Intestinal absorption of cholesterol by patients with Smith-Lemli-Opitz syndrome

The Smith-Lemli-Opitz syndrome (SLOS) is a disorder of impaired cholesterol biosynthesis because of a deficiency of the enzyme 7-dehydrocholesterol-Delta(7)-reductase, in the last step in cholesterol biosynthesis. Dietary cholesterol has been proposed as a potential therapy for SLOS and is being tested currently. Because there is no information on cholesterol absorption in SLOS, we recruited 12 SLOS patients into the General Clinical Research Center for 1-wk periods for administration of test meals and for blood and stool collections. A test breakfast that contained tracer cholesterol-4-C(14) with egg yolk or with crystalline cholesterol in suspension was given subsequently. Twenty-four and 48-h blood and 1-wk stool samples then were collected. The radioactivities in these samples were analyzed to determine the absorption of cholesterol by these patients. In 11 patients who were given egg yolk cholesterol, cholesterol absorption was 27.3 +/- 6.7%. The absorption was slightly less at 20.5 +/- 10.3% but not significantly different for the six patients who were given crystalline cholesterol. There was a positive correlation between the absorption of isotopic cholesterol as measured by determination of radioactive cholesterol in stool and the amount of isotopic cholesterol in the plasma at 24 and 48 h after the meal. Our data indicated that SLOS patients absorb cholesterol from the diet. However, the percentage of absorption is lower than reported values for normal adults and for hypercholesterolemic children. The absorption of crystalline cholesterol in suspension was slightly lower than the absorption of cholesterol in egg yolk cholesterol by these patients. The absorption of cholesterol may ameliorate some of the biochemical and developmental deficits in SLOS patients.