Abstract
Smith-Lemli-Opitz syndrome is a condition of impaired cholesterol synthesis that is caused by mutations in DHCR7 encoding 7-dehydrocholesterol-Δ7 reductase. Birth defects and mental retardation are characteristic. Deficient plasma and tissue cholesterol and excess cholesterol precursors 7 and 8 dehydrocholesterol (7DHC and 8DHC) contribute to the pathogenesis. Cholesterol is transported to tissues via lipoproteins. We measured the effect of dietary cholesterol (egg yolk) on plasma lipoproteins to evaluate this potential treatment. We used the enzymatic method to measure total sterols in lipoproteins (n = 12) and plasma (n = 16). In addition, we analyzed individual plasma sterols by a gas chromatographic method. Samples were evaluated after 3 wk of a cholesterol-free diet and after 6–19 mo of dietary cholesterol. We also analyzed the distribution of sterols in lipoproteins and the apolipoprotein E genotype. Dietary cholesterol significantly increased the total sterols in plasma (2.22 ± 0.13 to 3.10 ± 0.22; mean ± SEM; p < 0.002), in LDL (0.98 ± 0.13 to 1.52 ± 0.17 mM), and in HDL (0.72 ± 0.04 to 0.92 ± 0.07). Plasma cholesterol increased (1.78 ± 0.16 to 2.67 ± 0.25 mM; p < 0.007) and plasma 7DHC decreased in 10 children, but the mean decrease was not significant. The distribution of individual sterols in each lipoprotein fraction was similar to the distribution in plasma. The baseline cholesterol and the response to dietary cholesterol was the same in children with 3/3 and 3/4 apolipoprotein E genotypes. Dietary cholesterol increased total sterols in plasma, LDL, and HDL in children with Smith-Lemli-Opitz syndrome. These favorable increases in the lipoproteins are potentially therapeutic for this condition.
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Abbreviations
- apoE:
-
apolipoprotein E
- DHCR7:
-
7-dehydrocholesterol Δ7-reductase
- HMG:
-
hepatic hydroxymethyl glutaryl
- SLOS:
-
Smith-Lemli-Opitz syndrome
- 7DHC:
-
7-dehydrocholesterol
- 8DHC:
-
8-dehydrocholesterol
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Acknowledgements
We thank Gary Sexton, Ph.D., for assistance with statistical analysis and Pam Smith and Carol Marsh for lipoprotein separation. We thank the children and families for participation in the study and the staff of the Oregon Health & Science University General Clinical Research Center. We thank Sandra Banta-Wright, R.N., M.S.N., N.N.P., Daniel Marks, M.D., and numerous other health care providers who assisted in the care of these children. We thank the many health care providers who kindly referred these children to us.
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Supported by grants from the National Heart, Lung, and Blood Institute (PHS HL-64618 and HL-073980); National Center for Research Resources (PHS 5 M01 RR000334 and PHS 3 M01 RR003344-33S3); National Institute for Child Health and Human Development, OR Child Health Research Center (PHS 5P30 HD33703-04); the American Academy of Pediatrics Section on Genetics and Birth Defects; the Collins Foundation; and the Smith-Lemli-Opitz Advocacy and Exchange. R.D.S. is a Clinical Associate Physician Investigator of the Oregon Health & Science University General Clinical Research Center.
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Merkens, L., Connor, W., Linck, L. et al. Effects of Dietary Cholesterol on Plasma Lipoproteins in Smith-Lemli-Opitz Syndrome. Pediatr Res 56, 726–732 (2004). https://doi.org/10.1203/01.PDR.0000141522.14177.4F
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DOI: https://doi.org/10.1203/01.PDR.0000141522.14177.4F
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