Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome.
We measured plasma sterol concentrations in 7 homozygotes with the Smith-Lemli-Opitz syndrome, 5 heterozygotes and rats treated with BM 15.766, the competitive inhibitor of 7-dehydrocholesterol 7-reductase. Low cholesterol associated with markedly elevated 7-dehydrocholesterol concentrations were detected in the plasma of all homozygotes and inhibitor-treated rats. Heterozygotes were clinically normal and, like control subjects, showed only trace amounts of 7-dehydrocholesterol in plasma. We conclude that the Smith-Lemli-Opitz syndrome is due to an inherited defect in 7 dehydrocholesterol 7-reductase which causes the accumulation of 7-dehydrocholesterol and a deficiency of cholesterol in the plasma, a biochemical abnormality that can be reproduced in rats treated with BM 15.766.
Salen
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Veterans Affairs Medical Center, East Orange, NJ, USA.
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Xu
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Batta
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Elias
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D000293:Adolescent; D000328:Adult; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D003684:Dehydrocholesterols / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008875:Middle Aged; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000172:deficiency; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019082:Smith-Lemli-Opitz Syndrome / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
D000924:Anticholesteremic Agents; D003684:Dehydrocholesterols; D004791:Enzyme Inhibitors; D010879:Piperazines; C047457:BM 15766; D002784:Cholesterol; C016705:7-dehydrocholesterol; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase