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 3β-monohydroxy-Δ⁵-C₂₄ 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-Δ⁵-C₂₇-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.


CONCLUSIONS
In evaluating infants with cholestasis and excessive 3β-monohydroxy-Δ⁵-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 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.
Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan. hirof@med.kurume-u.ac.jp
Akihiko
A
Kimura
Hiroshi
H
Nittono
Tatsuki
T
Mizuochi
Isao
I
Ueki
Takao
T
Kurosawa
Akina
A
Muto
Hajime
H
Takei
D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D044466:Asian People; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000097:blood* / Q000652:urine*; D002779:Cholestasis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006888:Hydroxycholesterols / Q000652:urine; D007223:Infant; D007535:Isomerases / Q000172:deficiency* / Q000235:genetics; D008297:Male; D017422:Sequence Analysis, DNA; D013250:Steroid Hydroxylases / Q000172:deficiency* / Q000235:genetics
D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; C076996:27-hydroxycholesterol; D004247:DNA; D015096:3-Hydroxysteroid Dehydrogenases; C066485:3 beta-hydroxy-delta 5-C(27)-steroid dehydrogenase; D013250:Steroid Hydroxylases; C115867:oxysterol 7-alpha-hydroxylase; D007535:Isomerases