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

Abstract 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 3β-monohydroxy-Δ 5 -C 24 bile acids in serum and urine. We investigated whether identification of 3β-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol in serum and urine of cholestatic patients is necessary for diagnosis of primary oxysterol 7α-hydroxylase deficiency. Methods These 3 patients initially led us to suspected oxysterol 7α-hydroxylase deficiency. However, sequence analysis of genomic DNA resulted in diagnosis of 2 patients with oxysterol 7α-hydroxylase deficiency and 1 patient with 3β-hydroxy-Δ 5 -C 27 -steroid dehydrogenase/isomerase deficiency. We examined identification of 3β-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol by gas chromatography–mass spectrometry after diagnosis. Results Interestingly, we detected a peak for 3β-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol of the neutral sterol in urine from 2 patients who were diagnosed with primary oxysterol 7α-hydroxylase deficiency. Conclusion In evaluating infants with cholestasis and excessive 3β-monohydroxy-Δ 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 3β-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol in urine is highly important for diagnosis of oxysterol 7α-hydroxylase deficiency as is genomic DNA analysis.