Abstract

The Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by a deficiency of the enzyme 7 dehydrocholesterol Δ7-reductase. This enzyme converts 7-dehydrocholesterol (7-DHC) to cholesterol in the last step in cholesterol biosynthesis. The pathology of this condition may result from two different factors: the deficiency of cholesterol itself and/or the accumulation of precursor sterols such as 7-DHC. Although cholesterol synthesis is defective in cultured SLOS cells, to date there has been no evidence of decreased whole body cholesterol synthesis in SLOS and only incomplete information on the synthesis of 7-DHC and bile acids. In this first report of the sterol balance in SLOS, we measured the synthesis of cholesterol, other sterols, and bile acids in eight SLOS subjects and six normal children. The diets were very low in cholesterol content and precisely controlled. Cholesterol synthesis in SLOS subjects was significantly reduced when compared with control subjects (8.6 vs. 19.6 mg/kg per day, respectively, P < 0.002).