Document Detail

Molecular genetic and bile acid profiles in two Japanese patients with 3beta-hydroxy-DELTA5-C27-steroid dehydrogenase/isomerase deficiency.
MedLine Citation:
PMID:  20531254     Owner:  NLM     Status:  MEDLINE    
We report definitive diagnosis and effective chenodeoxycholic acid (CDCA) treatment of two Japanese children with 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. Findings of cholestasis with normal serum [gamma]-glutamyltransferase activity and total bile acid concentration indicated the need for definitive bile acid analysis. Large amounts of 3[beta]-hydroxy-[DELTA]5 bile acids were detected by gas chromatography-mass spectrometry. HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patients and their parents identified four novel mutations of the HSD3B7 gene in the patients. One had a homozygous mutation, 314delA; the other had compound heterozygous mutations: V132F, T149I, and 973_974insCCTGC. Interestingly, the second patient's mother had V132F and T149I mutations in one allele. Excessive 3[beta]-hydroxy-[DELTA]5-bile acids such as 3[beta],7[alpha]-dihydroxy- and 3[beta],7[alpha],12[alpha]-trihydroxy-5-cholenoic acids were detected in the first patient's urine; the second patient's urine contained large amounts of 3[beta]-hydroxy-5-cholenoic acid. Liver dysfunction in both patients decreased with ursodeoxycholic acid treatment, but unusual bile acids were still detected. Normalization of the patients' liver function and improvement of bile acid profiles occurred with CDCA treatment. Thus, we found mutations in the HSD3B7 gene accounting for autosomal recessive neonatal cholestasis caused by 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. Early neonatal diagnosis permits initiation of CDCA treatment at this critical time, before the late cholestatic stage.
Tatsuki Mizuochi; Akihiko Kimura; Isao Ueki; Tomoyuki Takahashi; Takuji Hashimoto; Akira Takao; Yoshitaka Seki; Hajime Takei; Hiroshi Nittono; Takao Kurosawa; Toyojiro Matsuishi
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  Pediatric research     Volume:  68     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-24     Completed Date:  2010-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  258-63     Citation Subset:  IM    
Department of Pediatrics and Child Health, Division of Gene Therapy and Regenerative Medicine, Kurume University School of Medicine, Kurume, Japan.
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MeSH Terms
3-Hydroxysteroid Dehydrogenases / deficiency*,  genetics*
Base Sequence
Bile Acids and Salts / urine*
Chenodeoxycholic Acid / pharmacology,  therapeutic use*
Cholestasis / diagnosis,  drug therapy*,  enzymology*
DNA Primers / genetics
Gas Chromatography-Mass Spectrometry
Infant, Newborn
Infant, Newborn, Diseases / diagnosis,  drug therapy*,  enzymology*
Liver / drug effects,  physiopathology
Molecular Sequence Data
Mutation / genetics
Sequence Analysis, DNA
Reg. No./Substance:
0/Bile Acids and Salts; 0/DNA Primers; 474-25-9/Chenodeoxycholic Acid; EC 1.1.-/3-Hydroxysteroid Dehydrogenases; EC 1.1.1.-/3 beta-hydroxy-delta 5-C(27)-steroid dehydrogenase

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