Neonatal cholestasis with increased 3¦Â-monohydroxy-¦¤⁵ bile acids in serum and urine: Not necessarily primary oxysterol 7¦Á hydroxylase deficiency

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• 作者：Akihiko Kimura ; Hiroshi Nittono ; Tatsuki Mizuochi ; Isao Ueki ; Takao Kurosawa ; Akina Muto ; Hajime Takei
• 关键词：CYP7B1 ; oxysterol 7¦Á-hydroxylase ; HSD3B7 ; 3¦Â-hydroxy-¦¤5-C27-steroid dehydrogenase/isomerase ; CYP7A1 ; cholesterol 7¦Á-hydroxylase ; AST ; aspartate aminotransferase ; ALT ; alanine aminotransferase ; ¦Ã-GTT ; ¦Ã-glutaryl transpeptidase ; UDCA ; ursodeoxycholic
• 刊名：Clinica Chimica Acta
• 出版年：2012
• 出版时间：9 October, 2012
• 年：2012
• 卷：413
• 期：19-20
• 页码：1700-1704
• 全文大小：449 K

文摘

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¦Â-monohydroxy-¦¤⁵-C₂₄ bile acids in serum and urine. We investigated whether identification of 3¦Â-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol in serum and urine of cholestatic patients is necessary for diagnosis of primary oxysterol 7¦Á-hydroxylase deficiency.

Methods

These 3 patients initially led us to suspected oxysterol 7¦Á-hydroxylase deficiency. However, sequence analysis of genomic DNA resulted in diagnosis of 2 patients with oxysterol 7¦Á-hydroxylase deficiency and 1 patient with 3¦Â-hydroxy-¦¤⁵-C₂₇-steroid dehydrogenase/isomerase deficiency. We examined identification of 3¦Â-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol by gas chromatography-mass spectrometry after diagnosis.

Results

Interestingly, we detected a peak for 3¦Â-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¦Á-hydroxylase deficiency.

Conclusion

In evaluating infants with cholestasis and excessive 3¦Â-monohydroxy-¦¤⁵-C₂₄ bile acids in infancy, one needs to conduct C₂₄ bile acid analysis serially. Results can guide performance and interpretation of genomic DNA analysis. Moreover, identification of 3¦Â-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol in urine is highly important for diagnosis of oxysterol 7¦Á-hydroxylase deficiency as is genomic DNA analysis.