Neonatal cholestasis with increased 3β-monohydroxy-Δ5 bile acids in serum and urine: Not necessarily primary oxysterol 7α hydroxylase deficiency

Background: Inborn errors of bile acid synthesis are rare genetic disorders that can present with cholestatic liver disease. Recently we encountered 3 infants with neonatal cholestasis and excessive 3 beta-monohydroxy-Delta(5)-C-24 bile acids in serum and urine. We investigated whether identification of 3 beta-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol in serum and urine of cholestatic patients is necessary for diagnosis of primary oxysterol 7 alpha-hydroxylase deficiency. Methods: These 3 patients initially led us to suspected oxysterol 7 alpha-hydroxylase deficiency. However, sequence analysis of genomic DNA resulted in diagnosis of 2 patients with oxysterol 7 alpha-hydroxylase deficiency and 1 patient with 3 beta-hydroxy-Delta(5)-C-27-steroid dehydrogenase/isomerase deficiency. We examined identification of 3 beta-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol by gas chromatography-mass spectrometry after diagnosis. Results: Interestingly, we detected a peak for 3 beta-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol of the neutral sterol in urine from 2 patients who were diagnosed with primary oxysterol 7 alpha-hydroxylase deficiency. Conclusion: In evaluating infants with cholestasis and excessive 3 beta-monohydroxy-Delta(5)-C-24 bile acids in infancy, one needs to conduct C-24 bile acid analysis serially. Results can guide performance and interpretation of genomic DNA analysis. Moreover, identification of 3 beta-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol in urine is highly important for diagnosis of oxysterol 7 alpha-hydroxylase deficiency as is genomic DNA analysis. (C) 2012 Elsevier B.V. All rights reserved.