Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by a defect in cholesterol metabolism. Affected individuals have deficiency in the final enzyme in cholesterol synthesis, 7-dehydrocholesterol-delta-7-reductase. As a result, cholesterol levels are low and 7-dehydrocholesterol (7-DHC) levels are elevated. 7-DHC may cause learning problems in a rat model of SLOS (Xu et. al., 1998). There are also anecdotal reports of improved behavior and development in SLOS subjects provided with cholesterol supplements. (Elias et. al., 1997). We hypothesized that cholesterol supplementation would improve the developmental progress of children with SLOS by ameliorating cholesterol deficiency and/or inhibiting 7-DHC synthesis by feedback inhibition. Seven children with Smith-Lemli-Opitz syndrome participated in a research protocol where whole body cholesterol synthesis was measured by the sterol balance technique. Baseline developmental evaluation was performed by the Bailey examination in 6 subjects, and by the Peabody Scales of Motor Development in one. After the original evaluation, subjects were provided a diet supplemented in cholesterol (1-2 hard boiled egg yolks dairy). Developmental evaluations were performed at baseline and again after cholesterol supplementation. The longest duration of cholesterol supplementation at the time of reassessment was 31 months. Five of the patients began cholesterol supplementation before 6 months of age. All of the children are exhibiting delays in mental development, while all but one show delays in motor development. The scores for the mental development were all less than or equal to 57, and all of the motor scores were less than 50, with the exception of one child in the normal range (128). The subject assessed by the Peabody was also significantly delayed in motor skills. None has had a significant improvement in developmental progress, despite early and nearly continuous cholesterol supplementation. Several of the subjects parents reported sleep difficulties and increased agitation during 3 week intervals of cholesterol supplementation. If treatment for SLOS is to be effective, it may need to begin prenatally, and/or efforts may need to be made to allow cholesterol to cross the blood-brain barrier.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Feb 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)