Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome.
Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition comprising multiple malformations, mental retardation, and growth failure, results from reduced activity of the final enzyme in cholesterol biosynthesis, 7-dehydrocholesterol Delta(7)-reductase (DHCR7). Reduced plasma and tissue cholesterol concentrations and accumulation of cholesterol precursors including 7-dehydrocholesterol (7-DHC) are characteristic biochemical abnormalities. While it is still unclear what role these potentially toxic precursors have in the pathogenesis of this disorder, the accumulation of 7-DHC in the brain has been associated with impaired learning in rats and oxidized 7-DHC has been shown to induce growth retardation in cultured rat embryos. We hypothesized that supplemental dietary cholesterol would increase plasma cholesterol levels and suppress synthesis of 7-DHC and other abnormal sterols in individuals with SLOS. After baseline sterol levels were obtained, patients were provided supplemental cholesterol as egg yolk. Plasma sterols were analyzed by capillary-column gas chromatography over time in four children with SLOS. When evaluated at 4-8 weeks after the initiation of cholesterol supplementation, there was a marked increase in mean plasma cholesterol, from 53 mg/dl to 82 mg/dl. While the percent of total sterols as 7-DHC decreased from 15% to 10%, there was no change in total plasma 7-DHC levels. However, when evaluated 35-90 weeks after the institution of cholesterol supplementation, mean plasma 7-DHC decreased, from 11.3 mg/dl to 3.5 mg/dl (-67%, P < 0.05), along with an increase in mean plasma cholesterol from 53 mg/dl to 114 mg/dl (+116%, P < 0.05). These results support the hypothesis that over time dietary cholesterol supplementation from egg yolk increases the plasma cholesterol levels and decreases levels of 7-DHC which may be toxic. These data have important therapeutic implications in the management of SLOS.
Linck
L M
LM
Department of Pediatrics and Department of Molecular and Medical Genetics, Child Development and Rehabilitation Center, Doernbecher Children's Hospital, Oregon Health Sciences University, Portland, Oregon, USA.
Lin
D S
DS
Flavell
D
D
Connor
W E
WE
Steiner
R D
RD
D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D003684:Dehydrocholesterols / Q000097:blood*; D004530:Egg Yolk / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D019082:Smith-Lemli-Opitz Syndrome / Q000097:blood / Q000378:metabolism / Q000628:therapy*
D002791:Cholesterol, Dietary; D003684:Dehydrocholesterols; D002784:Cholesterol; C016705:7-dehydrocholesterol