Lm. Linck et al., Cholesterol supplementation with egg yolk increases plasma cholesterol anddecreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome, AM J MED G, 93(5), 2000, pp. 360-365
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.