Cholesterol supplementation with egg yolk increases plasma cholesterol anddecreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition compris ing multiple malformations, mental retardation, and growth failure, results from reduced activity of the final enzyme in cholesterol biosynthesis, 7-d ehydrocholesterol Delta(7)-reductase (DHCR7), Reduced plasma and tissue cho lesterol concentrations and accumulation of cholesterol precursors includin g 7-dehydrocholesterol (7-DHC) are characteristic biochemical abnormalities . While it is still unclear what role these potentially toxic precursors ha ve in the pathogenesis of this disorder, the accumulation of 7-DHC in the b rain has been associated with impaired learning in rats and oxidized 7-DHC has been shown to induce growth retardation in cultured rat embryos. We hyp othesized that supplemental dietary cholesterol would increase plasma chole sterol levels and suppress synthesis of 7-DHC and other abnormal sterols in individuals with SLOS. After baseline sterol levels were obtained, patient s were provided supplemental cholesterol as egg yolk. Plasma sterols were a nalyzed by capillary-column gas chromatography over time in four children w ith SLOS, When evaluated at 4-8 weeks after the initiation of cholesterol s upplementation, there was a marked increase in mean plasma cholesterol, fro m 53 mg/dl to 82 mg/dl, While the percent of total sterols as 7-DHC decreas ed from 15% to 10%, there was no change in total plasma 7-DHC levels. Howev er, when evaluated 35-90 weeks after the institution of cholesterol supplem entation, 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 o ver time dietary cholesterol supplementation from egg yolk increases the pl asma cholesterol levels and decreases levels of 7-DHC which may be toxic. T hese data have important therapeutic implications in the management of SLOS , (C) 2000 Wiley-Liss, Inc.