| Molecular genetic and bile acid profiles in two Japanese patients with 3beta-hydroxy-DELTA5-C27-steroid dehydrogenase/isomerase deficiency. | |
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MedLine Citation:
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PMID: 20531254 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Case Reports; Journal Article |
Journal Detail:
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Title: Pediatric research Volume: 68 ISSN: 1530-0447 ISO Abbreviation: Pediatr. Res. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-24 Completed Date: 2010-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 258-63 Citation Subset: IM |
Affiliation:
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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 | |
Descriptor/Qualifier:
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3-Hydroxysteroid Dehydrogenases
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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 Humans Infant Infant, Newborn Infant, Newborn, Diseases / diagnosis, drug therapy*, enzymology* Japan Liver / drug effects, physiopathology Male Molecular Sequence Data Mutation / genetics Sequence Analysis, DNA |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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