bile acids lacking a 7-hydroxy group, known to be formed by the intestinal flora, appeared in infants in all feeding groups later than the isomers. The results of the study imply that the early introduction of formula may modify bile acid metabolism in infants.

Effect of phototherapy on the physiologic cholestasis of the neonate.

Phototherapy (PT) has been reported to increase bile acid excretion in the bile of adults with liver cirrhosis. We investigated the effect of PT on the levels of serum total bile acids (STBA), conjugated cholic acid (CCA), conjugated chenodeoxycholic acid (CCDCA), conjugated lithocholic acid (CLCA), and sulfolithocholylglycine (SLCG) in 13 neonates with unconjugated nonhemolytic hyperbilirubinemia before and after 12 h of PT. The treatment produced a statistically significant (p less than 0.02) reduction in both STBA and CCA levels, whereas no effect on the other fractions was observed. The percentage of reduction was the same for STBA and CCA concentrations, indicating that the effect is related to a specific reduction in CCA levels. The magnitude of the expected decrease in the level of serum bilirubin is not correlated with that in bile acids in individual cases. The data are interpreted as suggesting that PT can affect the metabolism of bile acids by decreasing STBA and CCA levels in neonates through an increase in their biliary excretion associated with the reduced intestinal absorption of CCA occurring in newborns.