Abstract
The Smith-Lemli-Opitz syndrome (SLOS) is a disorder of impaired cholesterol biosynthesis because of a deficiency of the enzyme 7-dehydrocholesterol-Δ7-reductase, in the last step in cholesterol biosynthesis. Dietary cholesterol has been proposed as a potential therapy for SLOS and is being tested currently. Because there is no information on cholesterol absorption in SLOS, we recruited 12 SLOS patients into the General Clinical Research Center for 1-wk periods for administration of test meals and for blood and stool collections. A test breakfast that contained tracer cholesterol-4-C14 with egg yolk or with crystalline cholesterol in suspension was given subsequently. Twenty-four and 48-h blood and 1-wk stool samples then were collected. The radioactivities in these samples were analyzed to determine the absorption of cholesterol by these patients. In 11 patients who were given egg yolk cholesterol, cholesterol absorption was 27.3 ± 6.7%. The absorption was slightly less at 20.5 ± 10.3% but not significantly different for the six patients who were given crystalline cholesterol. There was a positive correlation between the absorption of isotopic cholesterol as measured by determination of radioactive cholesterol in stool and the amount of isotopic cholesterol in the plasma at 24 and 48 h after the meal. Our data indicated that SLOS patients absorb cholesterol from the diet. However, the percentage of absorption is lower than reported values for normal adults and for hypercholesterolemic children. The absorption of crystalline cholesterol in suspension was slightly lower than the absorption of cholesterol in egg yolk cholesterol by these patients. The absorption of cholesterol may ameliorate some of the biochemical and developmental deficits in SLOS patients.
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Abbreviations
- GCRC:
-
General Clinical Research Center
- SLOS:
-
Smith-Lemli-Opitz syndrome
- 7-DHC:
-
7-dehydrocholesterol
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Acknowledgements
We thank the staff of the OHSU GCRC. We thank all health care providers who assisted in the care of these patients and for subject referrals to us. We thank Drs. Leesa Linck and Dan Marks for expert assistance with care of research subjects. We thank the children and their families for participation in this study.
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This project was supported by grants from the National Heart, Lung, and Blood Institute (HL64618 and HL 073981) and by a grant from the American Academy of Pediatrics Section on Genetics and Birth Defects and by a General Clinical Research Center grant (PHS M01-RR000334). R.D.S. is a Clinical Associate Physician of the General Clinical Research Centers (PHS M01-RR000334-33S3). We also acknowledge support from the Collins Foundation and the Smith-Lemli-Opitz Advocacy and Exchange and the Oregon Child Health Research Center (National Institute of Child Health and Human Development, PHS P30-HD33703-04).
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Lin, D., Steiner, R., Flavell, D. et al. Intestinal Absorption of Cholesterol by Patients with Smith-Lemli-Opitz Syndrome. Pediatr Res 57, 765–770 (2005). https://doi.org/10.1203/01.PDR.0000157723.98422.B5
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DOI: https://doi.org/10.1203/01.PDR.0000157723.98422.B5
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