HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Steiner, R. D. Articles by Connor, W. E. Search for Related Content PubMed PubMed Citation Articles by Steiner, R. D. Articles by Connor, W. E. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 1437-1447, September 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Sterol balance in the Smith-Lemli-Opitz syndrome: reduction in whole body cholesterol synthesis and normal bile acid production

Correspondence to: Robert D. Steiner

The Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by a deficiency of the enzyme 7-dehydrocholesterol 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.—Steiner, R. D., L. M. Linck, D. P. Flavell, D. S. Lin, and W. E. Connor. Sterol balance in the Smith-Lemli-Opitz syndrome: reduction in whole body cholesterol synthesis and normal bile acid production. J. Lipid Res. 2000. 41: 1437;–1447.

Supplementary key words: hypocholesterolemia, multiple malformations, sterols, 7-dehydrocholesterol, 8-dehydrocholesterol, gas chromatography, metabolism of sterols, plant sterols, bacterial modification of sterols

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. B. Patel and R. D. Steiner In Memoriam: William E. Connor (1921-2009) J. Lipid Res., April 1, 2010; 51(4): 679 - 681. [Full Text] [PDF]

				A. S. Pappu, W. E. Connor, L. S. Merkens, J. M. Jordan, J. A. Penfield, D. R. Illingworth, and R. D. Steiner Increased nonsterol isoprenoids, dolichol and ubiquinone, in the Smith-Lemli-Opitz syndrome: effects of dietary cholesterol J. Lipid Res., December 1, 2006; 47(12): 2789 - 2798. [Abstract] [Full Text] [PDF]

				W. E. Connor, Y. Wang, M. Green, and D. S. Lin Effects of diet and metamorphosis upon the sterol composition of the butterfly Morpho peleides J. Lipid Res., July 1, 2006; 47(7): 1444 - 1448. [Abstract] [Full Text] [PDF]

				R. P. Koldamova, I. M. Lefterov, M. D. Ikonomovic, J. Skoko, P. I. Lefterov, B. A. Isanski, S. T. DeKosky, and J. S. Lazo 22R-Hydroxycholesterol and 9-cis-Retinoic Acid Induce ATP-binding Cassette Transporter A1 Expression and Cholesterol Efflux in Brain Cells and Decrease Amyloid beta Secretion J. Biol. Chem., April 4, 2003; 278(15): 13244 - 13256. [Abstract] [Full Text] [PDF]

				G. E. Herman Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes Hum. Mol. Genet., April 2, 2003; 12(90001): R75 - 88. [Abstract] [Full Text] [PDF]

				A. S. Pappu, R. D. Steiner, S. L. Connor, D. P. Flavell, D. S. Lin, L. Hatcher, D. R. Illingworth, and W. E. Connor Feedback inhibition of the cholesterol biosynthetic pathway in patients with Smith-Lemli-Opitz syndrome as demonstrated by urinary mevalonate excretion J. Lipid Res., October 1, 2002; 43(10): 1661 - 1669. [Abstract] [Full Text] [PDF]

				B. Ruan, W. K. Wilson, J. Pang, N. Gerst, F. D. Pinkerton, J. Tsai, R. I. Kelley, F. G. Whitby, D. M. Milewicz, J. Garbern, et al. Sterols in blood of normal and Smith-Lemli-Opitz subjects J. Lipid Res., May 1, 2001; 42(5): 799 - 812. [Abstract] [Full Text]