Document Detail


Sterol balance in the Smith-Lemli-Opitz syndrome. Reduction in whole body cholesterol synthesis and normal bile acid production.
MedLine Citation:
PMID:  10974051     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by a deficiency of the enzyme 7-dehydrocholesterol Delta(7)-reductase. This enzyme converts 7-dehydrocholesterol (7-DHC) to cholesterol in the last step in cholesterol biosynthesis. The pathology of this condition may result from two different factors: the deficiency of cholesterol itself and/or the accumulation of precursor sterols such as 7-DHC. Although cholesterol synthesis is defective in cultured SLOS cells, to date there has been no evidence of decreased whole body cholesterol synthesis in SLOS and only incomplete information on the synthesis of 7-DHC and bile acids. In this first report of the sterol balance in SLOS, we measured the synthesis of cholesterol, other sterols, and bile acids in eight SLOS subjects and six normal children. The diets were very low in cholesterol content and precisely controlled. Cholesterol synthesis in SLOS subjects was significantly reduced when compared with control subjects (8.6 vs. 19.6 mg/kg per day, respectively, P < 0.002). Cholesterol precursors 7-DHC, 8-DHC, and 19-nor-cholestatrienol were synthesized in SLOS subjects (7-DHC synthesis was 1.66 +/- 1.15 mg/kg per day), but not in control subjects. Total sterol synthesis was also reduced in SLOS subjects (12 vs. 20 mg/kg per day, P < 0.022). Bile acid synthesis in SLOS subjects (3.5 mg/kg per day) did not differ significantly from control subjects (4.6 mg/kg per day) and was within the range reported previously in normals. Normal primary and secondary bile acids were identified. This study provides direct evidence that whole body cholesterol synthesis is reduced in patients with SLOS and that the synthesis of 7-DHC and other cholesterol precursors is profoundly increased. It is also the first reported measure of daily bile acid synthesis in SLOS and provides evidence that bile acid supplementation is not likely to be necessary for treatment. These sterol balance studies provide basic information about the biochemical defect in SLOS and strengthen the rationale for the use of dietary cholesterol in its treatment.
Authors:
R D Steiner; L M Linck; D P Flavell; D S Lin; W E Connor
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of lipid research     Volume:  41     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-11-24     Completed Date:  2000-11-24     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1437-47     Citation Subset:  IM    
Affiliation:
Departments of Pediatrics and Molecular and Medical Genetics, Child Development and Rehabilitation Center, Doernbecher Children's Hospital, Portland, OR 97201, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Bile Acids and Salts / metabolism*
Child, Preschool
Cholesterol / metabolism*
Cholesterol, Dietary
Female
Humans
Infant
Male
Reference Values
Smith-Lemli-Opitz Syndrome / blood,  metabolism*
Sterols / blood*
Grant Support
ID/Acronym/Agency:
HD 33703-03/HD/NICHD NIH HHS; HL64618/HL/NHLBI NIH HHS; M01 RR00334-33S3/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholesterol, Dietary; 0/Sterols; 57-88-5/Cholesterol

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